Oral supplemental or medicinal vitamin B6 exposure × risk of new or worsened clinical sensory neuropathy

Required evidence, verification status and materials actually read
Item	AVerification status	BReading scope	CReview item	DCurrent findings	EWhy unverified	FRequired materials and conditions	GFurther research
1	Met	Full text not readStored summary read	N01 · Safety contractWere the original safety-only designation and the contract that efficacy is not applicable preserved?Required	The original question type is safety and safety_only is true. efficacy_grade/score are not_applicable, efficacy_framework_applied is false, grade is ?, and score is an empty value. axis_notes is an empty object, and the axes/no_human keys are absent. Document quality B is not a harm grade.	The narrow condition for preserving the display was verified. Only the original warning, non-applicability of efficacy, and historical values were retained, with no new risk judgment.	Original safety designation, assessment contract, and document-quality metadata	Compare the display fields with the technical preservation of the original safety/non-efficacy contract.
2	Met	Full text not readStored summary read	N02 · Claim boundariesWas the separate question of oral B6 and new or worsened clinical sensory neuropathy fixed?Required	The archived harm question concerns the risk of new or worsened clinical sensory neuropathy. The main exposure is oral B6 from supplements/medicines in adults; ordinary/fortified foods, parenteral/animal material, and changes in PLP/QST/nerve conduction alone are distinguished separately.	The inclusion/exclusion conditions for the separate harm question were linked to the actual facet. Clinical treatment efficacy or individual risk rates were not newly assessed.	Original claim, population/exposure, route, and endpoint boundaries	Compare the roles of material on other routes, treatment of pre-existing disease, and changes in test results against the eligibility boundaries.
3	Partly verified	Full text not readStored summary read	N03 · Vitamer identityAre the B6 vitamer, salt, and formulation identities established for each source?Required	The preserved manuscript distinguishes pyridoxine, pyridoxine hydrochloride, pyridoxal, PLP/P5P, and pyridoxamine. Although causality is clearest for high-dose pyridoxine, the exact salt in several sources is unverified, and no clinical guarantee that PLP is free of risk was verified. S11 S12 S13 S14 S20 S21 S22	The original boundaries distinguishing vitamers are present, but the salt identities/equivalence of risk of all actual formulations are not established.	Original formulation composition, vitamer/salt, and product description	Compare the reported substance and actual formulation composition by vitamer.
4	Unverified	Full text not readStored summary read	N04 · Product and actual exposureAre the brand, batch, measured content, and actual dose taken verified?Required	Single-ingredient tablets/capsules and combination products are distinguished, but the exact brand, release formulation, purity, batch, measured content versus labeled amount, and actual dosing frequency/total duration are unverified in several sources. These gaps were not filled in as identical formulations or actual total intake. S20 S21 S22 S24 S25	The currently preserved content explicitly states that these detailed identities and actual amounts used cannot be established.	Manufacturing/labeling, batch, measured content, and dosing frequency/adherence records	Review whether product information agrees with individual intake records.
5	Partly verified	Full text not readStored summary read	N05 · Multiple products and unitsCan content per tablet be distinguished from actual total daily intake across multiple products?Required	In the 2018 Lareb abstract, 1.4–100 mg is the content per tablet. Of the TGA's 32 selected reports, 9 involved multiple products. Daily total or cumulative intake was not calculated using unverified dosing frequency/measured amounts and overlapping categories. S11 S21 S22	The units and the signal involving multiple products are known, but components needed to establish individual actual total/cumulative intake are insufficient.	Product-specific content units, dosing frequency/number taken, and concurrent-exposure table	Compare the data units for per-tablet content, per-product content, and total daily intake.
6	Met	Full text not readStored summary read	N06 · Exposure routeWas oral exposure from supplements/medicines separated from other routes/foods?Required	The facets concern B6 from oral supplements/medicines, with ordinary/fortified foods kept as separate exposure strata. Parenteral/animal doses are not extrapolated to human incidence after oral exposure.	The condition preserving the actual route and exposure-source boundaries was verified. New harm from other routes was not assessed.	Original route, exposure source, and applicability of related material	Compare directness/exclusions according to the original route and exposure stratum.
7	Partly verified	Full text not readStored summary read	N07 · Population and baseline statusAre the population, pre-exposure neuropathy, and underlying diseases verified for each source?Required	The 5 healthy volunteers, existing CIAP patients/controls, TB cohort treated with terizidone, and 3 older cases represent different populations. Individual baseline renal/hepatic function, medications, and classification as new onset/worsening of existing disease are unverified in several sources. S20 S23 S24 S25	The main population contexts are available, but there is no material fully verifying individual baseline status/selection and pre-existing neuropathy.	Table of inclusion/exclusion, baseline symptoms, examination/disease, renal/hepatic status, and medications	Review applicability limitations related to baseline risk and population selection.
8	Partly verified	Full text not readStored summary read	N08 · Clinical event definitionWas clinical sensory neuropathy confirmed/ascertained separately from test markers?Required	Clinical new onset/worsening is the primary endpoint, and changes in PLP/QST/nerve conduction alone are excluded. A conflict in the clinical numerator between Berger and EFSA's individual-level extraction and the lack of consistent clinical confirmation in Lareb remain; all participants/reports therefore cannot be treated as equally confirmed events. S14 S20 S21 S22 S25	The boundary between clinical events and test findings is defined, but complete comparability/confirmation of diagnosis and ascertainment across sources is unverified.	Original diagnostic criteria, symptoms/examination, QST/conduction, and detection/blinding procedures	Compare clinical event definitions with differences in measurement/detection of test markers.
9	Unverified	Full text not readStored summary read	N09 · Distinguishing new onset from worseningCan new onset and worsening of pre-existing symptoms be distinguished separately?Required	The original facet labels material unable to separate the outcomes as having a mixed endpoint. Court's 50 people constitute a mixture of new onset/worsening, and the respective event counts were not verified in the abstract. Lareb also has gaps in clinical confirmation and the distinction between new onset/worsening. S21 S22 S25	The current archived material cannot establish all separate event counts and denominators for new onset/worsening.	Table of baseline symptoms, event counts for new onset/worsening, populations at risk, and timing	Trace pre-existing disease and the classification of events before and after exposure.
10	Met	Full text not readStored summary read	N10 · High-dose exposureWere Berger's reported doses separated from observations of onset and after withdrawal?Required	Berger is an uncontrolled prospective exposure study in which 5 volunteers received pyridoxine at 1 or 3 g/day. The preserved account states that symptoms appeared earlier at the higher dose and worsening could continue for 2–3 weeks after withdrawal. Individual cumulative exposure was not calculated. S20 S14	The narrow attribution of reported doses and temporal relationships was verified. Clinical event counts/population incidence remain subject to separate unverified/conflicting conditions.	Original table of dosing/onset and follow-up after withdrawal	Compare dose, time to onset, and the course after exposure withdrawal separately.
11	Conflicting information	Full text not readStored summary read	N11 · Conflict in the clinical numeratorIs Berger's actual number of clinical cases consistently verified across sources?Required	The broad description in Berger's abstract and EFSA's individual-participant extraction disagree on the number of people with onset of clinical symptoms. The EFSA table includes participants with changes in sensory testing alone and no clinical symptoms; therefore, 5/5 or 100% occurrence is not claimed. S20 S14	Descriptions of the same clinical occurrence disagree, so a single numerator cannot be established. This descriptive conflict was not resolved through a new causality judgment.	Correspondence between the original abstract, individual clinical symptom/test table, and EFSA extraction	Review correspondence of participants/clinical criteria across sources and the disagreement in numerators.
12	Met	Full text not readStored summary read	N12 · Actual comparatorWere the uncontrolled design of the high-dose experiment and the boundaries of comparative risk preserved?Required	Berger is a small prospective high-dose exposure study without an unexposed control. The original weight explicitly states that it serves as evidence for causality of high-dose pyridoxine but is not used as population incidence. This table does not convert it into an RCT or an RR for general users. S20 S14	The condition for preserving the actual design and original interpretation limitations was verified. High-dose causality was not newly certified, and comparative risk was not calculated.	Original design, comparator/allocation, and exposure table	Review the scope of causal/risk interpretation permitted by the design and actual comparison conditions.
13	Partly verified	Full text not readStored summary read	N13 · Recovery and rechallengeAre recovery/worsening after withdrawal and the actual course on rechallenge verified?Required	Official assessments include cases of improvement after withdrawal, but the speed/completeness of recovery is not guaranteed. Worsening for 2–3 weeks after withdrawal of high-dose exposure and the possibility of long-term disability are both preserved. Sufficient individual rechallenge data were not verified in this extraction. S14 S20 S24 S26	Some post-withdrawal courses are available, but individual recovery/confirmation through rechallenge and complete follow-up cannot be established.	Original individual event records for withdrawal, follow-up/function, and rechallenge	Compare onset and changes after withdrawal with alternative causes/completeness of follow-up.
14	Partly verified	Full text not readStored summary read	N14 · Overlap within a reporting seriesAre the independence and overlap relationships of Lareb reports verified?Required	The 2025 Lareb analysis includes 224 reports and overlaps within the same series with the 2018 count of 90 reports and EFSA's interim counts. The original evidence groups them under F-LAREB and does not sum them. The current archived summary does not contain a table of independent events with individual report overlap resolved. S21 S22 S14	Overlap within the series is explicitly stated, but no material fully establishes the correspondence of independence/overlap at the individual-report level.	Original report identifiers, collection period, and overlap/re-citation correspondence table	Compare the relationship between reanalysis of the same reports and new independent events.
