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Where our analysis comes from

The source hierarchy our analysis follows — peer-reviewed pharmacology first, regulators as legal context.

Regimens™ evaluates everything you take — medications, supplements, herbs, foods, peptides, recreational substances — and flags interactions, contraindications, timing conflicts, and depletion patterns. The quality of that analysis is only as good as its sources.

This page exists because most AI wellness tools won’t tell you where their information comes from, and we think you deserve to know.

01.

Our principle: science first, regulation as context

When peer-reviewed pharmacology research and a national regulator’s position diverge, we lead with the science.

National regulators like the FDA, DEA, MHRA, and EMA serve essential functions — they manage legal status, approve indications, and protect public safety. But regulatory frameworks lag the scientific literature, sometimes by decades. The 2002 FDA consumer advisory on kava, for example, persists in the regulatory record despite subsequent research substantially reframing those original case reports — and despite the 2020 Codex Alimentarius standard that recognizes traditionally prepared aqueous kava as a food.

When MDMA-assisted therapy showed Phase 3 efficacy for PTSD in 2021, the DEA’s Schedule I designation didn’t move. The science had advanced; the regulatory framework hadn’t.

Citing regulatory bodies as the primary scientific authority would mean accepting that latency as truth. We don’t.

Instead, our analysis follows a tiered hierarchy that prioritizes the underlying evidence and treats regulatory positions as legal-status context.

02.

The source hierarchy

The tiers below are the universe of evidence the analyzer is built to reason within. Tier 1 leads; each lower tier is cited for what it is authoritative on, not as a substitute for stronger evidence. National regulators close the hierarchy at Tier 6 as legal context, not scientific authority.

Tier 1 — Peer-reviewed pharmacology and clinical research

This is where the science actually lives. Our analysis prioritizes:

PubMed-indexed primary research

Specifically randomized controlled trials, systematic reviews, and meta-analyses from journals indexed in MEDLINE.

pubmed.ncbi.nlm.nih.gov →

Cochrane systematic reviews

Cochrane is the gold standard for evidence synthesis in medicine — independent, methodologically rigorous, and updated continuously. The Cochrane Complementary Medicine field publishes systematic reviews on integrative and complementary modalities under the same methodological standards.

cochrane.org →

Established pharmacology references

Goodman & Gilman’s The Pharmacological Basis of Therapeutics, Stockley’s Drug Interactions, and other clinical references that practicing pharmacologists actually use.

Preprint servers (bioRxiv, medRxiv)

When relevant emerging research hasn't yet completed peer review, we reference it explicitly as preliminary — not as established consensus.

DrugBank

A comprehensive online drug knowledgebase maintained by the University of Alberta and the Metabolomics Innovation Centre, combining pharmacological, chemical, and target data with peer-reviewed releases through Nucleic Acids Research. The referential drug data source for PharmGKB, KEGG, PubChem, and other major databases.

go.drugbank.com →

IUPHAR/BPS Guide to Pharmacology

Joint resource of the International Union of Basic and Clinical Pharmacology and the British Pharmacological Society. Peer-reviewed overviews of drug targets, ligands, and receptor pharmacology — the authoritative target-level reference for mechanism claims.

guidetopharmacology.org →

Within the peer-reviewed literature, certain journals anchor specific domains. The Tier 1 evidence base frequently draws on journals such as:

Clinical and pharmacology

New England Journal of Medicine

The Lancet

JAMA (Journal of the American Medical Association)

BMJ (British Medical Journal)

Annals of Internal Medicine

Clinical Pharmacology & Therapeutics

British Journal of Clinical Pharmacology

Annals of Pharmacotherapy

Phytotherapy and natural products

Journal of Ethnopharmacology

Phytomedicine

Planta Medica

Phytotherapy Research

Journal of Natural Products

Fitoterapia

Nutrition

American Journal of Clinical Nutrition

Journal of Nutrition

Advances in Nutrition

British Journal of Nutrition

Regional and traditional medicine research

Chinese Medical Journal

Journal of Ayurveda and Integrative Medicine

Journal of Traditional and Complementary Medicine

Tier 1.5 — Clinical practice consensus

Where specialty-clinician consensus runs ahead of formal RCT evidence — peptide therapy, hormone optimization, specialty pharmacology — the practice literature documents the consensus position rigorously. Distinct from Tier 4: T1.5 is direct specialty-clinician consensus in fields where RCTs are structurally limited; T4 is third-party synthesis evaluating evidence with conventional clinical-evidence frameworks.

Peptide protocol literature

Specialty clinical reference texts and society consensus documents covering peptide therapy protocols where regulatory and economic barriers structurally limit RCT evidence.

Specialty-society practice guidelines

Clinical practice guidelines from specialty societies (e.g., Endocrine Society, NAMS, AACE) documenting consensus positions where practice-based knowledge precedes or substitutes for formal RCT evidence.

Specialty pharmacology consensus

Consensus documents from specialty clinical pharmacists addressing dosing, compounding, and protocol questions outside the standard pharmacopoeia.

Practice-specialty reference texts

Reference works documenting specialty practice consensus for compounds and protocols where conventional pharmacology references don't extend.

Tier 2 — Global scientific consensus bodies

Synthesis bodies that aggregate Tier 1 research into globally-coordinated positions.

WHO Expert Committees

Specifically the Expert Committee on Drug Dependence (controlled substances), the Expert Committee on the Selection and Use of Essential Medicines, the Expert Committee on Specifications for Pharmaceutical Preparations, and the Expert Committee on Biological Standardization.

who.int →

Codex Alimentarius (FAO/WHO)

The international food standards body. Codex CXS 336R-2020, for example, is the current standard for kava as a food; we cite it where relevant.

fao.org →

NIH Office of Dietary Supplements (ODS)

For supplement safety, dosing, and interaction information. NIH ODS publishes fact sheets that synthesize the peer-reviewed literature on common supplements.

ods.od.nih.gov →

Endocrine Society Clinical Practice Guidelines

For hormone- and peptide-related compounds.

endocrine.org →

WHO Traditional Medicine Strategy

The WHO framework for evaluating traditional medicine systems against scientific and quality standards. Distinct from but informing the WHO Monographs program.

who.int →

National Academy of Medicine (NAM)

Formerly the Institute of Medicine. Authoritative US synthesis body for clinical and population-health evidence; non-regulatory.

nam.edu →

Dietary Reference Intakes (Food and Nutrition Board, National Academies)

The reference standard for nutrient intake recommendations across North America. Updated by the National Academies' Food and Nutrition Board.

nationalacademies.org →

MedlinePlus (NLM)

Consumer-health synthesis from the National Library of Medicine, drawing from peer-reviewed primary sources. Useful for accessible synthesis of established findings.

medlineplus.gov →

Linus Pauling Institute Micronutrient Information Center

Academic synthesis on vitamins, minerals, and dietary phytochemicals from Oregon State University. Peer-reviewed, free public access — the most rigorous open-access micronutrient reference.

lpi.oregonstate.edu →

European Food Safety Authority (EFSA)

The EU's scientific advisory body for food and feed safety. Issues opinions on novel foods, food additives, contaminants, and nutrient/health claims.

efsa.europa.eu →

USDA FoodData Central

The USDA's authoritative food composition database, public domain. Foundation for most food-composition research globally; the food-compound equivalent of what DrugBank is for drugs.

fdc.nal.usda.gov →

Phenol-Explorer

Comprehensive polyphenol content database maintained by INRAE (France). The standard reference for polyphenol concentrations in foods — directly relevant to plant-compound claims.

phenol-explorer.eu →

EuroFIR eBASIS (Bioactive Substances in Food Information System)

The European bioactive-compound database under the European Food Information Resource consortium. Complements USDA FoodData Central with broader bioactive coverage.

eurofir.org →

USP Herbal Medicines Compendium and Dietary Supplement Verification Program

United States Pharmacopeia's standards for herbal product and dietary supplement identity, purity, strength, and quality. The pharmacopeial reference for supplement integrity.

usp.org →

Tier 3 — Specialized pharmacology references

For specific claim types where dedicated reference works are the standard:

Drug-induced nutrient depletion

Pelton’s Drug-Induced Nutrient Depletion Handbook, Cass’s Supplement Your Prescription, and the broader integrative medicine literature on medication-nutrient interactions.

Pharmacology mechanism

Goodman & Gilman as the primary reference; Katzung’s Basic & Clinical Pharmacology as secondary.