15	Met	Full text not readStored summary read	N15 · Collection period and reference dateWere the Lareb collection period and the historical reference dates of the material separated?Required	The manuscript's 2025 Lareb analysis covers reports collected from 2007-08 through 2023-12-31, with 224 reports. The original verified_date is 2026-09-15, distinguished from the local archived-summary review date of 2026-10-05 and the actual report collection window. S22	Only the attribution of the original collection period and dates to their events was verified. This did not involve looking up the latest external reports/official regulations.	Original analysis collection window and publication/review metadata	Compare the actual event associated with each date and the applicability of the material.
16	Unverified	Full text not readStored summary read	N16 · Report confirmation and durationAre clinical confirmation, actual exposure duration, and completeness of collection of Lareb reports verified?Required	Lareb provides a safety signal from spontaneously reported neuropathy. The original evidence/manuscript states that consistent clinical confirmation, actual daily amounts/durations, and separation of new from worsened cases are incomplete. Blood values alone do not establish clinical toxicity in each report. S21 S22	The currently retained materials contain no original table that would establish confirmation, actual timing, or completeness of detection for each report.	Original report table of diagnosis/exposure/duration, detection/selection, and follow-up	Review reporting definitions, selection/detection processes, and individual temporal relationships.
17	Unverified	Full text not readStored summary read	N17 · Exposed-person denominator for reportsIs a denominator verified for calculating incidence among exposed persons from spontaneous reports?Required	Lareb’s 224 reports and TGA’s 32 reports are report counts. The manuscript states that incidence is not calculated because an exposed-person denominator and consistent clinical confirmation/duration are absent. This table also calculates neither report proportions nor incidence. S21 S22 S11	Without a population-at-risk denominator and duration, report counts cannot establish incidence among exposed persons.	Data on all exposed persons, observation time by dose, all/confirmed events, and unreported cases	Review the correspondence between report-based counts and the actual population at risk/observation time.
18	Partly verified	Full text not readStored summary read	N18 · TGA selected-report signalCan selection and overlap in TGA’s 32 reports and low-dose/multiple-product categories be verified?Required	Through 2022-08-05, TGA reported 32 selected reports, of which 21 involved 50 mg/day or less and 9 involved use of multiple products. The categories may overlap. These describe the composition of reports, not the probability of occurrence among users at those doses; an individual-level selection/overlap table is absent from the retained archived summaries. S11 S12	The selected report counts/categories and possibility of overlap are known, but the complete selection, confirmation, and overlap correspondence cannot be established.	Original TGA tables of report selection, clinical confirmation, and overlap between dose/multiple-product categories	Compare selection criteria, category overlap, and detection/reporting bias.
19	Unverified	Full text not readStored summary read	N19 · Low-dose causalityAre comparative risk, causality, and a no-risk boundary at low doses established?Required	Low-dose spontaneous reports constitute a possible signal, but a minimum risk dose/duration and an individual no-risk boundary have not been verified. The manuscript avoids both confirming causality at all low doses and declaring all low doses safe, and distinguishes these questions from labeling-warning criteria. S11 S12 S14	Without actual comparative/denominator, exposure, and confirmation data, a causal risk or no-risk boundary applicable to all low doses cannot be established.	Exposure/comparator, event, duration, confounding, and risk-estimate data for each low dose	Distinguish the evidentiary level of spontaneous-report signals from that of comparative-risk/causal conclusions.
20	Partly verified	Full text not readStored summary read	N20 · TB comparative estimateAre the dose-specific comparative estimate and its uncertainty in the tuberculosis cohort verified?Required	Court is a terizidone-treatment cohort with 144 people recruited and neuropathy in 50 people (35% in the original). The comparison of 200 versus 150 mg/day retains an adjusted HR of 2.79, P = 0.01, for a mixed new/worsened endpoint. Group-specific denominators/event counts, the HR CI, and exact follow-up duration were not verified from the abstract. S25	The nominal-dose comparison and reported HR/P are available, but group-specific denominators and CI/duration are insufficient. No new CI/RR/proportion was calculated.	Tables of exposure/events, denominators, adjustment models, HR/CI, and follow-up by dose group	Compare estimates and uncertainty for the same event/comparator/duration and analysis model.
21	Met	Full text not readStored summary read	N21 · TB nonrandomized designWere the nonrandomized doses in the tuberculosis cohort and limitations on application to general supplement use preserved?Required	The original design is a prospective cohort of multidrug-resistant tuberculosis treated with terizidone; B6 doses are nonrandomized. HIV, tuberculosis, co-medications, and prescribing reasons are intertwined, so the retained HR is not transferred to a causal RR for general supplement users. S25	The condition of preserving the actual nonrandomized context and original generalizability limitations was verified. This is not a judgment that confounding was eliminated.	Original recruitment/prescribing, population/concurrent treatment, and actual comparator design	Review the interpretive scope arising from the population, prescribing context, and nonrandomized comparison.
22	Unverified	Full text not readStored summary read	N22 · TB alternative explanationsWas confounding by tuberculosis/HIV, medications, and prescribing reasons sufficiently controlled?Required	The manuscript retains the intertwined roles of HIV, TB, co-medications, and prescribing reasons. The reported HR was verified in the abstract, but all adjustment variables, baseline neuropathy, prescribing/adherence, and disease roles cannot be established from the retained archived summaries. S25	Adjustment tables and actual baseline/prescribing data are insufficient to establish the extent of control for alternative causes other than B6.	Original adjustment-model, prescribing/underlying-disease, medication, and exposure-follow-up data	Review actual measurement of adjustment variables and confounding associated with timing and prescribing.
23	Partly verified	Full text not readStored summary read	N23 · TB endpoint and time denominatorCan the endpoint/time denominator for TB neuropathy be separated from other neuropsychiatric AE?Required	Court’s outcome is a mixture of new or worsened peripheral neuropathy. Separate event counts and exact follow-up duration are unverified in the abstract. The person-month incidence of all neuropsychiatric AE was not used as the incidence of this clinical sensory neuropathy. S25	Boundaries for the mixed endpoint and exclusion of other AE are present, but event-specific definitions, separate counts/time, and participant flow are incomplete.	Neuropathy-specific tables of definitions/confirmation, events/time, and missing data/discontinuation	Compare attribution of the mixed endpoint, other AE, and observation time/participant flow.
24	Met	Full text not readStored summary read	N24 · CIAP population applicabilityWas pre-existing disease in the CIAP case-control study distinguished from the question of new toxicity?Required	Visser is a case-control study of 381 patients with pre-existing CIAP and 140 healthy controls. The original endpoint concerns an association with pre-existing disease, not incident toxicity. The original weight is preserved as limiting/contrary evidence and is not used as a causal incidence rate or a safety guarantee. S23	The population/design for the association with pre-existing disease and the boundary against transferring it directly to new-onset risk were verified.	Original population/design, baseline symptoms, and exposure timing/endpoints	Compare the directness of the prevalent-case case-control study for the new-onset question and assess reverse causation.
25	Met	Full text not readStored summary read	N25 · Attribution of contrasting resultsWere the nonsignificant blood-value result and the supplement-use association in CIAP both preserved?Required	In CIAP, the difference in median blood B6 values of 99 versus 109 nmol/L was nonsignificant at P = 0.58. Supplement use was 31% versus 22%, OR 1.7 (95% CI 1.0–2.7; P = 0.032). Considering daily amounts, cumulative amounts, duration, and blood values, the authors interpreted a causal association as unlikely. Both contrasting and limiting results are preserved. S23 S14	Reported values, attribution to different exposures/markers, and the authors’ limiting interpretation were linked together. No new causality/no-risk assessment was performed.	Original results tables, blood-value/supplement-use estimates, and authors’ interpretation	Compare the results, directions, and uncertainties for different measurements/exposures separately.
26	Unverified	Full text not readStored summary read	N26 · Reverse causation and underlying causesAre reverse causation and alternative causes in CIAP and reports sufficiently verified?Required	The manuscript retains possible reverse causation from supplement use prompted by CIAP symptoms and the selected phenotype. Other causes, including diabetes, B12 deficiency, alcohol, kidney disease, and anticancer/TB medications, also need to be considered. Whether these alternatives were sufficiently excluded in each source is unverified. S23 S14 S21 S22 S25	Specific data on temporal order/baseline status and alternative causes are insufficient to establish elimination of reverse causation/confounding.	Baseline symptoms, start/sequence of use, examinations/other tests, and alternative diseases/medications	Review reverse causation/confounding associated with exposure timing and disease selection/detection.
27	Partly verified	Full text not readStored summary read	N27 · Older-adult combination-product casesCan the combination product and actual long-term exposure in 3 older adults be verified?Required	Kulkantrakorn is a case series of people aged 80·83·83 years, 3 in total, with sensory ataxic neuropathy/gait impairment. They used pyridoxine in B1/B6/B12 combination tablets at 600 mg/day for 3–10 years. The exact formulation, actual cumulative amount, and all underlying causes cannot be established from the current extraction. S24	The population, combination/nominal dose, and duration are available, but verification of detailed product information, actual use, and underlying causes is insufficient.	Original case-specific product/composition, dose/duration, baseline-status, and adherence data	Compare actual exposure in each case and the combination-product/older-adult context.
28	Partly verified	Full text not readStored summary read	N28 · Long-term residual disabilityAre individual recovery/disability assessments and long-term follow-up in the older-adult cases sufficiently verified?Required	The 3 older-adult cases were reported to show no significant improvement in neuropathy or gait even 2 years after withdrawal. The original weight is a warning of possible persistent harm and explicitly states that a probability of permanent damage cannot be calculated. Verification of complete individual assessments/follow-up data beyond the abstract is insufficient. S24	The course is reported, but follow-up, denominator, and assessment data to establish individual probabilities of permanent damage/recovery are absent.	Original withdrawal/follow-up, neurological/gait assessments, alternative causes, and long-term denominators	Review recovery speed/completeness and limitations of follow-up and alternative-cause assessment.
29	Unverified	Full text not readStored summary read	N29 · Unacquired candidatesAre the original results of candidates concerning recovery, absence of neuropathy, and high doses verified?Required	The recovery case S26, the title concerning absence of neuropathy during homocystinuria treatment S27, and pyridoxine abuse S28 are retained as candidates whose original full texts/complete abstracts were not acquired. Quantitative values, safety, and causality were not filled in from titles/metadata alone, and the captcha/fetch failures at that time are not relabeled as failures during this task. S26 S27 S28	The retained archived summaries lack sufficient abstracts/full texts to verify original clinical results, exposure, and denominators.	S26/S27/S28 original abstracts/full texts and case/results tables	Compare candidate identity/access scope with the feasibility of extracting actual original results.
30	Unverified	Full text not readStored summary read	N30 · Adjacent treatment evidenceCan original observations for this harm endpoint be traced in copies of the same Levin paper?Required	S01/S02 refer to The influence of pyridoxine in diabetic peripheral neuropathy with the same DOI 10.2337/diacare.4.6.606 and PMID 6751736. The original citation records abstract/author-copy access locations, but the 6 evidence entries in the current source lack a detailed array of this paper’s harm events, denominators, and exposures. Figures from another efficacy manuscript were not borrowed. S01 S02	Only the same-bibliography relationship is verified; the original observations/denominators for this clinical harm endpoint cannot be established from the currently archived summaries.	Tables of actual harm events, baseline status/exposure, and denominators/durations in that paper	Compare the copy/abstract relationship and the scope for direct extraction of these new/worsened clinical events.
31	Met	Full text not readStored summary read	N31 · Roles of official documentsWere official assessments and re-citations excluded from counts of new independent human trials?Required	The original evidence distinguishes 6 families: Berger/Lareb/TGA/Visser/Kulkantrakorn/Court. EFSA cites Berger and Lareb again; NIH provides official background, and TGA provides selected-report/regulatory documents. S01/S02 copies of the same paper and official documents are not added together as independent trials. S01 S02 S11 S12 S13 S14 S20 S21 S22	The condition of preserving the roles of documents/copies and report families was verified. The 6 families were not declared to be 6 independent clinical trials or a count of confirmed events.	Citation lineage in the original official documents, underlying reports, and native family/linked-source lists	Trace re-citations/reanalyses of original experiments/reports and the roles of official documents.
32	Unverified	Full text not readStored summary read	N32 · Overall comparative riskAre comparative risk, CI, and background risk applicable to all users verified?Required	The original assessment supports causality for high-dose pyridoxine but states that the risk rate among all users is unverified. Spontaneous reports lack an exposed-person denominator, and the TB HR/CIAP OR have separate contexts. No overall RR/RD/incidence, CI, NNH, or pooled estimate is calculated. S20 S21 S22 S23 S25	There are no data establishing comparisons, denominators/durations, and risk estimates for all users addressing the same question.	Actual exposed/unexposed, event/denominator, follow-up, RR/RD/CI, and background-risk data	Review the applicability of estimates, uncertainty, and absolute risk by population/formulation/duration.
33	Unverified	Full text not readStored summary read	N33 · Vulnerable groups and long-term applicabilityAre form-specific long-term risks in vulnerable groups and pre-existing neuropathy verified?Required	Form-specific toxicity incidence/individual safe doses have not been verified in renal or hepatic impairment, pregnancy/lactation, children, or pre-existing neuropathy. Low B6 indicators in renal disease are not converted into high-dose safety, and contexts requiring a separate treatment benefit–risk assessment are preserved. S13 S14 S24 S26 S27	The manuscript explicitly identifies gaps in actual population-specific incidence/doses and long-term evidence.	Population-specific formulation, baseline status, exposure, long-term event/follow-up, and treatment-context data	Review special populations/treatment contexts and the applicability of existing evidence.
34	Unverified	Full text not readStored summary read	N34 · Minimum risk and cumulative exposureAre the minimum risk dose/duration, individual no-risk boundary, and cumulative exposure established?Required	An established minimum risk dose/duration and individual no-risk boundary have not been verified. Individual actual daily doses, duration, and adherence were insufficiently documented, so cumulative intake was not calculated in the manuscript either. This table creates no new conversions or minimum safety/risk thresholds. S14 S20 S21 S22	The actual components and comparative risk data needed to establish a threshold or cumulative exposure are unavailable.	Individual measured amounts/doses, duration/adherence, events, and comparison/denominator data	Review the actual links between dose, duration, cumulative exposure, and onset/background risk.
35	Met	Full text not readStored summary read	N35 · Nutritional upper intake levelsHave the jurisdictions/purposes of the FNB/EFSA upper intake levels been distinguished from clinical toxicity thresholds?Supporting	The preserved FNB adult UL is 100 mg/day, and the EFSA adult UL is 12 mg/day; these also apply to pregnant/lactating adults. The jurisdictions and assessment methods differ, and the values are not therapeutic dose recommendations, clinical toxicity thresholds, or guarantees of no risk below them. The latest official regulations were not looked up in this review. S13 S14	The preserved upper intake values and the condition for distinguishing jurisdictions/purposes were verified. This was not an assessment of new regulations or individual safety.	Preserved FNB/EFSA editions, populations/risk assessments, and basis for UL derivation	Compare jurisdictions/purposes, editions/populations, and the roles of clinical risk evidence.
36	Met	Full text not readStored summary read	N36 · Label warning rulesHave TGA label warnings been distinguished from biological risk boundaries?Supporting	The manuscript records Australia's label warning for supplemental medicines providing daily B6 >10 mg and the 2023-03-01 transition deadline. These are preserved as labeling rules in force on 2026-09-15 and are not turned into a biological boundary at which risk begins or a new regulatory lookup in this review. S11	The boundaries of the original labeling/date records and the prohibition on repurposing them as clinical thresholds were verified.	Preserved TGA label warning sections, transition/application dates, and products covered	Distinguish the roles and dates of administrative labeling and clinical risk evidence.
37	Met	Full text not readStored summary read	N37 · Future sales classificationHas the future TGA sales classification been distinguished from current prescription/labeling rules?Supporting	Australia's transition to pharmacist control for products providing more than 50 mg/day–up to and including 200 mg/day is scheduled for 2027-06-01 and was a future regulation as of 2026-09-15. It is distinguished from prescription control above 200 mg/day. Labeling/sales/nutritional ULs are different rules and are not clinical toxicity boundaries. S12	The purposes and date attribution of the original scheduled/current rules were distinguished. Their implementation/latest status was not looked up in this review.	Preserved TGA sections on sales classification/effective dates and products covered	Compare current/future application dates and the purposes of sales, labeling, and nutritional criteria.
38	Partly verified	Full text not readStored summary read	N38 · Funding and rolesIs the actual scope of verification of funding, product supply, and conflicts of interest known for each report?Required	Lareb 2018 includes a statement of no funding for preparation, while the complete funding for 2025 is unverified. For Visser, only EFSA's mention of foundation support is available, and verification of the original roles is insufficient. Court's PubMed record indexes NIH/NIAID·Wellcome support, but the complete sponsor roles/product supply are unverified. Funding for Berger and the elderly cases is also unverified. S20 S21 S22 S23 S24 S25	Some declarations/indexing and official activities are documented, but material establishing the complete funding/supply/roles for each report is unavailable.	Original funding/COI, product supply, and design/analysis/reporting role declarations	Compare each report's support/declarations with the scope of verification of actual research/product roles.
39	Unverified	Full text not readStored summary read	N39 · Advance plans and search scopeIs the actual scope of verification of registration, plans, and corrections/retractions sufficiently established?Required	The registry_id values in the 15 citations are empty, and the manuscript limits registration/correction/retraction searches to the recorded scope. The manuscript states that detailed search/access/selection records are in the delivery package, but the ZIP/separate logs referred to there were not read in the review described in that record. No new determination is made that registration is absent or that the entire literature has integrity. S20 S21 S22 S23 S24 S25	The currently preserved archived summaries alone cannot establish the full scope of plans/registration or actual detailed search and change/correction/retraction verification.	Registration, protocol/SAP, changes, and correction/retraction search logs/original publication records	Compare advance plans/changes and original reports with the scope of searches/access.
40	Met	Full text not readStored summary read	N40 · Distinguishing reading and datesHave the current summary reading, historical access to originals, and review/access dates been distinguished?Required	The KO/EN text, 6 evidence entries/15 bibliographic entries, assessments, and metadata in the current source were actually read. Access to all external originals/official pages, registrations, and old separate files was not attempted, and these were not acquired or read in this review. Historical access_level/location remain unchanged; individual access-date keys are absent, leaving empty values, and the original verified_date 2026-09-15 is distinguished solely as the review date. S01 S02 S11 S12 S13 S14 S20 S21 S22 S23 S24 S25 S26 S27 S28	The narrow record condition distinguishing actual local reading in this review from historical/external unread materials and dates was verified.	Original bytes of the currently preserved archived summaries, citation access locations/identities, and access-date records	Compare material types, original locations, historical/current reading events, and dates.
41	Met	Full text not readStored summary read	N41 · Personal treatment boundaryHas the original safety warning been kept from becoming personal treatment/discontinuation instructions?Required	The original document explicitly states that it does not provide personal treatment/dosing instructions. For new tingling, burning, reduced sensation, or balance problems, it advises assessment of all products/other causes and preserves the original wording against unnecessary self-directed dose escalation or arbitrary discontinuation/replacement of prescribed treatment. This table creates no new clinical instructions. S11 S12 S13 S14	Only the boundaries of the preserved information were verified; individual doses, discontinuation, or treatment were not assessed.	Original safety warning and personal application/treatment boundary	Compare the boundary between public informational statements and personal treatment instructions with the actual original values.