Drug interactions

Stockley’s Drug Interactions (Pharmaceutical Press), the Hansten and Horn Drug Interactions Analysis & Management reference.

Lactation safety

The NLM LactMed database (peer-reviewed, regularly updated).

ncbi.nlm.nih.gov →

Herb-drug interactions

Stockley’s Herbal Medicines Interactions (Williamson, Driver, Baxter, Pharmaceutical Press) — companion volume to Stockley’s Drug Interactions, the primary reference for herb-drug interaction claims.

Pharmacogenomics

PharmGKB (Stanford / NIH-funded Pharmacogenomics Knowledgebase) and the Clinical Pharmacogenetics Implementation Consortium (CPIC), which publishes peer-reviewed gene-drug prescribing guidelines in Clinical Pharmacology & Therapeutics. Cited where pharmacogenomic context affects drug response.

pharmgkb.org →

Clinical reference

Merck Manual Professional Edition (MSD Manual) — broad clinical reference for differential diagnostic and therapeutic context. Freely accessible.

merckmanuals.com →

Tier 4 — Integrative medicine evidence synthesis

Bodies that aggregate peer-reviewed evidence on integrative and complementary modalities, evaluating them with conventional evidentiary standards. Distinct from traditional medicine literature in Tier 5: integrative synthesis bodies use modern clinical-evidence frameworks; traditional pharmacopoeias preserve evidence in a different epistemic register.

National Center for Complementary & Integrative Health (NCCIH, NIH)

The NIH agency funding and synthesizing research on complementary and integrative health practices. Publishes evidence summaries, fact sheets, and clinical research findings.

nccih.nih.gov →

Memorial Sloan Kettering Integrative Medicine — About Herbs

MSK's clinician-facing herb database, peer-reviewed by the institution's oncology and pharmacy services. Authoritative for herb-drug interaction concerns in oncology and clinical care contexts.

mskcc.org →

Natural Medicines Comprehensive Database

The Therapeutic Research Center's clinician-grade evidence database for natural products. Widely used by pharmacists and integrative practitioners for evidence-graded efficacy and interaction information.

naturalmedicines.therapeuticresearch.com →

European Scientific Cooperative on Phytotherapy (ESCOP) Monographs

Sixty-plus monographs harmonizing phytotherapy standards across Europe. Unlike Commission E, ESCOP monographs include explicit references — the European reference for evidence-based phytotherapy.

escop.com →

American Herbal Pharmacopoeia (AHP) Monographs and Therapeutic Compendia

Peer-reviewed by an international multi-disciplinary collective (botanists, chemists, herbalists, pharmacists, pharmacologists, physicians, toxicologists). Each monograph runs roughly thirty pages on a single botanical, integrating quality control, pharmacology, and therapeutic use.

herbal-ahp.org →

WHO Monographs on Selected Medicinal Plants

World Health Organization global synthesis of clinical and traditional evidence on plant medicines. Each monograph applies modern evidentiary frameworks — clinical pharmacology, controlled trial summaries, contraindications, adverse effects — to traditional materia medica. Distinct from the WHO TCM Monographs in Tier 5 (which focus specifically on Traditional Chinese Medicine in the traditional register).

who.int →

American Botanical Council / HerbalGram

Peer-reviewed quarterly journal and reference publisher for evidence-based herbalism. Publishers of the English translation of the German Commission E monographs.

herbalgram.org →

Herbal Medicine: Expanded Commission E Monographs

Blumenthal et al., American Botanical Council (2000) — the English translation and expansion of the German Federal Health Authority's Commission E review of 324 herbs (1978–1994). Historical foundation for Western evidence-based phytotherapy.

British Herbal Pharmacopoeia and British Herbal Compendium

British Herbal Medical Association — quality standards for 169 herbs (BHP) plus volumes of scientific information and monographs (Compendium). The British counterpart to AHP.

bhma.info →

Botanical Adulterants Prevention Program

Joint program of the American Herbal Pharmacopoeia, American Botanical Council, and the National Center for Natural Products Research at the University of Mississippi. Documents and addresses adulteration in commercial herbal products — directly relevant to "the supplement may not contain what the label says" claims.

botanicaladulterants.org →

Tier 5 — Traditional medicine literature

For compounds rooted in traditional medicine systems, we reference the relevant traditional pharmacopoeia explicitly as traditional-use evidence — distinct from RCT-grade modern research:

Ayurvedic Pharmacopoeia of India

For compounds in the Ayurvedic tradition.

WHO TCM Monographs

For compounds in Traditional Chinese Medicine.

who.int →

EMA Herbal Monographs (Traditional Use)

These explicitly distinguish “traditional use” registration from “well-established use” registration. We preserve that distinction in our analysis.

ema.europa.eu →

WHO International Standard Terminologies on Traditional Medicine

The WHO standardization framework for traditional medicine terminology, supporting consistent classification of traditional-use evidence across WHO member states.

who.int →

Pharmacopoeia of the People's Republic of China (PPRC)

The official pharmacopoeia of the PRC, including extensive monographs on Traditional Chinese Medicine materia medica with quality and identity standards.

These sources matter because dismissing them would mean ignoring documented evidence on compounds humans have used for centuries. Including them honestly means flagging them as the type of evidence they are — distinct from RCT-grade modern research, distinct again from integrative-medicine synthesis (Tier 4), preserved as their own knowledge tradition.

Tier 6 — National regulators (legal context)

National regulators close the source hierarchy because their authority is legal, not scientific. We cite them for what they are authoritative on: legal status, approved indications, formal warnings, and prescribing information for specific markets. When the regulatory position aligns with the current science, we say so. When it diverges, we name the divergence and present the science.

FDA prescribing information

For what's approved, what's contraindicated, and what's specifically warned against in US-marketed prescription drugs.

fda.gov →

EMA (European Medicines Agency)

For European market approvals, herbal monographs, and post-market safety actions.

ema.europa.eu →

DEA scheduling

For US controlled substance status, framed clearly as legal status (not as scientific assessment of risk).

dea.gov →

Other national regulators

MHRA (United Kingdom Medicines and Healthcare products Regulatory Agency), TGA (Australia Therapeutic Goods Administration), Health Canada (including the Drug Product Database and Natural Health Products Database), PMDA (Japan Pharmaceuticals and Medical Devices Agency), and Swissmedic. Cited where users' regional context calls for them.

DailyMed (NLM)

Structured FDA-derived drug labeling, maintained by the National Library of Medicine. Primary US source for current prescribing information in machine-readable form.

dailymed.nlm.nih.gov →

FDA Adverse Event Reporting System (FAERS)

FDA's pharmacovigilance database for post-market adverse event reports. Cited for known safety signals where applicable.

fda.gov →

FDA pharmacogenomic biomarkers list

The FDA's regulatory list of pharmacogenomic biomarkers in approved drug labeling. Complements PharmGKB / CPIC (Tier 3) by reflecting where pharmacogenomic information has reached US regulatory recognition.

fda.gov →

We frame these citations as what they are: regulatory positions, not scientific consensus. When the regulatory position aligns with current science, we say so. When it diverges, we explain the divergence and present the science.

Tier 0 — Preliminary (in vitro / animal)

Preliminary findings from in vitro studies or animal-only data — pre-clinical evidence not yet validated in humans. When a claim rests only on this, the analyzer flags it explicitly, so you can weigh it as the early-stage signal it is.

None — Insufficient peer-reviewed evidence

No peer-reviewed evidence base supports the claim. The analyzer says so plainly rather than manufacturing a plausible answer, and defers to your healthcare provider. T0 and None close the scale so that every tier a finding can carry is accounted for here.

03.

What the corpus actually contains

The tier hierarchy above isn’t a list of sources the analyzer looks up at runtime. It’s the editorial universe of evidence Regimens is built to reason within — the texts, databases, references, and clinical materials that informed the analyzer’s training and that anchor the curated framing for specific compounds. When the corpus expands, the framing expands; the analyzer doesn’t gain new runtime reach, it gains better-grounded priors and more curated overrides. The curated citations behind specific compounds are published below in “Cited evidence, by compound” — the actual references, with their evidence tiers and direct links.

04.

How we read the sources

Here is the honest mechanical truth about how Regimens produces its analyses, because the editorial discipline depends on you understanding it.

Regimens uses Anthropic’s Claude as its analytical engine. Claude does not look up documents at runtime. It generates its responses from statistical patterns absorbed during training — a training corpus that included peer-reviewed pharmacology literature, regulatory advisories, structured clinical references, and the other source types named in the tier hierarchy above. So when Claude produces a claim about a drug interaction, that claim is genuinely informed by those sources. But it is not extracted from any one of them.