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41 itemsWhat the statuses mean

Assessment scope

Stored-material review date: 2026-10-05
Original evidence date: 2026-09-15
Scope actually checked: Archived Korean and English manuscripts and case-specific condition and application records. Full papers, supplements, registrations, plans and original data were not read.
What the dates mean: This is the date the archived material was checked, not the date of a search for the latest clinical literature.
Population: Primarily adults with oral B6 exposure; healthy volunteers, people with pre-existing neuropathy, tuberculosis/HIV, and older cases are distinguished. Individual risk rates in children, pregnancy, and kidney disease are unverified
Ingredient, formulation and route: Vitamin B6 exposure: pyridoxine, pyridoxine hydrochloride, pyridoxal, PLP/P5P, and pyridoxamine are distinguished by form; causality is clearest for high-dose pyridoxine · Oral exposure. Parenteral or animal dosing is not extrapolated to human incidence after oral exposure · Single-ingredient tablets/capsules and combination products are distinguished. Exact salt, brand, release formulation, purity, and batch are unverified in many cases; these are not treated as identical formulations
Dose: Exposure is preserved by study, without combining it into a general risk dose. Low-dose reports and high-dose experiments are distinguished; total amounts and measured verification of labeled amounts remain unverified when not established
Comparator: Comparisons with no exposure or lower exposure are prioritized. Uncontrolled experiments and spontaneous reports have no comparator; the CIAP case-control study and tuberculosis dose comparison have separate contexts
Measured outcome: New or worsened clinical sensory neuropathy. Studies unable to separate these outcomes are labeled as having a mixed endpoint; changes in PLP/QST/nerve conduction alone are excluded
Duration: Onset, duration of use, and follow-up after withdrawal are distinguished by study. The minimum duration associated with risk at low doses and several individual exposure durations are unverified
Questions outside this scope: Excluded are changes in test markers alone; efficacy for treatment of pre-existing disease/attributing neuropathy from all causes to the exposure; conversion of report counts into incidence rates; claims of no risk for all vitamers/low doses; and conversion of regulatory criteria into biological thresholds/personal doses.

Evidence and sources

The links below lead to the sources. A link alone does not mean the original source was read or its latest publication status verified.

S01 · The influence of pyridoxine in diabetic peripheral neuropathy

Source

Material type: Original-paper abstract/bibliographic record (historical access)
Materials actually read: The relevant Korean/English summaries and bibliographic records in the archived manuscript were read. The linked external original materials were not read in this review.
Findings recorded in the stored summary: Record at the time of preservation: This is the abstract bibliographic record for the Levin paper, DOI 10.2337/diacare.4.6.606·PMID 6751736. It is the same paper as S02, and the current 6 evidence entries do not preserve this paper's details on new/worsened harm events, denominators, doses, or duration. Values from the adjacent efficacy assessment are not borrowed.
Record level: This is content recorded in the archived manuscript. It is not the result of a new comparison with current external original materials.
Study overlap and independent replication: Independent replication is unverified.

Public availability, access and reading status by material
Material	Public availability	Access status	Actually read	Notes
PubMed original-paper abstract and bibliographic record	Unverified (no external lookup in this review)	Access not attempted	Unread	Limited to the preserved identity/access records and the required material type. External existence/public availability was not newly verified in this review. Only the relevant content, evidence, and bibliography in the currently preserved archived source summary were read. The external material concerned was not read in this review. Only the extent to which the original citation records access to this physical material itself is preserved. Historical access dates for each material are unverified. The archived manuscript review date 2026-09-15 is not the access date of this original material file. Historical access level of this material itself: primary_abstract. Historical location in the reference bibliography: Abstract; Diabetes Care 4(6):606-609 Bibliographic access records are not inherited as access to a separate full text or underlying material. This does not mean that external original materials were acquired or full texts read in this review.
Separate original-paper PDF full text (exact URL/actual historical access unverified)	Unverified (no external lookup in this review)	Access not attempted	Unread	Limited to the preserved identity/access records and the required material type. External existence/public availability was not newly verified in this review. Only the relevant content, evidence, and bibliography in the currently preserved archived source summary were read. The external material concerned was not read in this review. Historical access to the included bibliography/abstract and metadata provides reference context. It is not inherited as the actual access level of a separate original text or underlying material. Historical access dates for each material are unverified. The archived manuscript review date 2026-09-15 is not the access date of this original material file. Historical access level of this material itself: Unverified. Historical location in the reference bibliography: Abstract; Diabetes Care 4(6):606-609 Bibliographic access records are not inherited as access to a separate full text or underlying material. This does not mean that external original materials were acquired or full texts read in this review.

S02 · Levin 1981: author-deposited full-text rendering

Source

Material type: ResearchGate author-deposited full-text HTML (historical access)
Materials actually read: The relevant Korean/English summaries and bibliographic records in the archived manuscript were read. The linked external original materials were not read in this review.
Findings recorded in the stored summary: Record at the time of preservation: The original access_level is author_deposited_full_text_html, and historical locations in Subjects/Methods·Results/Symptoms·Discussion are recorded. What was read in this review was the citation and the related archived source summary; this external copy/its numerical results were not newly read.
Record level: This is content recorded in the archived manuscript. It is not the result of a new comparison with current external original materials.
Study overlap and independent replication: Independent replication is unverified.

Public availability, access and reading status by material
Material	Public availability	Access status	Actually read	Notes
ResearchGate author-deposited full-text HTML	Unverified (no external lookup in this review)	Access not attempted	Unread	Limited to the preserved identity/access records and the required material type. External existence/public availability was not newly verified in this review. Only the relevant content, evidence, and bibliography in the currently preserved archived source summary were read. The external material concerned was not read in this review. Only the extent to which the original citation records access to this physical material itself is preserved. Historical access dates for each material are unverified. The archived manuscript review date 2026-09-15 is not the access date of this original material file. Historical access level of this material itself: author_deposited_full_text_html. Historical location in the reference bibliography: pp606-607 Subjects and Methods; Study protocol; p607 Results/Symptoms; p608 Discussion. Web text lines199-263,323-365,395-437,615-655 Bibliographic access records are not inherited as access to a separate full text or underlying material. This does not mean that external original materials were acquired or full texts read in this review.

S11 · Peripheral neuropathy with supplementary vitamin B6 (pyridoxine)

Source

Material type: TGA official safety web document (historical access)
Materials actually read: The relevant Korean/English summaries and bibliographic records in the archived manuscript were read. The linked external original materials were not read in this review.
Findings recorded in the stored summary: Record at the time of preservation: Through 2022-08-05, 32 reports were selected; 21 involved 50 mg/day or less, and 9 involved multiple products, so the categories may overlap. The daily B6 >10 mg label warning and 2023-03-01 transition are administrative rules. Incidence among exposed users/minimum risk doses are not calculated.
Record level: This is content recorded in the archived manuscript. It is not the result of a new comparison with current external original materials.
Study overlap and independent replication: Independent replication is unverified.

Public availability, access and reading status by material
Material	Public availability	Access status	Actually read	Notes
TGA official safety web full text	Unverified (no external lookup in this review)	Access not attempted	Unread	Limited to the preserved identity/access records and the required material type. External existence/public availability was not newly verified in this review. Only the relevant content, evidence, and bibliography in the currently preserved archived source summary were read. The external material concerned was not read in this review. Only the extent to which the original citation records access to this physical material itself is preserved. Historical access dates for each material are unverified. The archived manuscript review date 2026-09-15 is not the access date of this original material file. Historical access level of this material itself: official_full_html. Historical location in the reference bibliography: Background and review of 32 reports through 2022-08-05; listed-medicine label threshold >10 mg/day; transition 2023-03-01; product forms Bibliographic access records are not inherited as access to a separate full text or underlying material. This does not mean that external original materials were acquired or full texts read in this review.

S12 · Medicines containing vitamin B6 (pyridoxine, pyridoxal or pyridoxamine)

Source

Material type: TGA official medicine safety web document (historical access)
Materials actually read: The relevant Korean/English summaries and bibliographic records in the archived manuscript were read. The linked external original materials were not read in this review.
Findings recorded in the stored summary: Record at the time of preservation: The transition to pharmacist control above 50 mg/day–up to and including 200 mg/day is scheduled for 2027-06-01 and was a future regulation at the original reference date 2026-09-15. It is distinguished from prescription control above 200 mg/day. The original location records published2026-02-19/updated2026-04-07; these are not actual access dates.
Record level: This is content recorded in the archived manuscript. It is not the result of a new comparison with current external original materials.
Study overlap and independent replication: Independent replication is unverified.

Public availability, access and reading status by material
Material	Public availability	Access status	Actually read	Notes
TGA official safety/sales classification web full text	Unverified (no external lookup in this review)	Access not attempted	Unread	Limited to the preserved identity/access records and the required material type. External existence/public availability was not newly verified in this review. Only the relevant content, evidence, and bibliography in the currently preserved archived source summary were read. The external material concerned was not read in this review. Only the extent to which the original citation records access to this physical material itself is preserved. Historical access dates for each material are unverified. The archived manuscript review date 2026-09-15 is not the access date of this original material file. Historical access level of this material itself: official_full_html. Historical location in the reference bibliography: Summary and What health professionals should do, lines195-210; published2026-02-19, updated2026-04-07 Bibliographic access records are not inherited as access to a separate full text or underlying material. This does not mean that external original materials were acquired or full texts read in this review.

S13 · Vitamin B6: Fact Sheet for Health Professionals

Source

Material type: NIH ODS official professional web commentary (historical access)
Materials actually read: The relevant Korean/English summaries and bibliographic records in the archived manuscript were read. The linked external original materials were not read in this review.
Findings recorded in the stored summary: Record at the time of preservation: The manuscript distinguishes the FNB adult UL of 100 mg/day from the EFSA 12 mg/day value by jurisdiction/purpose. It uses general background on impaired renal function/interactions and harm, and does not turn nutritional upper intake levels into therapeutic dose recommendations, clinical thresholds, or no-risk guarantees.
Record level: This is content recorded in the archived manuscript. It is not the result of a new comparison with current external original materials.
Study overlap and independent replication: Independent replication is unverified.