This matters because it shapes what “source fidelity” honestly means here. If we asked Claude to attach a specific paper to each individual claim, it would generate a plausible-sounding attribution that it did not actually consult — citation theater that looks rigorous but introduces fabrication into the very layer that’s supposed to defend against it. So we don’t do that.

What we do instead is the discipline this whole page describes:

We don’t fill gaps with plausibility. When the curated source hierarchy doesn’t support a claim, the analyzer is instructed to label the evidence as insufficient — not to generate a plausible-sounding answer to fill the silence.

We don’t smooth disagreement. When peer-reviewed pharmacology and a regulator’s position diverge, when traditional use and modern evidence disagree, when two clinical studies contradict each other — the analyzer is instructed to name the divergence, not paper over it.

We use the tier signal as the load-bearing source-fidelity output. Every finding in your report carries a tier label honestly indicating the strength of evidence behind it. T1 means peer-reviewed pharmacology and clinical research supports the claim. T6 means it’s grounded only in regulatory framing, not science. NONE means the corpus doesn’t support the claim at all and we’re saying so.

We curate context overrides for the compounds where general training is known to be weak. Where the analyzer would otherwise reason from stale or contested training data, Regimens injects curator-authored framing directly into the prompt so the analysis reasons from the curated framing instead.

This is what source-fidelity actually looks like at the layer Regimens operates. The tier hierarchy above is the universe of evidence the analyzer is built to reason within. The per-finding tier label tells you how strongly that universe supports each specific claim. That’s the honest commitment, and it’s what we’re building everything else on.

05.

What we don’t do

We don't pretend our analysis is medical advice.

It isn't. Always consult your doctor and healthcare team before making changes to your regimen.

We don't claim diagnostic capability.

Regimens identifies documented interactions and patterns; it doesn't diagnose conditions or replace clinical evaluation.

We don't have access to your medical records.

Our analysis is based on the regimen you log, the personal health profile you share with us, and our source corpus. We can't account for medical history we don't know about.

We don't run live searches.

Regimens AI uses a frozen knowledge corpus, plus structured prompts that prioritize the source hierarchy above. New research published after the model's training date won't be reflected — and we say that directly when it might matter.

We're not HIPAA-covered.

Regimens is a working tool for personal pharmacology, explicitly not a clinical service or HIPAA-covered application. Our privacy policy explains how we handle the data you share with us.

06.

How we work against AI’s failure modes

Our analysis is generated by Regimens AI, configured with the source hierarchy described above. Like all AI systems, it can occasionally generate plausible-sounding but inaccurate information.

Generative AI fabricates plausible-sounding sources when asked to attach specific citations to individual claims. Regimens doesn’t pretend otherwise. The defenses described on this page are designed to honor what the underlying mechanism actually does — and to refuse the kinds of attribution it can’t honestly produce. The four disciplines this page describes — a curated source corpus, a per-finding evidence-tier signal (T1, T1.5, T2, T3, T4, T5, T6, T0, NONE), curated context overrides for compounds where training data is thin or stale, and explicit gap-flagging — are what source fidelity actually looks like at this layer.

We don’t claim our analysis is perfect. We claim it’s better-grounded and more honestly framed than any wellness AI tool we know of, and we welcome corrections from clinicians, researchers, and informed users.

07.

Questions or corrections?

If you believe a claim is misframed against the evidence, or a source in our corpus is wrong, we want to know. Email support@regimens.app with specifics. We’ll investigate and update.

08.

Cited evidence, by compound

The sources below back the compound information in Regimens. Each is a curator-verified reference at a stated evidence tier; where a DOI or PubMed ID is available it links directly to the source.

7-OH

  • T0 · Preliminary (in vitro / animal)Todd 2020, Sci Rep 10:19158 (doi 10.1038/s41598-020-76119-w) — 7-OH at the human µ-opioid receptor, in vitro
  • T6 · FDA AdvisoryFDA 2025, "7-Hydroxymitragynine (7-OH): An Assessment of the Scientific Data and Toxicological Concerns Around an Emerging Opioid Threat" (fda.gov; NPDS data through Apr 2025)
  • T6 · FDA AdvisoryFDA 2025, "7-Hydroxymitragynine (7-OH): An Assessment of the Scientific Data and Toxicological Concerns Around an Emerging Opioid Threat" (fda.gov; NPDS data through Apr 2025)
  • T6 · FDA AdvisoryFDA warning letters to 7 firms marketing 7-OH products, dated June 25, 2025 (announced July 15, 2025; representative: Hydroxie LLC, MARCS-CMS 709661) — tablets, gummies, drink mixes, shots
  • T6 · FDA AdvisoryFDA recommendation to HHS/DEA for CSA scheduling of 7-OH, July 29, 2025 (HHS release) + FDA/DOJ seizure action, Dec 2, 2025 (~73,000 units, ~$1M, three Missouri firms)
  • T6 · DEA ScheduleDEA notices of intent: 91 FR 40917 (Jul 6, 2026, Docket DEA-1570) and revised notices Oct 14, 2026 (FR Docs 2026-20943 / 2026-20942) — temporary Schedule I placement of 7-OH above threshold
  • T6 · DEA ScheduleDEA temporary scheduling ORDER, 91 FR 54948 (Aug 26, 2026, Docket DEA-1644) — mitragynine pseudoindoxyl (MP), MGM-15, MGM-16 placed in Schedule I
  • T6 · FDA AdvisoryFDA, "FDA and Kratom" (fda.gov, current 12/02/2025) — the 7-OH passage

Apixaban

  • T3 · PubMedSt John's Wort as a strong CYP3A4/P-gp inducer — class evidence (Huppertz 2018 rivaroxaban AUC −26%; Jiang 2004 warfarin effect −21%); apixaban-specific magnitude label-qualitative (Eliquis §7.2 names SJW to avoid)
  • T6 · FDA PrescribingFDA apixaban (Eliquis) prescribing label §12.3 / §2 (food) + §7.1–7.2 (CYP3A4/P-gp)

Atorvastatin

  • T1 · PubMedBailey 2013, CMAJ 185:309 (PMID 23184849) — grapefruit mechanism + dose-dependence
  • T6 · FDA PrescribingFDA atorvastatin (Lipitor) prescribing label §5.1 / §7.1 / §12.3 / Table 2 / Table 5

BPC-157

  • T0 · Preliminary (in vitro / animal)He 2022, Front Pharmacol 13:1026182 (doi 10.3389/fphar.2022.1026182, PMID 36588717) — the only pharmacokinetic study: rats and beagle dogs, IV and IM, radiolabeled
  • T0 · Preliminary (in vitro / animal)Staresinic 2003, J Orthop Res 21:976 (doi 10.1016/S0736-0266(03)00110-4, PMID 14554208) — rat Achilles tendon transection, 10 µg–10 pg/kg i.p. daily; companion: Staresinic 2006 (PMID 16609979), rat quadriceps transection
  • T0 · Preliminary (in vitro / animal)Hsieh 2017, J Mol Med 95:323 (doi 10.1007/s00109-016-1488-y, PMID 27847966) — rat hind-limb ischemia + human endothelial cells, VEGFR2 mechanism
  • T0 · Preliminary (in vitro / animal)Chang 2014, Molecules 19:19066 (doi 10.3390/molecules191119066, PMID 25415472) — in vitro, rat tendon fibroblasts
  • T1 · PubMedVasireddi 2025, HSS J 21:485 (doi 10.1177/15563316251355551, PMID 40756949) — PRISMA systematic review, orthopaedic sports medicine use of BPC-157: 544 records screened, 36 included
  • T1.5 · Peptide Clinical PracticeMcGuire 2025, Curr Rev Musculoskelet Med 18:611 (doi 10.1007/s12178-025-09990-7, PMID 40789979) — clinical-practice narrative review, musculoskeletal use
  • T3 · PubMedLee 2021, Altern Ther Health Med 27(4):8 (PMID 34324435) — retrospective knee-pain case series, single private clinic, n=16 followed, 4 mg intra-articular BPC-157
  • T3 · PubMedLee 2024, Altern Ther Health Med 30(10):12 (PMID 39325560) — interstitial cystitis pilot, n=12 women, single 10 mg cystoscopic injection
  • T3 · PubMedLee 2025, Altern Ther Health Med 31(5):20 (PMID 40131143) — IV tolerability pilot, n=2, 10 then 20 mg IV over 1 h
  • T6 · FDA AdvisoryFDA 503A bulk drug substances action, Sept 29 2023 (Category 2 — significant safety risk) + subsequent nomination withdrawal (FDA "may present significant safety risks" page) + Warning Letter MARCS-CMS 655280 (Warrior Labz, June 12 2023)

Ciprofloxacin

  • T1 · PubMedPitman 2019, Antibiotics 8:108 (doi 10.3390/antibiotics8030108) — review of oral fluoroquinolone × multivalent cation interactions
  • T3 · PubMedNeuvonen 1991, Clin Pharmacol Ther 50:498 (doi 10.1038/clpt.1991.174) — crossover, n=7, ciprofloxacin 500 mg ± dairy
  • T3 · PubMedPolk 1989, Antimicrob Agents Chemother 33:1841 (doi 10.1128/AAC.33.11.1841) — n=12, ciprofloxacin 500 mg ± ferrous sulfate / multivitamin+zinc
  • T6 · FDA PrescribingFDA ciprofloxacin tablets prescribing label (Hikma SPL, §17 Patient Counseling / §12.3) — current
  • T6 · FDA PrescribingFDA ciprofloxacin label §12.3/§17 — caffeine (CYP1A2)

Collagen

  • T1 · PubMedPu 2023, Nutrients 15:2080 (PMID 37432180) — systematic review + meta-analysis, 26 RCTs, n=1721, hydrolyzed collagen for skin
  • T1 · PubMedMyung & Park 2025, Am J Med 138:1264 (doi 10.1016/j.amjmed.2025.04.034, PMID 40324552) — meta-analysis, 23 RCTs, n=1474, with funding-source and quality subgroups; non-industry authors (Korea NCC/Monash)
  • T1 · PubMedGarcía-Coronado 2019, Int Orthop 43:531 (doi 10.1007/s00264-018-4211-5, PMID 30368550) — meta-analysis of placebo-controlled RCTs, oral collagen for osteoarthritis
  • T1 · PubMedLugo 2016, Nutr J 15:14 (doi 10.1186/s12937-016-0130-8, PMID 26822714) — multicenter RCT, n=191 knee OA, UC-II 40 mg/d vs glucosamine 1500 mg + chondroitin 1200 mg vs placebo, 180 d; SPONSOR-RUN (InterHealth Nutraceuticals — sponsor's employees are first two authors)
  • T1 · PubMedOikawa 2020, Am J Clin Nutr 111:708 (doi 10.1093/ajcn/nqz332, PMID 31919527) — RCT, n=22 older women, 30 g whey vs 30 g collagen 2×/d, tracer-measured muscle protein synthesis; corroborated by Jacinto 2022 (PMID 35042187), 10-wk training RCT
  • T3 · PubMedProksch 2014, Skin Pharmacol Physiol 27:47 (doi 10.1159/000351376, PMID 23949208) — RCT, n=69 women 35–55, VERISOL 2.5 g or 5.0 g vs maltodextrin, 8 wk; product provided by GELITA AG, co-authors from the GELITA-linked Collagen Research Institute
  • T3 · PubMedClark 2008, Curr Med Res Opin 24:1485 (PMID 18416885) — RCT, 147 athletes with activity-related knee pain, 10 g collagen hydrolysate × 24 wk (GELITA AG employee co-author); companion Zdzieblik 2017, Appl Physiol Nutr Metab 42:588 (PMID 28177710) — n=139 athletes, 5 g/d × 12 wk, CRI co-author
  • T3 · PubMedKönig 2018, Nutrients 10:97 (PMID 29337906) — RCT, n=131 postmenopausal women with reduced BMD, 5 g specific collagen peptides (FORTIBONE, GELITA AG) vs maltodextrin, 12 months
  • T3 · PubMedShaw & Baar 2017, Am J Clin Nutr 105:136 (doi 10.3945/ajcn.116.138594, PMID 27852613) — double-blind crossover, n=8, vitamin C-enriched gelatin 5 or 15 g taken 1 h before 6 min of rope-skipping; NIH/university funded (not industry)
  • T3 · PubMedIwai 2005, J Agric Food Chem 53:6531 (PMID 16076145) — human PK, 9.4–23 g gelatin hydrolysates: peptide-form hydroxyproline in plasma; companion Shigemura 2011 (PMID 25212331, Hyp-Gly); rat 14C distribution: Watanabe-Kamiyama 2010 (PMID 19957932)

Creatine

  • T1 · PubMedLanhers 2017, Sports Med (doi 10.1007/s40279-016-0571-4, PMID 27328852) — meta-analysis, 53 double-blind placebo-controlled RCTs, n=1138, upper-limb strength
  • T1 · PubMedLanhers 2015, Sports Med (doi 10.1007/s40279-015-0337-4, PMID 25946994) — meta-analysis, 60 RCTs, n=1297, lower-limb strength
  • T1 · PubMedChilibeck 2017, Open Access J Sports Med 8:213 (doi 10.2147/OAJSM.S123529, PMID 29138605) — meta-analysis, 22 RCTs, n=721 older adults (mean ages 57–70) during resistance training
  • T1 · PubMedAvgerinos 2018, Exp Gerontol 108:166 (doi 10.1016/j.exger.2018.04.013, PMID 29704637) — systematic review of RCTs on cognition, 6 trials, n=281 healthy individuals
  • T1 · PubMedde Souza e Silva 2019, J Ren Nutr 29:480 (doi 10.1053/j.jrn.2019.05.004, PMID 31375416) — systematic review + meta-analysis, renal function (15 studies qualitative, 6 quantitative)
  • T1.5 · Peptide Clinical PracticeKreider 2017, J Int Soc Sports Nutr 14:18 (doi 10.1186/s12970-017-0173-z) — ISSN Position Stand: safety and efficacy of creatine supplementation
  • T1.5 · PubMedCommission Regulation (EU) 432/2012 annex (basis EFSA Journal 2011;9(7):2303) + Commission Implementing Regulation (EU) 2017/672 (basis EFSA Journal 2016;14(2):4400) — the two authorized EU health claims for creatine
  • T2 · NIH ODSNIH ODS, Dietary Supplements for Exercise and Athletic Performance — Health Professional Fact Sheet (ods.od.nih.gov/factsheets/ExerciseAndAthleticPerformance-HealthProfessional). No standalone creatine fact sheet exists — creatine is covered here
  • T3 · PubMedHultman 1996, J Appl Physiol 81:232 — muscle creatine loading PK, n=31 healthy men, biopsy-verified, 4 arms
  • T3 · PubMedvan der Merwe 2009, Clin J Sport Med 19:399 (doi 10.1097/JSM.0b013e3181b8b52f, PMID 19741313) — crossover, n=20 college rugby players, 25 g/d × 7 d then 5 g/d × 14 d

Doxycycline

  • T3 · PubMedNeuvonen 1970, Br Med J 4:532 — iron interference with tetracycline absorption in man
  • T6 · FDA AdvisoryFDA doxycycline (DORYX) prescribing label §7.3 / §17 / §12.3 / §2.1
  • T6 · FDA PrescribingFDA doxycycline label §7.3 — antacids/cations class statement

Furosemide

  • T3 · PubMedRieck 1999, J Lab Clin Med 134:238 (doi 10.1016/s0022-2143(99)90203-2) — furosemide increases urinary thiamine; + Seligmann 1991, Am J Med 91:151 (CHF thiamine deficiency)
  • T6 · PubMedFDA furosemide (Lasix) prescribing label — Precautions + Laboratory Tests + Drug Interactions

Hydrochlorothiazide

  • T3 · PubMedStørmer 1993, Food Chem Toxicol 31:303 (PMID 8386690) — glycyrrhizin/licorice pseudohyperaldosteronism (additive hypokalemia)
  • T6 · FDA PrescribingFDA hydrochlorothiazide prescribing label — Precautions/General + Adverse Reactions

Isocarboxazid

  • T3 · PubMedVan den Eynde/Gillman 2022 modernized MAOI diet vs the Marplan label's conservative list
  • T6 · FDA PrescribingFDA isocarboxazid (Marplan) prescribing label (rev. Dec 2025) — CONTRAINDICATIONS (tyramine foods)