Public availability, access and reading status by material
Material	Public availability	Access status	Actually read	Notes
NIH ODS official professional web full text	Unverified (no external lookup in this review)	Access not attempted	Unread	Limited to the preserved identity/access records and the required material type. External existence/public availability was not newly verified in this review. Only the relevant content, evidence, and bibliography in the currently preserved archived source summary were read. The external material concerned was not read in this review. Only the extent to which the original citation records access to this physical material itself is preserved. Historical access dates for each material are unverified. The archived manuscript review date 2026-09-15 is not the access date of this original material file. Historical access level of this material itself: official_full_html. Historical location in the reference bibliography: Introduction; Individuals with Impaired Renal Function; Health Risks; Table3; Interactions with Medications Bibliographic access records are not inherited as access to a separate full text or underlying material. This does not mean that external original materials were acquired or full texts read in this review.

S14 · Scientific opinion on the tolerable upper intake level for vitamin B6

Source

Material type: EFSA official risk assessment HTML (historical access)
Materials actually read: The relevant Korean/English summaries and bibliographic records in the archived manuscript were read. The linked external original materials were not read in this review.
Findings recorded in the stored summary: Record at the time of preservation: EFSA cites the Berger individual-participant table and the Lareb reporting series again. The discrepancy with the Berger abstract in the clinical-symptom numerator and the participants with test changes alone are preserved. The adult UL of 12 mg/day is a nutritional risk assessment criterion, not a no-risk boundary for all low doses or a clinical toxicity threshold.
Record level: This is content recorded in the archived manuscript. It is not the result of a new comparison with current external original materials.
Study overlap and independent replication: Independent replication is unverified.

Public availability, access and reading status by material
Material	Public availability	Access status	Actually read	Notes
EFSA official risk assessment full-text HTML and Appendix tables	Unverified (no external lookup in this review)	Access not attempted	Unread	Limited to the preserved identity/access records and the required material type. External existence/public availability was not newly verified in this review. Only the relevant content, evidence, and bibliography in the currently preserved archived source summary were read. The external material concerned was not read in this review. Only the extent to which the original citation records access to this physical material itself is preserved. Historical access dates for each material are unverified. The archived manuscript review date 2026-09-15 is not the access date of this original material file. Historical access level of this material itself: official_full_html. Historical location in the reference bibliography: Sections 3.6.1 and 3.6.1.1; human evidence and nutrivigilance; uncertainty; Appendix D.1.1 Berger table; derivation of adult UL Bibliographic access records are not inherited as access to a separate full text or underlying material. This does not mean that external original materials were acquired or full texts read in this review.

S20 · Dose response, coasting, and differential fiber vulnerability in human toxic neuropathy: a prospective study of pyridoxine neurotoxicity

Source

Material type: Original-paper abstract (historical access)
Materials actually read: The relevant Korean/English summaries and bibliographic records in the archived manuscript were read. The linked external original materials were not read in this review.
Findings recorded in the stored summary: Record at the time of preservation: This was prospective, uncontrolled exposure of 5 volunteers to pyridoxine at 1 or 3 g/day. Earlier onset at the higher dose and worsening for 2–3 weeks after withdrawal were reported, but the abstract/EFSA clinical numerators do not agree, so neither 5/5 nor population incidence is claimed.
Record level: This is content recorded in the archived manuscript. It is not the result of a new comparison with current external original materials.
Study overlap and independent replication: Independent replication is unverified.

Public availability, access and reading status by material
Material	Public availability	Access status	Actually read	Notes
PubMed original-paper abstract and bibliographic record	Unverified (no external lookup in this review)	Access not attempted	Unread	Limited to the preserved identity/access records and the required material type. External existence/public availability was not newly verified in this review. Only the relevant content, evidence, and bibliography in the currently preserved archived source summary were read. The external material concerned was not read in this review. Only the extent to which the original citation records access to this physical material itself is preserved. Historical access dates for each material are unverified. The archived manuscript review date 2026-09-15 is not the access date of this original material file. Historical access level of this material itself: primary_abstract. Historical location in the reference bibliography: Abstract; Neurology 1992;42(7):1367-1370 Bibliographic access records are not inherited as access to a separate full text or underlying material. This does not mean that external original materials were acquired or full texts read in this review.
Separate original-paper PDF full text (exact URL/actual historical access unverified)	Unverified (no external lookup in this review)	Access not attempted	Unread	Limited to the preserved identity/access records and the required material type. External existence/public availability was not newly verified in this review. Only the relevant content, evidence, and bibliography in the currently preserved archived source summary were read. The external material concerned was not read in this review. Historical access to the included bibliography/abstract and metadata provides reference context. It is not inherited as the actual access level of a separate original text or underlying material. Historical access dates for each material are unverified. The archived manuscript review date 2026-09-15 is not the access date of this original material file. Historical access level of this material itself: Unverified. Historical location in the reference bibliography: Abstract; Neurology 1992;42(7):1367-1370 Bibliographic access records are not inherited as access to a separate full text or underlying material. This does not mean that external original materials were acquired or full texts read in this review.

S21 · Vitamin B6 in Health Supplements and Neuropathy: Case Series Assessment of Spontaneously Reported Cases

Source

Material type: Publisher abstract and funding/COI declarations (historical access)
Materials actually read: The relevant Korean/English summaries and bibliographic records in the archived manuscript were read. The linked external original materials were not read in this review.
Findings recorded in the stored summary: Record at the time of preservation: The 2018 reports, totaling 90, overlap with the subsequent 224 reports in the same Lareb reporting series. The 1.4–100 mg range is the content per tablet, not actual total daily intake/a threshold. A declaration of no funding for preparation was recorded, but gaps in the exposed-user denominator, clinical confirmation, and duration of the reports remain.
Record level: This is content recorded in the archived manuscript. It is not the result of a new comparison with current external original materials.
Study overlap and independent replication: Independent replication is unverified.

Public availability, access and reading status by material
Material	Public availability	Access status	Actually read	Notes
Publisher original-paper abstract and Funding/COI declaration HTML	Unverified (no external lookup in this review)	Access not attempted	Unread	Limited to the preserved identity/access records and the required material type. External existence/public availability was not newly verified in this review. Only the relevant content, evidence, and bibliography in the currently preserved archived source summary were read. The external material concerned was not read in this review. Only the extent to which the original citation records access to this physical material itself is preserved. Historical access dates for each material are unverified. The archived manuscript review date 2026-09-15 is not the access date of this original material file. Historical access level of this material itself: primary_abstract_and_declarations. Historical location in the reference bibliography: Abstract Methods/Results/Conclusion; declarations Funding and Conflicts; Drug Safety 2018;41:859-869 Bibliographic access records are not inherited as access to a separate full text or underlying material. This does not mean that external original materials were acquired or full texts read in this review.
Separate original-paper PDF full text (exact URL/actual historical access unverified)	Unverified (no external lookup in this review)	Access not attempted	Unread	Limited to the preserved identity/access records and the required material type. External existence/public availability was not newly verified in this review. Only the relevant content, evidence, and bibliography in the currently preserved archived source summary were read. The external material concerned was not read in this review. Historical access to the included bibliography/abstract and metadata provides reference context. It is not inherited as the actual access level of a separate original text or underlying material. Historical access dates for each material are unverified. The archived manuscript review date 2026-09-15 is not the access date of this original material file. Historical access level of this material itself: Unverified. Historical location in the reference bibliography: Abstract Methods/Results/Conclusion; declarations Funding and Conflicts; Drug Safety 2018;41:859-869 Bibliographic access records are not inherited as access to a separate full text or underlying material. This does not mean that external original materials were acquired or full texts read in this review.

S22 · Impact of Regulatory Action on Dose Maximalization for Vitamin B6 Dietary Supplements on the Reporting Pattern for Neuropathy

Source

Material type: Publisher original-paper full-text HTML (historical access)
Materials actually read: The relevant Korean/English summaries and bibliographic records in the archived manuscript were read. The linked external original materials were not read in this review.
Findings recorded in the stored summary: Record at the time of preservation: For the reporting collection window 2007-08–2023-12-31, this is an analysis of 224 reports, overlapping with the earlier 2018 series of 90 reports/EFSA interim counts. Actual daily doses/duration, clinical confirmation, and the exposed-user denominator are insufficient, so incidence is not calculated. The complete funding declaration is unverified.
Record level: This is content recorded in the archived manuscript. It is not the result of a new comparison with current external original materials.
Study overlap and independent replication: Independent replication is unverified.

Public availability, access and reading status by material
Material	Public availability	Access status	Actually read	Notes
Publisher original-paper full-text HTML	Unverified (no external lookup in this review)	Access not attempted	Unread	Limited to the preserved identity/access records and the required material type. External existence/public availability was not newly verified in this review. Only the relevant content, evidence, and bibliography in the currently preserved archived source summary were read. The external material concerned was not read in this review. Only the extent to which the original citation records access to this physical material itself is preserved. Historical access dates for each material are unverified. The archived manuscript review date 2026-09-15 is not the access date of this original material file. Historical access level of this material itself: primary_full_html. Historical location in the reference bibliography: Abstract; Methods case selection; Results; Discussion paragraphs on earlier 90 reports, no exposed denominator, unknown duration; COI; 2025;34:e70108 Bibliographic access records are not inherited as access to a separate full text or underlying material. This does not mean that external original materials were acquired or full texts read in this review.

S23 · Chronic idiopathic axonal polyneuropathy and vitamin B6: a controlled population-based study

Source

Material type: Publisher original-paper abstract (historical access)
Materials actually read: The relevant Korean/English summaries and bibliographic records in the archived manuscript were read. The linked external original materials were not read in this review.
Findings recorded in the stored summary: Record at the time of preservation: Among 381 people with pre-existing CIAP and 140 controls, the median blood concentrations were 99 versus 109 nmol/L, with P=0.58. Supplement use was 31% versus 22%, OR 1.7 (95% CI 1.0–2.7; P=0.032), and the authors interpreted a causal relationship as unlikely. Reverse causation/selection are retained, and these findings are not used as new-onset incidence rates or a no-risk guarantee.
Record level: This is content recorded in the archived manuscript. It is not the result of a new comparison with current external original materials.
Study overlap and independent replication: Independent replication is unverified.