KavaPiper methysticum

  • T0 · Preliminary (in vitro / animal)Chua 2016, PLoS One 11:e0157700 (PMID 27332705) — kavain at recombinant GABA-A receptors
  • T0 · Preliminary (in vitro / animal)Zhou 2010, FASEB J 24:4722 (PMID 20696856) — flavokawain B hepatotoxicity (in vitro + mouse)
  • T2 · Codex AlimentariusCXS 336R-2020 — Codex regional standard for kava products for use as a beverage when mixed with water (adopted CAC43, Sept 25 2020)
  • T3 · PubMedMathews 2002, Drug Metab Dispos 30:1153 — kava extract/kavalactones vs human CYP450 in vitro; in vivo companion: Gurley 2005, Clin Pharmacol Ther 77:415 (PMID 15900287)
  • T3 · PubMedAlmeida & Grimsley 1996, Ann Intern Med 125:940 (PMID 8967683) — coma from kava + alprazolam
  • T3 · PubMedSarris 2013, Traffic Inj Prev 14:13 (PMID 23259514) — driving simulator, kava 180 mg kavalactones vs oxazepam vs placebo; Aporosa 2022, J Ethnopharmacol 291:115080 (PMID 35151837) — traditional sessions (~6 h, ~3.6 L)
  • T3 · PubMedNorton & Ruze 1994, J Am Acad Dermatol 31:89 (PMID 8021378) — kava dermopathy; Clough 2003, Intern Med J 33:336 (PMID 12895162) — heavy-use biochemistry, Arnhem Land, n=101
  • T4 · NCCIHNCCIH, "Kava — Usefulness and Safety" (nccih.nih.gov/health/kava, updated April 2025)
  • T6 · FDA AdvisoryFDA CFSAN Scientific Memorandum: Kava, Aug 11 2020 (fda.gov/media/169556/download) — the agency's position on BEVERAGE/conventional-food use; context: the 2002 supplement advisory (archived, unrevised)

Kava ExtractPiper methysticum

  • T0 · Preliminary (in vitro / animal)Chua 2016, PLoS One 11:e0157700 (PMID 27332705) — kavain at GABA-A receptors
  • T0 · Preliminary (in vitro / animal)Zhou 2010, FASEB J 24:4722 (PMID 20696856) — flavokawain B hepatotoxicity (in vitro + mouse)
  • T1 · Cochrane ReviewPittler & Ernst 2003, Cochrane CD003383 (PMID 12535473) — kava extract for anxiety: 11 RCTs, n=645
  • T1 · PubMedSarris 2013, J Clin Psychopharmacol 33:643 (PMID 23635869) — DB-RCT, n=75, aqueous dried-root extract 120/240 mg kavalactones/d × 6 wk, GAD
  • T1 · PubMedSarris 2020, Aust N Z J Psychiatry 54:288 (PMID 31813230) — Phase III, n=171 GAD, aqueous extract 240 mg kavalactones/d × 16 wk — largest and longest kava trial
  • T1 · PubMedOoi 2018, J Altern Complement Med 24:770 (PMID 29641222) — GAD meta; Smith & Leiras 2018, Complement Ther Clin Pract 33:107 (PMID 30396607) — responder-rate meta, 11 trials
  • T1.5 · PubMedBandelow 2008, WFSBP anxiety guidelines (first revision), World J Biol Psychiatry 9:248
  • T3 · PubMedAlmeida & Grimsley 1996, Ann Intern Med 125:940 (PMID 8967683) — coma from kava + alprazolam
  • T3 · PubMedTeschke 2008, Eur J Gastroenterol Hepatol 20:1182 (PMID 18989142) — CIOMS/RUCAM assessment of the 26 German/Swiss regulatory cases
  • T3 · PubMedMathews 2002, Drug Metab Dispos 30:1153 — kava extract/kavalactones vs human CYP450 in vitro; in vivo: Gurley 2005 (PMID 15900287), n=12, 28 d supplement dosing
  • T4 · NCCIHNCCIH, "Kava — Usefulness and Safety" (April 2025)
  • T6 · FDA AdvisoryFDA/CFSAN consumer advisory, March 25 2002: "Kava-Containing Dietary Supplements May Be Associated With Severe Liver Injury" (archived; never revised or withdrawn) + CFSAN Scientific Memorandum, Aug 11 2020

KratomMitragyna speciosa

  • T0 · Preliminary (in vitro / animal)Kruegel 2019, ACS Cent Sci 5:992 (doi 10.1021/acscentsci.9b00141) — 7-OH as active metabolite of mitragynine (mouse in vivo; mouse + human liver preparations)
  • T0 · Preliminary (in vitro / animal)Todd 2020, Sci Rep 10:19158 (doi 10.1038/s41598-020-76119-w) — receptor pharmacology, human µ-opioid receptor in vitro
  • T1 · PubMedVicknasingam 2020, Yale J Biol Med 93:229 (PMID 32607084) — randomized, placebo-controlled, double-blind cold-pressor study, n=26 male daily kratom users (mean 6.1 y use), kratom decoction vs placebo
  • T3 · PubMedKamble 2020, Toxicol Lett 319:148 (doi 10.1016/j.toxlet.2019.11.005) — CYP inhibition screening, human liver microsomes; NIDA-funded (UG3 DA048353, R01 DA047855), no industry conflicts
  • T3 · PubMedTanna 2023, Drug Metab Dispos 51:923 (doi 10.1124/dmd.122.001005) — NCCIH/NIDA Natural Product Drug Interaction center; time-dependent CYP3A inhibition + transporters
  • T3 · PubMedOlsen 2019, MMWR 68:326 (doi 10.15585/mmwr.mm6814a2) — CDC SUDORS, unintentional overdose deaths with kratom detected, 27 states, Jul 2016–Dec 2017
  • T3 · PubMedNavarro 2019, DILIN Prospective Study case series (AASLD abstract 0212, Hepatology) — kratom hepatotoxicity among 404 herbal/dietary-supplement liver-injury cases, 2004–2018
  • T4 · PubMedTanna 2023, Clin Pharmacol Ther (PMID 36924284) — human drug-interaction study, single 2 g kratom tea dose, healthy adults, midazolam (CYP3A) + dextromethorphan (CYP2D6) probes
  • T6 · FDA AdvisoryFDA, "FDA and Kratom" (fda.gov/news-events/public-health-focus/fda-and-kratom; content current 12/02/2025)
  • T6 · FDA AdvisoryFDA Import Alert 54-15 (accessdata.fda.gov/cms_ia/importalert_1137.html) — detention without physical examination of kratom-containing dietary products; first issued Feb 2014, actively updated (Red List addition 08/17/2026)
  • T6 · DEA ScheduleDEA, 81 FR 59929 (Aug 31, 2016, Docket DEA-442) notice of intent to place mitragynine + 7-OH in Schedule I — WITHDRAWN at 81 FR 70652 (Oct 13, 2016, Docket DEA-442W)

Kratom ExtractMitragyna speciosa

  • T0 · Preliminary (in vitro / animal)Kruegel 2019, ACS Cent Sci 5:992 (doi 10.1021/acscentsci.9b00141) — 7-OH as active metabolite of mitragynine (mouse in vivo; mouse + human liver preparations)
  • T0 · PubMedTodd 2020, Sci Rep 10:19158 (doi 10.1038/s41598-020-76119-w) — receptor pharmacology, human µ-opioid receptor in vitro
  • T1 · PubMedVicknasingam 2020, Yale J Biol Med 93:229 (PMID 32607084) — randomized, placebo-controlled, double-blind cold-pressor study, n=26 male daily kratom users (mean 6.1 y use), kratom decoction vs placebo
  • T3 · PubMedKamble 2020, Toxicol Lett 319:148 (doi 10.1016/j.toxlet.2019.11.005) — CYP inhibition screening, human liver microsomes; NIDA-funded (UG3 DA048353, R01 DA047855), no industry conflicts
  • T3 · PubMedTanna 2023, Drug Metab Dispos 51:923 (doi 10.1124/dmd.122.001005) — NCCIH/NIDA Natural Product Drug Interaction center; time-dependent CYP3A inhibition + transporters
  • T3 · PubMedTanna 2023, Clin Pharmacol Ther (PMID 36924284) — human drug-interaction study, single 2 g kratom tea dose, healthy adults, midazolam (CYP3A) + dextromethorphan (CYP2D6) probes
  • T3 · PubMedOlsen 2019, MMWR 68:326 (doi 10.15585/mmwr.mm6814a2) — CDC SUDORS, unintentional overdose deaths with kratom detected, 27 states, Jul 2016–Dec 2017
  • T6 · FDA AdvisoryFDA, "FDA and Kratom" (fda.gov, current 12/02/2025) + Import Alert 54-15 (updated through 08/17/2026 — expressly covers "resins, extracts, bulk liquids")
  • T6 · FDA AdvisoryFDA 2025, "7-Hydroxymitragynine (7-OH): An Assessment of the Scientific Data and Toxicological Concerns Around an Emerging Opioid Threat" (fda.gov; data through mid-2025) — product-chemistry findings for concentrated extracts
  • T6 · DEA ScheduleDEA 2016 notice + withdrawal (81 FR 59929 / 81 FR 70652) — as Compound A anchor 11; plus the Oct 14, 2026 revised 7-OH threshold design (FR Doc 2026-20943): control attaches above 1 mg/g 7-OH OR mitragynine:7-OH ratio <100