Public availability, access and reading status by material
Material	Public availability	Access status	Actually read	Notes
Publisher original-paper abstract and bibliographic HTML	Unverified (no external lookup in this review)	Access not attempted	Unread	Limited to the preserved identity/access records and the required material type. External existence/public availability was not newly verified in this review. Only the relevant content, evidence, and bibliography in the currently preserved archived source summary were read. The external material concerned was not read in this review. Only the extent to which the original citation records access to this physical material itself is preserved. Historical access dates for each material are unverified. The archived manuscript review date 2026-09-15 is not the access date of this original material file. Historical access level of this material itself: primary_abstract. Historical location in the reference bibliography: Abstract; J Peripheral Nervous System 2014;19:136-144 Bibliographic access records are not inherited as access to a separate full text or underlying material. This does not mean that external original materials were acquired or full texts read in this review.
Separate original-paper PDF full text (exact URL/actual historical access unverified)	Unverified (no external lookup in this review)	Access not attempted	Unread	Limited to the preserved identity/access records and the required material type. External existence/public availability was not newly verified in this review. Only the relevant content, evidence, and bibliography in the currently preserved archived source summary were read. The external material concerned was not read in this review. Historical access to the included bibliography/abstract and metadata provides reference context. It is not inherited as the actual access level of a separate original text or underlying material. Historical access dates for each material are unverified. The archived manuscript review date 2026-09-15 is not the access date of this original material file. Historical access level of this material itself: Unverified. Historical location in the reference bibliography: Abstract; J Peripheral Nervous System 2014;19:136-144 Bibliographic access records are not inherited as access to a separate full text or underlying material. This does not mean that external original materials were acquired or full texts read in this review.

S24 · Pyridoxine-induced sensory ataxic neuronopathy and neuropathy: revisited

Source

Material type: Original-paper abstract (historical access)
Materials actually read: The relevant Korean/English summaries and bibliographic records in the archived manuscript were read. The linked external original materials were not read in this review.
Findings recorded in the stored summary: Record at the time of preservation: Aged 80·83·83, the 3 people had cases of sensory ataxic neuropathy/gait impairment. They took B1/B6/B12 combination tablets providing pyridoxine 600 mg/day for 3–10 years, with no significant improvement even 2 years after withdrawal. No single-ingredient-product incidence or probability of permanent damage is presented.
Record level: This is content recorded in the archived manuscript. It is not the result of a new comparison with current external original materials.
Study overlap and independent replication: Independent replication is unverified.

Public availability, access and reading status by material
Material	Public availability	Access status	Actually read	Notes
PubMed original-paper abstract and bibliographic record	Unverified (no external lookup in this review)	Access not attempted	Unread	Limited to the preserved identity/access records and the required material type. External existence/public availability was not newly verified in this review. Only the relevant content, evidence, and bibliography in the currently preserved archived source summary were read. The external material concerned was not read in this review. Only the extent to which the original citation records access to this physical material itself is preserved. Historical access dates for each material are unverified. The archived manuscript review date 2026-09-15 is not the access date of this original material file. Historical access level of this material itself: primary_abstract. Historical location in the reference bibliography: Abstract; Neurol Sci 2014;35(11):1827-1830 Bibliographic access records are not inherited as access to a separate full text or underlying material. This does not mean that external original materials were acquired or full texts read in this review.
Separate original-paper PDF full text (exact URL/actual historical access unverified)	Unverified (no external lookup in this review)	Access not attempted	Unread	Limited to the preserved identity/access records and the required material type. External existence/public availability was not newly verified in this review. Only the relevant content, evidence, and bibliography in the currently preserved archived source summary were read. The external material concerned was not read in this review. Historical access to the included bibliography/abstract and metadata provides reference context. It is not inherited as the actual access level of a separate original text or underlying material. Historical access dates for each material are unverified. The archived manuscript review date 2026-09-15 is not the access date of this original material file. Historical access level of this material itself: Unverified. Historical location in the reference bibliography: Abstract; Neurol Sci 2014;35(11):1827-1830 Bibliographic access records are not inherited as access to a separate full text or underlying material. This does not mean that external original materials were acquired or full texts read in this review.

S25 · Neuropsychiatric toxicity and cycloserine concentrations during treatment for multidrug-resistant tuberculosis

Source

Material type: Original-paper abstract, declarations/support indexing (historical access)
Materials actually read: The relevant Korean/English summaries and bibliographic records in the archived manuscript were read. The linked external original materials were not read in this review.
Findings recorded in the stored summary: Record at the time of preservation: Recruitment was 144 people, with neuropathy in 50 (35% in the original). For pyridoxine 200 versus 150 mg/day, an adjusted HR of 2.79, P=0.01, was reported for mixed new/worsened events. Arm-specific denominators/events, CI, exact follow-up, and separate counts are unverified, and HIV/TB, concomitant treatment, and prescribing confounding remain. The composite neuropsychiatric AE person-month incidence is not repurposed. NIH/NIAID·Wellcome grants are limited to the indexing record.
Record level: This is content recorded in the archived manuscript. It is not the result of a new comparison with current external original materials.
Study overlap and independent replication: Independent replication is unverified.

Public availability, access and reading status by material
Material	Public availability	Access status	Actually read	Notes
PubMed abstract, figure captions, and COI/Grants indexing	Unverified (no external lookup in this review)	Access not attempted	Unread	Limited to the preserved identity/access records and the required material type. External existence/public availability was not newly verified in this review. Only the relevant content, evidence, and bibliography in the currently preserved archived source summary were read. The external material concerned was not read in this review. Only the extent to which the original citation records access to this physical material itself is preserved. Historical access dates for each material are unverified. The archived manuscript review date 2026-09-15 is not the access date of this original material file. Historical access level of this material itself: primary_abstract_declarations_funding. Historical location in the reference bibliography: Abstract Methods/Results/Conclusions; figure captions; COI; Grants and funding; IJID 2021;105:688-694 Bibliographic access records are not inherited as access to a separate full text or underlying material. This does not mean that external original materials were acquired or full texts read in this review.
Separate original-paper PDF full text (exact URL/actual historical access unverified)	Unverified (no external lookup in this review)	Access not attempted	Unread	Limited to the preserved identity/access records and the required material type. External existence/public availability was not newly verified in this review. Only the relevant content, evidence, and bibliography in the currently preserved archived source summary were read. The external material concerned was not read in this review. Historical access to the included bibliography/abstract and metadata provides reference context. It is not inherited as the actual access level of a separate original text or underlying material. Historical access dates for each material are unverified. The archived manuscript review date 2026-09-15 is not the access date of this original material file. Historical access level of this material itself: Unverified. Historical location in the reference bibliography: Abstract Methods/Results/Conclusions; figure captions; COI; Grants and funding; IJID 2021;105:688-694 Bibliographic access records are not inherited as access to a separate full text or underlying material. This does not mean that external original materials were acquired or full texts read in this review.

S26 · Regressive pyridoxine-induced sensory neuronopathy in a patient with homocystinuria

Source

Material type: Candidate original-paper metadata/search snippet (historical; original results not acquired)
Materials actually read: The relevant Korean/English summaries and bibliographic records in the archived manuscript were read. The linked external original materials were not read in this review.
Findings recorded in the stored summary: Record at the time of preservation: The title/DOI/PMID of a recovery case were identified. An empty original PubMed body, PMC6040505 captcha, and BMJ fetch failure are recorded in the historical location; the complete abstract/full text was not acquired, so it was not used for quantitative values/a recovery guarantee. This is not upgraded to a failure in this review or evidence of clinical absence in unread material.
Record level: This is content recorded in the archived manuscript. It is not the result of a new comparison with current external original materials.
Study overlap and independent replication: Independent replication is unverified.

Public availability, access and reading status by material
Material	Public availability	Access status	Actually read	Notes
PubMed bibliographic/candidate metadata route	Unverified (no external lookup in this review)	Access not attempted	Unread	Limited to the preserved identity/access records and the required material type. External existence/public availability was not newly verified in this review. Only the relevant content, evidence, and bibliography in the currently preserved archived source summary were read. The external material concerned was not read in this review. Only the extent to which the original citation records access to this physical material itself is preserved. Historical access dates for each material are unverified. The archived manuscript review date 2026-09-15 is not the access date of this original material file. Historical access level of this material itself: metadata_search_snippet_primary_text_unavailable. Historical location in the reference bibliography: Search metadata; PubMed empty body; PMC6040505 captcha; BMJ fetch failure Bibliographic access records are not inherited as access to a separate full text or underlying material. This does not mean that external original materials were acquired or full texts read in this review.
Separate BMJ/PMC original-paper full text (exact URL/actual historical access unverified)	Unverified (no external lookup in this review)	Access not attempted	Unread	Limited to the preserved identity/access records and the required material type. External existence/public availability was not newly verified in this review. Only the relevant content, evidence, and bibliography in the currently preserved archived source summary were read. The external material concerned was not read in this review. Historical access to the included bibliography/abstract and metadata provides reference context. It is not inherited as the actual access level of a separate original text or underlying material. Historical access dates for each material are unverified. The archived manuscript review date 2026-09-15 is not the access date of this original material file. Historical access level of this material itself: Unverified. Historical location in the reference bibliography: Search metadata; PubMed empty body; PMC6040505 captcha; BMJ fetch failure Bibliographic access records are not inherited as access to a separate full text or underlying material. This does not mean that external original materials were acquired or full texts read in this review.

S27 · No sensory neuropathy during pyridoxine treatment in homocystinuria

Source

Material type: PMC candidate original-paper link (historically only metadata verified/original text not acquired)
Materials actually read: The relevant Korean/English summaries and bibliographic records in the archived manuscript were read. The linked external original materials were not read in this review.
Findings recorded in the stored summary: Record at the time of preservation: The title No sensory neuropathy during pyridoxine treatment in homocystinuria and its DOI were identified. Because of a PMC captcha/publisher fetch failure, values from the original full text/complete abstract were not used. The title is not interpreted as 0 adverse events, long-term safety, or absence of risk.
Record level: This is content recorded in the archived manuscript. It is not the result of a new comparison with current external original materials.
Study overlap and independent replication: Independent replication is unverified.

Public availability, access and reading status by material
Material	Public availability	Access status	Actually read	Notes
PMC original-paper HTML link (historically only metadata verified)	Unverified (no external lookup in this review)	Access not attempted	Unread	Limited to the preserved identity/access records and the required material type. External existence/public availability was not newly verified in this review. Only the relevant content, evidence, and bibliography in the currently preserved archived source summary were read. The external material concerned was not read in this review. Historical access to the included bibliography/abstract and metadata provides reference context. It is not inherited as the actual access level of a separate original text or underlying material. Historical access dates for each material are unverified. The archived manuscript review date 2026-09-15 is not the access date of this original material file. Historical access level of this material itself: Unverified. Historical location in the reference bibliography: Article metadata identified; PMC captcha; publisher fetch failed Bibliographic access records are not inherited as access to a separate full text or underlying material. This does not mean that external original materials were acquired or full texts read in this review.

S28 · Sensory neuropathy from pyridoxine abuse. A new megavitamin syndrome

Source

Material type: Candidate original-paper metadata (historical; original text not acquired)
Materials actually read: The relevant Korean/English summaries and bibliographic records in the archived manuscript were read. The linked external original materials were not read in this review.
Findings recorded in the stored summary: Record at the time of preservation: The title Sensory neuropathy from pyridoxine abuse and DOI/PMID were identified. The EFSA reference and PubMed empty response/NEJM access failure are recorded in the historical location. The current source lacks details of original denominators/exact exposure, duration, and events, so these were not used as new values.
Record level: This is content recorded in the archived manuscript. It is not the result of a new comparison with current external original materials.
Study overlap and independent replication: Independent replication is unverified.

Public availability, access and reading status by material
Material	Public availability	Access status	Actually read	Notes
PubMed candidate bibliographic route	Unverified (no external lookup in this review)	Access not attempted	Unread	Limited to the preserved identity/access records and the required material type. External existence/public availability was not newly verified in this review. Only the relevant content, evidence, and bibliography in the currently preserved archived source summary were read. The external material concerned was not read in this review. Only the extent to which the original citation records access to this physical material itself is preserved. Historical access dates for each material are unverified. The archived manuscript review date 2026-09-15 is not the access date of this original material file. Historical access level of this material itself: metadata_primary_text_unavailable. Historical location in the reference bibliography: Reference in EFSA; PubMed empty response; NEJM access failed Bibliographic access records are not inherited as access to a separate full text or underlying material. This does not mean that external original materials were acquired or full texts read in this review.
Separate NEJM original-paper PDF full text (exact URL/actual historical access unverified)	Unverified (no external lookup in this review)	Access not attempted	Unread	Limited to the preserved identity/access records and the required material type. External existence/public availability was not newly verified in this review. Only the relevant content, evidence, and bibliography in the currently preserved archived source summary were read. The external material concerned was not read in this review. Historical access to the included bibliography/abstract and metadata provides reference context. It is not inherited as the actual access level of a separate original text or underlying material. Historical access dates for each material are unverified. The archived manuscript review date 2026-09-15 is not the access date of this original material file. Historical access level of this material itself: Unverified. Historical location in the reference bibliography: Reference in EFSA; PubMed empty response; NEJM access failed Bibliographic access records are not inherited as access to a separate full text or underlying material. This does not mean that external original materials were acquired or full texts read in this review.

Report counts versus independent study counts

The 6 archived evidence families do not represent the number of independent clinical trials or a participant total. F-BERGER (S20, S14): Evidence for high-dose pyridoxine causality; not used as population incidence / F-LAREB (S21, S22, S14): Used as a safety signal; counts are not summed as mutually independent / F-TGA (S11, S12): Evidence for a possible low-dose signal and label warnings; not a biological threshold / F-VISSER (S23): Contrary/limiting evidence preserved; neither a no-risk guarantee nor a causal incidence estimate / F-KULKANTRAKORN (S24): Warning of possible persistent harm; probability of permanent damage cannot be calculated / F-COURT (S25): Contextual evidence from a dose comparison; not repurposed as a causal RR for general supplement use. Duplicate counts of the same reports and repeat citations in official documents are not summed.

Review criteria

Version NGM-v3098-ORAL-B6-CLINICAL-SENSORY-NEUROPATHY-HARM-1.1 · Criteria record date 2026-10-05. These are Chamgap's own application conditions, informed by the referenced methods. They do not constitute official assessment-tool certification or a new efficacy score.

N01 · Were the original safety-only designation and the contract that efficacy is not applicable preserved?

Required materials and conditions: Original safety designation, assessment contract, and document-quality metadata
Conditions for verification: Preserve the links between safety_only true, efficacy not_applicable, framework false, and the original values/absences, without assigning an efficacy badge or total score.
Requirement and applicability: Required
Application exceptions: The original grade ?, empty score value, document quality B, and empty axis_notes are not converted into new efficacy/risk scores.
Why this condition is needed: Required to avoid mixing the original warning for the harm question with the meanings of efficacy/document quality.
Referenced methods: C01: Question-clarification principles in M03 §3.1, §3.2.1–3.2.4; detailed separation rules are internally designed / C09: M04 §4.5, §4.6.3; limitations on the current material conversion reflect the user-defined scope and internal design / H09: Chamgap's own interpretation boundaries. M19 principles are referenced; no formal causality tool was applied / E10: M19 §19.1.2–19.2.4; internal application. Rationale for application to this case: required to avoid mixing the original warning for the harm question with the meanings of efficacy/document quality. No formal causality/harm grading assessment was performed.

N02 · Was the separate question of oral B6 and new or worsened clinical sensory neuropathy fixed?

Required materials and conditions: Original claim, population/exposure, route, and endpoint boundaries
Conditions for verification: Link the original claim to oral supplement/medicine exposure and clinical new-onset/worsening endpoints, and specify the exclusions.
Requirement and applicability: Required
Application exceptions: The scope is not extended to food/parenteral exposure, animals, changes in test values alone, or all neuropathy from other causes.
Why this condition is needed: Required to distinguish the harm claim from questions about efficacy for treating pre-existing neuropathy or changes in test results.
Referenced methods: C01: Question-clarification principles in M03 §3.1, §3.2.1–3.2.4; detailed separation rules are internally designed / C05: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptation to testing are internally designed / H01: M19 §19.1.2–19.2.4; detailed distinctions are internally designed / H09: Chamgap's own interpretation boundaries. M19 principles are referenced; no formal causality tool was applied. Rationale for application to this case: required to distinguish the harm claim from questions about efficacy for treating pre-existing neuropathy or changes in test results. No formal causality/harm grading assessment was performed.

N03 · Are the B6 vitamer, salt, and formulation identities established for each source?

Required materials and conditions: Original formulation composition, vitamer/salt, and product description
Conditions for verification: Verify the substance and salt actually reported in each source, and leave detailed identity unverified where it is unavailable.
Requirement and applicability: Required
Application exceptions: Material reporting only pyridoxine is not filled in as the hydrochloride, and absence of risk for PLP is not inferred.
Why this condition is needed: Required to avoid combining different exposures, such as pyridoxine, its hydrochloride, and PLP/P5P, as having the same toxic potency.
Referenced methods: C05: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptation to testing are internally designed / H05: Design considerations in M19 §19.2.2–19.2.4; detailed recording of confounding is internally designed. Rationale for application to this case: required to avoid combining different exposures, such as pyridoxine, its hydrochloride, and PLP/P5P, as having the same toxic potency. No formal causality/harm grading assessment was performed.

N04 · Are the brand, batch, measured content, and actual dose taken verified?

Required materials and conditions: Manufacturing/labeling, batch, measured content, and dosing frequency/adherence records
Conditions for verification: Verify the exact product, ingredients/release, measured content, and actual dosing frequency/adherence, and identify the remaining gaps.
Requirement and applicability: Required
Application exceptions: The labeled tablet/capsule amount is not treated as verification of purity, batch/release, dosing frequency, or adherence.
Why this condition is needed: Required to avoid generalizing a nominal administered dose into actual intake or risk for the entire product.
Referenced methods: C05: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptation to testing are internally designed / E02: M03 §3.2.3, M08 §8.2.2–8.2.3; internal application / H05: Design considerations in M19 §19.2.2–19.2.4; detailed recording of confounding is internally designed. Rationale for application to this case: required to avoid generalizing a nominal administered dose into actual intake or risk for the entire product. No formal causality/harm grading assessment was performed.

N05 · Can content per tablet be distinguished from actual total daily intake across multiple products?

Required materials and conditions: Product-specific content units, dosing frequency/number taken, and concurrent-exposure table
Conditions for verification: Link content units, number of products, dosing frequency, and background intake, without calculating totals that have not been verified.
Requirement and applicability: Required
Application exceptions: 1.4–100 mg is a per-tablet amount, and the TGA's 9 reports involving multiple products are not an independent group with verified total daily intake.
Why this condition is needed: Required to avoid converting Lareb's per-tablet content or reports involving multiple products into a daily dose/risk threshold.
Referenced methods: C05: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptation to testing are internally designed / E02: M03 §3.2.3, M08 §8.2.2–8.2.3; internal application / H04: M19 §19.1.2–19.2.4; internal application / H05: Design considerations in M19 §19.2.2–19.2.4; detailed recording of confounding is internally designed. Rationale for application to this case: required to avoid converting Lareb's per-tablet content or reports involving multiple products into a daily dose/risk threshold. No formal causality/harm grading assessment was performed.