Levofloxacin

  • T1 · PubMedPitman 2019, Antibiotics 8:108 (doi 10.3390/antibiotics8030108), Table 1 (attributing Shiba 1992) — levofloxacin × cations
  • T3 · PubMedFish & Chow 1997, Clin Pharmacokinet 32:101 (PMID 9068926) — levofloxacin clinical pharmacokinetics
  • T6 · FDA PrescribingFDA levofloxacin tablets prescribing label (§2.4 / §7.1) — current

Levothyroxine

Linezolid

  • T6 · FDA PrescribingFDA linezolid (Zyvox) prescribing label — Drug Interactions + §17 counseling
  • T6 · FDA AdvisoryFDA linezolid label (serotonin syndrome) + FDA Drug Safety Communication on methylene blue (2011-07-26, a second hidden MAOI)

Lisinopril

  • T1 · PubMedLapi 2013, BMJ 346:e8525 (doi 10.1136/bmj.e8525, PMID 23299844) — the NSAID "triple whammy" AKI, nested case-control, 487,372 patients
  • T6 · FDA PrescribingFDA lisinopril prescribing label §5.5 (Hyperkalemia) / §7.1 / §12.1 / §17
  • T6 · FDA PrescribingFDA lisinopril label §6.1 (cough) + §7.5 (lithium)

Losartan

  • T6 · FDA PrescribingFDA losartan prescribing label §5.4 (Hyperkalemia) / §7.1 / §17
  • T6 · FDA PrescribingFDA losartan label §6.1 (cough rechallenge) + §7.2 (lithium)

Lovastatin

  • T1 · PubMedBailey 2013, CMAJ 185:309 (PMID 23184849) — grapefruit mechanism (shared with simvastatin anchor A2)
  • T6 · FDA PrescribingFDA lovastatin (Mevacor) prescribing label — Clinical Pharmacology + Table I + Table VII + Precautions

Magnesium Glycinate

  • T1 · PubMedZhang 2016, Hypertension 68:324 (doi 10.1161/HYPERTENSIONAHA.116.07664, PMID 27402922) — meta-analysis, 34 double-blind placebo-controlled RCTs, n=2028, median 368 mg/d × 3 mo
  • T1 · Cochrane ReviewGarrison 2020, Cochrane CD009402 (doi 10.1002/14651858.CD009402.pub3, PMID 32956536) — 11 RCTs, n=735, magnesium for skeletal muscle cramps
  • T1 · PubMedMah & Pitre 2021, BMC Complement Med Ther 21:125 (doi 10.1186/s12906-021-03297-z, PMID 33865376) — systematic review + meta-analysis, magnesium for insomnia: 3 RCTs, n=151 older adults
  • T1.5 · PubMedHolland 2012, AAN/AHS evidence-based guideline update, Neurology 78:1346 (doi 10.1212/WNL.0b013e3182535d0c, PMID 22529203) — episodic migraine prevention
  • T2 · NIH ODSNIH ODS Magnesium Fact Sheet for Health Professionals (ods.od.nih.gov/factsheets/Magnesium-HealthProfessional)
  • T3 · PubMedTarleton 2017, PLoS ONE 12:e0180067 (PMID 28654669) — open-label randomized crossover, n=126, 248 mg/d elemental (as chloride) × 6 wk, mild-moderate depression; companion: Boyle 2017 SR, Nutrients 9:429 (PMID 28445426), anxiety
  • T3 · PubMedAbbasi 2012, J Res Med Sci 17:1161 (PMID 23853635) — double-blind RCT, n=46 elderly primary insomnia, 500 mg/d × 8 wk
  • T3 · PubMedWalker 2003, Magnes Res 16:183 (PMID 14596323) — RCT n=46, citrate vs amino-acid chelate vs oxide, 300 mg/d × 60 d; companions: Firoz & Graber 2001 (PMID 11794633, oxide fractional absorption 4%), Lindberg 1990 (PMID 2407766, citrate ≫ oxide solubility/urinary response)
  • T3 · PubMedSchuette 1994, JPEN 18:430 (doi 10.1177/0148607194018005430, PMID 7815675) — double-blind crossover, n=12 ileal-resection patients, 26Mg-labeled bisglycinate vs oxide
  • T3 · PubMedSupakatisant & Phupong 2015, Matern Child Nutr 11:139 (doi 10.1111/j.1740-8709.2012.00440.x, PMID 22909270) — double-blind RCT, n=86 pregnant women with leg cramps, magnesium BISGLYCINATE 300 mg/d × 4 wk
  • T3 · PubMedPeikert 1996, Cephalalgia 16:257 (PMID 8792038) — RCT, n=81 migraineurs, 600 mg/d elemental (trimagnesium dicitrate) × 12 wk
  • T6 · FDA AdvisoryFDA Drug Safety Communication, March 2, 2011 — low serum magnesium associated with long-term proton-pump-inhibitor use (fda.gov)

Metformin

  • T1 · PubMedAroda 2016, J Clin Endocrinol Metab 101:1754 (doi 10.1210/jc.2015-3754, PMID 26900641) — DPP/DPPOS, metformin and B12
  • T3 · PubMedBauman 2000, Diabetes Care 23:1227 (PMID 10977010) — oral calcium reverses metformin-induced B12 malabsorption
  • T6 · FDA PrescribingFDA metformin prescribing label §5.2 (Vitamin B12 Deficiency)

Minocycline

  • T3 · PubMedNeuvonen 1970, Br Med J 4:532 — iron × tetracyclines (class); + tetracycline HCl FDA label (names zinc + sodium bicarbonate)
  • T6 · FDA PrescribingFDA minocycline HCl prescribing label §7.3

NMN

  • T0 · Preliminary (in vitro / animal)Mills 2016, Cell Metab 24:795 (doi 10.1016/j.cmet.2016.09.013) — 12-month mouse study
  • T1 · PubMedYoshino 2021, Science 372:1224 (doi 10.1126/science.abe9985) — RCT, 25 prediabetic postmenopausal women, 250 mg/d × 10 wk
  • T1 · PubMedYi 2023, GeroScience (doi 10.1007/s11357-022-00705-1) — RCT, 80 adults, 300/600/900 mg/d × 60 d; SPONSOR-RUN (manufacturer)
  • T1 · PubMedFukamizu 2022, Sci Rep 12:14442 (doi 10.1038/s41598-022-18272-y) — RCT, 1250 mg/d × 4 wk; Mitsubishi-funded
  • T1 · PubMedSong 2023, Adv Nutr 14:1416 (doi 10.1016/j.advnut.2023.08.008) — systematic review, 10 human trials
  • T2 · NIH ODSNIH ODS Niacin fact sheet (ods.od.nih.gov/factsheets/Niacin-HealthProfessional)
  • T3 · PubMedOkabe 2022, Front Nutr (doi 10.3389/fnut.2022.868640) — RCT, 250 mg/d × 12 wk; Mitsubishi-funded
  • T3 · PubMedIgarashi 2022, npj Aging (doi 10.1038/s41514-022-00084-z) — RCT, men ≥65, 250 mg/d × 12 wk; n=10/arm at endpoint
  • T3 · PubMedKim 2022, Nutrients 14:755 (doi 10.3390/nu14040755) — RCT, 108 adults ≥65, AM vs PM 250 mg × 12 wk
  • T6 · FDA PrescribingFDA response to docket FDA-2023-P-1867, Sept 29 2025 + NDIN reinstatement letters Dec 2 2025

Omega-3

Omeprazole

  • T1 · PubMedLam 2013, JAMA 310:2435 (doi 10.1001/jama.2013.280490, PMID 24327038) — PPI/H2RA and B12 deficiency, case-control, 25,956 cases vs 184,199 controls
  • T1 · PubMedLam 2017, Gastroenterology 152:821 (PMID 27890768) — PPI and iron deficiency, case-control, 77,046 cases vs 389,314 controls
  • T6 · FDA AdvisoryFDA omeprazole label §5.8 (Hypomagnesemia), codifying the FDA Drug Safety Communication of March 2, 2011
  • T6 · FDA AdvisoryFDA omeprazole label §5.4 (Bone Fracture)

Phenelzine

  • T3 · PubMedVan den Eynde, Gillman & Blackwell 2022, Psychopharmacol Bull 52(2):73 — "The Prescriber's Guide to the MAOI Diet"; + WRHA low-tyramine guideline (Gardner 1996 basis)
  • T6 · FDA PrescribingFDA phenelzine (Nardil) prescribing label — CONTRAINDICATIONS + WARNINGS "Foods and Beverages To Avoid"
  • T6 · FDA PrescribingFDA Nardil label — serotonin-syndrome / contraindicated serotonergic combinations + MAOI washout

PomegranatePunica granatum

  • T0 · Preliminary (in vitro / animal)Hidaka 2005, Drug Metab Dispos (doi 10.1124/dmd.104.002824) — human liver microsomes + rats, carbamazepine CYP3A; companion: Nagata 2007, Drug Metab Dispos 35:302 (PMID 17132763), CYP2C9/tolbutamide in rats
  • T1 · PubMedHanley 2012, Clin Pharmacol Ther 92:651 (doi 10.1038/clpt.2012.170, PMID 23047652) — 4-period crossover, n=12 healthy adults, flurbiprofen 100 mg with pomegranate juice (250 mL) vs pomegranate extract (1 g) vs fluconazole vs control; CYP2C9 probe
  • T1 · PubMedFarkas 2007, J Clin Pharmacol 47:286 (doi 10.1177/0091270006298359, PMID 17322140) — healthy-volunteer PK study, oral + IV midazolam with pomegranate juice vs grapefruit juice; CYP3A probe
  • T1 · PubMedMisaka 2011, Clin Ther 33:246 (doi 10.1016/j.clinthera.2011.02.012, PMID 21497708) — open-label randomized 2-period crossover, healthy Japanese volunteers, 2 weeks of pomegranate juice then single-dose midazolam; CYP3A probe
  • T1 · PubMedAtkin, Sahebkar et al. 2023, Phytother Res 37:4429 (doi 10.1002/ptr.7952, PMID 37461211) — systematic review + meta-analysis, 14 trials, n=573, pomegranate juice and blood pressure
  • T3 · PubMedCase reports: Komperda 2009, Pharmacotherapy 29:1002 (PMID 19637955) + Jarvis 2010, Emerg Med J 27:74 (PMID 20029019), pomegranate juice × warfarin (raised INR); Sorokin 2006, Am J Cardiol (PMID 16923466), pomegranate juice × rosuvastatin + ezetimibe rhabdomyolysis
  • T4 · NCCIHNCCIH, "Pomegranate: Usefulness and Safety" (nccih.nih.gov/health/pomegranate, updated April 2025)

Potassium

  • T2 · NIH ODSNIH ODS Potassium Fact Sheet for Health Professionals (ods.od.nih.gov/factsheets/Potassium-HealthProfessional)
  • T2 · NIH ODSNIH ODS Potassium Fact Sheet — Interactions with Medications + impaired-excretion caution

Pravastatin

  • T6 · FDA PrescribingFDA pravastatin (Pravachol) prescribing label §12.3 / Table 4

Red Yeast RiceMonascus purpureus

  • T1 · PubMedGordon 2010, Arch Intern Med 170:1722 (doi 10.1001/archinternmed.2010.382, PMID 20975018) — monacolin variability + citrinin in commercial RYR
  • T1 · PubMedLiu 2006, Chin Med 1:4 (doi 10.1186/1749-8546-1-4) — RYR for lipids, meta-analysis of 93 RCTs, n=9,625
  • T3 · PubMedNIH LiverTox (NBK548168) — Red Yeast Rice; + EFSA ANS Panel 2018, EFSA Journal 16(8):5368 (monacolin K = lovastatin)
  • T6 · FDA AdvisoryFDA position (via NCCIH): red yeast rice with meaningful monacolin K = unapproved new drug; + FDA lovastatin label (the inherited grapefruit/CYP3A4 interaction)

ResveratrolPolygonum cuspidatum

  • T0 · PubMedPacholec 2010, J Biol Chem 285:8340 (PMID 20061378, Pfizer) — biochemistry; counter-argued by Hubbard 2013, Science 339:1216 (Sinclair/Sirtris-aligned)
  • T1 · PubMedLiu 2014, Am J Clin Nutr (doi 10.3945/ajcn.113.082024) — meta-analysis, 11 RCTs, 388 participants
  • T1 · PubMedZhu 2017, Nutr Metab 14:60 (doi 10.1186/s12986-017-0217-z) — meta-analysis, 9 RCTs, 283 T2DM patients
  • T1 · PubMedAkbari 2020, Lipids Health Dis 19:25 (doi 10.1186/s12944-020-1198-x) — meta-analysis, 31 RCTs, 1722 participants
  • T1 · PubMedAkbari 2020, Lipids Health Dis 19:25 (doi 10.1186/s12944-020-1198-x) — meta-analysis, 31 RCTs, 1722 participants
  • T1 · PubMedSemba 2014, JAMA Intern Med 174:1077 (doi 10.1001/jamainternmed.2014.1582) — prospective cohort, 783 adults ≥65, 9–11 yr, urinary resveratrol metabolites
  • T1 · PubMedGliemann 2013, J Physiol 591:5047 (doi 10.1113/jphysiol.2013.258061) — RCT, older men, 250 mg/d during 8 wk exercise training
  • T1 · PubMedYoshino 2012, Cell Metab 16:658 (doi 10.1016/j.cmet.2012.09.015) — RCT, 75 mg/d × 12 wk, nonobese women with normal glucose tolerance
  • T3 · PubMedChow 2010, Cancer Prev Res 3:1168 (PMID 20716633) — human CYP phenotyping, n=40, 1 g/d × 4 wk, probe-drug cocktail
  • T3 · PubMedWalle 2004, Drug Metab Dispos 32:1377 (doi 10.1124/dmd.104.000885) — 14C PK, 25 mg oral, 6 volunteers; corroborated by Boocock 2007 (PMID 17548692, up to 5 g)
  • T3 · PubMedla Porte 2010, Clin Pharmacokinet 49:449 (doi 10.2165/11531820-000000000-00000) — food-effect PK, 2000 mg BID

Rosuvastatin

  • T6 · FDA PrescribingFDA rosuvastatin (Crestor) prescribing label §12.3

Selegiline

  • T3 · PubMedSelegiline MAO-B selectivity — oral low-dose (Parkinson's, ≤10 mg) MAO-B-selective; selectivity lost at higher/antidepressant doses
  • T6 · FDA PrescribingFDA selegiline transdermal (Emsam) prescribing label §2.1 / §2.3 / §7.2 / §12.2

Simvastatin

  • T1 · PubMedBailey 2013, CMAJ 185:309 (doi 10.1503/cmaj.120951, PMID 23184849) — grapefruit–medication interactions mechanism review
  • T1 · PubMedQu 2018, Eur J Med Res 23:57 (doi 10.1186/s40001-018-0353-6) — statins and circulating CoQ10, meta-analysis of RCTs
  • T6 · FDA PrescribingFDA simvastatin (Zocor) prescribing label §5.1 / §7.1 / Table 2 / Table 4

Spironolactone

  • T6 · FDA PrescribingFDA spironolactone label §7.1 — the potassium-raising co-agents (ACE/ARB/NSAID/trimethoprim/heparin) + salt substitutes
  • T6 · FDA PrescribingFDA spironolactone prescribing label §4 / §5.1 / §7.1 / §17

St John's WortHypericum perforatum

  • T0 · Preliminary (in vitro / animal)Mechanism: hyperforin as a potent PXR (pregnane X receptor) agonist driving CYP3A4 + P-gp induction (Moore 2000, PNAS 97:7500, and the hyperforin/PXR literature)
  • T3 · PubMedHuppertz 2018, Br J Clin Pharmacol 84:2903 (doi 10.1111/bcp.13757, PMID 30192025) — St John's Wort × rivaroxaban, n=12
  • T3 · PubMedJiang 2004, Br J Clin Pharmacol 57:592 (doi 10.1111/j.1365-2125.2003.02051.x, PMID 15089812) — St John's Wort (and ginseng) × warfarin, healthy subjects
  • T4 · NCCIHNCCIH, "St. John's Wort and Depression" (nccih.nih.gov) — efficacy + interaction breadth

TB-500

  • T0 · Preliminary (in vitro / animal)Ho 2012, J Chromatogr A 1265:57 (doi 10.1016/j.chroma.2012.09.043, PMID 23084823) — Hong Kong Jockey Club racing laboratory: identification of TB-500 and metabolites in horses after administration; companion identity paper Esposito 2012 (doi 10.1002/dta.1402, PMID 22962027)
  • T0 · Preliminary (in vitro / animal)Rahaman 2024, J Chromatogr B 1235:124033 (doi 10.1016/j.jchromb.2024.124033, PMID 38382158) — KIST Doping Control Center: TB-500 metabolism in rats + human serum in vitro, with fibroblast wound-healing assay
  • T0 · Preliminary (in vitro / animal)Safer 1991, J Biol Chem 266:4029 (PMID 1999398) — thymosin β4 identified as the major G-actin-sequestering peptide
  • T0 · Preliminary (in vitro / animal)Bock-Marquette 2004, Nature 432:466 (doi 10.1038/nature03000, PMID 15565145) — mouse coronary ligation, full-length Tβ4; companion Smart 2007, Nature 445:177 (PMID 17108969) — epicardial progenitor mobilization
  • T0 · Preliminary (in vitro / animal)Malinda 1999, J Invest Dermatol 113:364 (doi 10.1046/j.1523-1747.1999.00708.x, PMID 10469335) — rat full-thickness wounds, topical or i.p. full-length Tβ4
  • T1 · PubMedGuarnera 2010, Ann N Y Acad Sci 1194:207 (doi 10.1111/j.1749-6632.2010.05490.x, PMID 20536470) — Phase 2 double-blind placebo-controlled dose-escalation, TOPICAL full-length thymosin β4, n=73 venous stasis ulcers
  • T1.5 · Peptide Clinical PracticeMendias & Awan 2026, Sports Med 56:1921 (doi 10.1007/s40279-026-02437-0, PMID 41966639) — clinical review: approved and unapproved peptide therapies for musculoskeletal injuries and athletic performance
  • T3 · PubMedSosne 2015, Cornea 34:491 (doi 10.1097/ICO.0000000000000379, PMID 25826322; NCT01393132) — Phase 2 double-masked RCT, RGN-259 0.1% thymosin β4 EYE DROPS, n=9 severe dry eye
  • T3 · PubMedRuff 2010, Ann N Y Acad Sci 1194:223 (doi 10.1111/j.1749-6632.2010.05474.x, PMID 20536472) — randomized placebo-controlled Phase 1, IV full-length thymosin β4, 40 healthy subjects, single then 14 daily doses of 42–1260 mg
  • T6 · FDA AdvisoryFDA 503A actions on "Thymosin Beta-4, Fragment (LKKTETQ)": Category 2 placement (significant safety risk) Sept 29 2023, same batch as BPC-157 → nomination withdrawn (FDA "may present significant safety risks" page) → PCAC July 23–24 2026 briefing (fda.gov/media/193349): proposed NOT adding TB-500 free base or acetate to the 503A Bulks List

Tranylcypromine

  • T6 · FDA PrescribingFDA tranylcypromine (Parnate) prescribing label §5.2 + Table 5 (tyramine foods)
  • T6 · FDA PrescribingFDA Parnate label §7.2 (mechanism) + boxed warning (serotonergic + tyramine)

Vitamin D3+K2

  • T0 · Preliminary (in vitro / animal)Luo 1997, Nature 386:78 (doi 10.1038/386078a0, PMID 9052783) — MGP-knockout mice; mechanism context: van Ballegooijen 2017 review (PMID 29138634)
  • T1 · PubMedManson 2019 (VITAL, vitamin D arm), N Engl J Med 380:33 (doi 10.1056/NEJMoa1809944, PMID 30415629) — RCT, n=25871, D3 2000 IU/d, median 5.3 y, NIH-funded
  • T1 · PubMedLeBoff 2022 (VITAL fracture ancillary), N Engl J Med 387:299 (doi 10.1056/NEJMoa2202106, PMID 35939577) — n=25871, 1991 fractures
  • T1 · PubMedNeale 2022 (D-Health), Lancet Diabetes Endocrinol 10:120 (doi 10.1016/S2213-8587(21)00345-4, PMID 35026158) — RCT, n=21315 Australians ≥60, 60000 IU MONTHLY × 5 y
  • T1 · PubMedJolliffe 2021, Lancet Diabetes Endocrinol 9:276 (doi 10.1016/S2213-8587(21)00051-6, PMID 33798465) — updated meta-analysis, 43 trials, n=48488, vitamin D and acute respiratory infections
  • T1 · PubMedDiederichsen 2022 (AVADEC), Circulation 145:1387 (doi 10.1161/CIRCULATIONAHA.121.057008, PMID 35465686) — RCT, n=365 men with aortic valve calcification, MK-7 720 µg/d + vitamin D 25 µg/d × 24 mo
  • T1.5 · PubMedDemay 2024, Endocrine Society Clinical Practice Guideline, J Clin Endocrinol Metab 109:1907 (doi 10.1210/clinem/dgae290, PMID 38828931) — vitamin D for disease prevention; companion: USPSTF 2021 (PMID 33847711, I-statement on screening)
  • T2 · NIH ODSNIH ODS Vitamin D Fact Sheet for Health Professionals (ods.od.nih.gov/factsheets/VitaminD-HealthProfessional)
  • T2 · NIH ODSNIH ODS Vitamin K Fact Sheet for Health Professionals (ods.od.nih.gov/factsheets/VitaminK-HealthProfessional)
  • T3 · PubMedSchurgers 2007, Blood 109:3279 (doi 10.1182/blood-2006-08-040709, PMID 17158229) — K1 vs natto-derived MK-7 pharmacokinetics (VitaK group; one NattoPharma-affiliated co-author); companion: Sato 2012 (PMID 23140417 — nutritional-dose MK-4 undetectable in serum)
  • T3 · PubMedKnapen 2013, Osteoporos Int 24:2499 (doi 10.1007/s00198-013-2325-6, PMID 23525894) — RCT, n=244 healthy postmenopausal women, MK-7 180 µg/d × 3 y; NattoPharma sponsorship (verified via trade press; VitaK authors)
  • T3 · PubMedCockayne 2006, Arch Intern Med 166:1256 (doi 10.1001/archinte.166.12.1256, PMID 16801507) — meta-analysis of 7 Japanese MK-4 45 mg/d fracture trials — READ WITH its 2018 correction (JAMA Intern Med 178:875 erratum + Grey/Avenell/Bolland letter)
  • T6 · FDA PrescribingFDA warfarin (Coumadin) prescribing information, §7.5 drug–food interactions; plus 21 CFR 101.72 (authorized health claim: calcium, vitamin D, and osteoporosis)

Warfarin

  • T1 · PubMedSconce 2007, Blood 109:2419 (doi 10.1182/blood-2006-09-049262) — double-blind RCT, 70 unstable AF patients, 150 µg/d oral vitamin K vs placebo, 6 months
  • T1 · PubMedMohammed Abdul 2008, Br J Pharmacol 154:1691 (doi 10.1038/bjp.2008.210, PMID 18516070) — crossover, cranberry AND garlic × warfarin; + Ansell 2009, J Clin Pharmacol 49:824 (cranberry juice RCT, n=30)
  • T3 · PubMedSconce 2005, Thromb Haemost 93:872 (doi 10.1160/TH04-12-0773) — 26 unstable vs 26 stable warfarin patients, food diaries
  • T3 · PubMedJiang 2005, Br J Clin Pharmacol 59:425 (PMID 15801942) — ginkgo + ginger × warfarin; + Nutrients 2016 fish-oil cohort (n=573)
  • T6 · FDA PrescribingFDA warfarin (Coumadin) prescribing label §7.5 (Botanical/Foods) + §17 Medication Guide
  • T6 · FDA PrescribingFDA warfarin label §7.5 — St John's Wort (CYP/VKA inducer context) + §5.9 endogenous factors
09.

Standing references

Regimens' analysis and the Ask Regimens assistant draw on these authoritative sources. They are the evidence base for compounds that do not yet have a per-compound curated citation above.

Last reviewed · October 2026