N06 · Was oral exposure from supplements/medicines separated from other routes/foods?

Required materials and conditions: Original route, exposure source, and applicability of related material
Conditions for verification: Preserve the original exposure strata for oral supplements/medicines and prevent direct extrapolation from other routes.
Requirement and applicability: Required
Application exceptions: Ordinary/fortified foods, parenteral dosing, and animal dosing are not evidence of identical risk for exposure to these formulations.
Why this condition is needed: Required to avoid transferring human incidence after oral exposure across routes and exposure sources.
Referenced methods: C01: Question-clarification principles in M03 §3.1, §3.2.1–3.2.4; detailed separation rules are internally designed / C05: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptation to testing are internally designed / H09: Chamgap's own interpretation boundaries. M19 principles are referenced; no formal causality tool was applied. Rationale for application to this case: required to avoid transferring human incidence after oral exposure across routes and exposure sources. No formal causality/harm grading assessment was performed.

N07 · Are the population, pre-exposure neuropathy, and underlying diseases verified for each source?

Required materials and conditions: Table of inclusion/exclusion, baseline symptoms, examination/disease, renal/hepatic status, and medications
Conditions for verification: Link the study-specific population, baseline neuropathy, renal/hepatic status, medications, and selection status, and explicitly identify omissions.
Requirement and applicability: Required
Application exceptions: The category of predominantly adults is not converted into normal individual baseline status or safety for special populations.
Why this condition is needed: Required to avoid combining healthy volunteers, people with existing CIAP, TB/HIV, and older adults into the same population for new-onset events.
Referenced methods: C04: M03 §3.2.1; detailed population conditions are internally designed / H05: Design considerations in M19 §19.2.2–19.2.4; detailed recording of confounding is internally designed / H08: M19 §19.1.2–19.2.4; internal application. Rationale for application to this case: required to avoid combining healthy volunteers, people with existing CIAP, TB/HIV, and older adults into the same population for new-onset events. No formal causality/harm grading assessment was performed.

N08 · Was clinical sensory neuropathy confirmed/ascertained separately from test markers?

Required materials and conditions: Original diagnostic criteria, symptoms/examination, QST/conduction, and detection/blinding procedures
Conditions for verification: Verify symptoms, signs/examination, and confirmation/ascertainment procedures, and separate changes in markers alone from clinical events.
Requirement and applicability: Required
Application exceptions: Participants with changes in test results alone and no clinical symptoms are not included as clinical events.
Why this condition is needed: Required to avoid substituting changes in PLP/QST/conduction or high blood B6 values for clinical occurrence.
Referenced methods: C06: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed / E03: M08 Table 8.2.a, M03 §3.2.4; internal application / E09: M03 §3.2.4; internally defined extension boundaries / H01: M19 §19.1.2–19.2.4; detailed distinctions are internally designed. Rationale for application to this case: required to avoid substituting changes in PLP/QST/conduction or high blood B6 values for clinical occurrence. No formal causality/harm grading assessment was performed.

N09 · Can new onset and worsening of pre-existing symptoms be distinguished separately?

Required materials and conditions: Table of baseline symptoms, event counts for new onset/worsening, populations at risk, and timing
Conditions for verification: Verify pre-exposure symptoms and events, denominators, and timing for new onset/worsening, and leave mixed outcomes as mixed.
Requirement and applicability: Required
Application exceptions: The mixture of new onset/worsening in the TB cohort or incomplete classification in spontaneous reports is not filled in as separately available values.
Why this condition is needed: Required to avoid converting results for a mixed endpoint into a single incidence rate of new toxicity.
Referenced methods: C06: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed / H01: M19 §19.1.2–19.2.4; detailed distinctions are internally designed / H04: M19 §19.1.2–19.2.4; internal application. Rationale for application to this case: required to avoid converting results for a mixed endpoint into a single incidence rate of new toxicity. No formal causality/harm grading assessment was performed.

N10 · Were Berger's reported doses separated from observations of onset and after withdrawal?

Required materials and conditions: Original table of dosing/onset and follow-up after withdrawal
Conditions for verification: Attribute the 5 volunteers, reported pyridoxine doses of 1 or 3 g/day, earlier onset, and worsening for 2–3 weeks after withdrawal to their original locations.
Requirement and applicability: Required
Application exceptions: 1 or 3 g/day is not converted into a general recommended dose, minimum risk dose, or individual actual cumulative exposure.
Why this condition is needed: Required to avoid extending temporal relationships at high doses to low doses generally/all users.
Referenced methods: C05: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptation to testing are internally designed / C06: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed / H02: Design-specific harm questions in M19 §19.2; temporal-relationship details are internally designed. Rationale for application to this case: required to avoid extending temporal relationships at high doses to low doses generally/all users. No formal causality/harm grading assessment was performed.

N11 · Is Berger's actual number of clinical cases consistently verified across sources?

Required materials and conditions: Correspondence between the original abstract, individual clinical symptom/test table, and EFSA extraction
Conditions for verification: Compare symptom/test criteria and clinical numerators in the original abstract and EFSA's individual-participant extraction. If disagreement remains, do not treat the numerator as established or claim 100% occurrence.
Requirement and applicability: Required
Application exceptions: Distinguish successful recording of the conflict as it stands from a status in which the clinical numerator has been consistently verified.
Why this condition is needed: Required to avoid automatically interpreting the denominator of 5 volunteers as 5/5 clinical occurrence.
Referenced methods: C07: M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptations are internally designed / C08: M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses is internally designed / H01: M19 §19.1.2–19.2.4; detailed distinctions are internally designed / H04: M19 §19.1.2–19.2.4; internal application. Rationale for application to this case: required to avoid automatically interpreting the denominator of 5 volunteers as 5/5 clinical occurrence. No formal causality/harm grading assessment was performed.

N12 · Were the uncontrolled design of the high-dose experiment and the boundaries of comparative risk preserved?

Required materials and conditions: Original design, comparator/allocation, and exposure table
Conditions for verification: Explicitly identify the uncontrolled prospective high-dose design and distinguish it from estimation of population incidence/RR.
Requirement and applicability: Required
Application exceptions: Observations at the alternative doses 1 or 3 g are not treated as an RCT effect with an unexposed control.
Why this condition is needed: Required to avoid converting the temporal relationship of prospective exposure into a randomized comparison with no exposure or a population risk rate.
Referenced methods: C05: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptation to testing are internally designed / E01: M08 §8.1–8.2.3; internal application / H03: M19 §19.2.2–19.2.4, M03 §3.2.3; internal application. Rationale for application to this case: required to avoid converting the temporal relationship of prospective exposure into a randomized comparison with no exposure or a population risk rate. No formal causality/harm grading assessment was performed.

N13 · Are recovery/worsening after withdrawal and the actual course on rechallenge verified?

Required materials and conditions: Original individual event records for withdrawal, follow-up/function, and rechallenge
Conditions for verification: Verify withdrawal/course, completeness of recovery, and rechallenge for each individual, and retain the areas with insufficient information.
Requirement and applicability: Required
Application exceptions: Coasting, persistent disability, and cases of recovery after withdrawal are not converted into a guarantee of individual recovery or a probability of permanent damage.
Why this condition is needed: Required to avoid extending some improvement into complete recovery for everyone or confirmation through rechallenge.
Referenced methods: H02: Design-specific harm questions in M19 §19.2; temporal-relationship details are internally designed / H08: M19 §19.1.2–19.2.4; internal application / H09: Chamgap's own interpretation boundaries. M19 principles are referenced; no formal causality tool was applied. Rationale for application to this case: required to avoid extending some improvement into complete recovery for everyone or confirmation through rechallenge. No formal causality/harm grading assessment was performed.

N14 · Are the independence and overlap relationships of Lareb reports verified?

Required materials and conditions: Original report identifiers, collection period, and overlap/re-citation correspondence table
Conditions for verification: Link the series, collection period, and overlap relationships, and do not sum counts when individual overlap/independent events are unverified.
Requirement and applicability: Required
Application exceptions: 90 and 224 overlap within the same reporting series, and official re-citations are not separate replications in humans.
Why this condition is needed: Required to avoid adding the 2018/2025/EFSA interim counts as independent reports/trials.
Referenced methods: C02: Distinction between studies and reports in M04 §4.6.1–4.6.2; cohort/outcome linkage is an internal application / E07: M04 §4.6.1–4.6.2, M15 §15.3.1; internal application / H07: M04 §4.6.1–4.6.2; adaptation to harm material is internally designed. Rationale for application to this case: required to avoid adding the 2018/2025/EFSA interim counts as independent reports/trials. No formal causality/harm grading assessment was performed.

N15 · Were the Lareb collection period and the historical reference dates of the material separated?

Required materials and conditions: Original analysis collection window and publication/review metadata
Conditions for verification: Preserve the 2025 analysis's report collection window, 2007-08–2023-12-31, separately from publication/review dates.
Requirement and applicability: Required
Application exceptions: The report collection end on 2023-12-31, the 2025 analysis, the original review on 2026-09-15, and the date of this review are different events.
Why this condition is needed: Required to avoid changing the end date of report collection into the publication/review date or the date of this lookup.
Referenced methods: C06: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed / C09: M04 §4.5, §4.6.3; limitations on the current material conversion reflect the user-defined scope and internal design / H02: Design-specific harm questions in M19 §19.2; temporal-relationship details are internally designed. Rationale for application to this case: required to avoid changing the end date of report collection into the publication/review date or the date of this lookup. No formal causality/harm grading assessment was performed.

N16 · Are clinical confirmation, actual exposure duration, and completeness of collection of Lareb reports verified?

Required materials and conditions: Original report table of diagnosis/exposure/duration, detection/selection, and follow-up
Conditions for verification: Check the clinical definition/confirmation, exposure/onset periods, alternative causes, and missed detection for each report.
Requirement and applicability: Required
Application exceptions: Blood B6 values or titles are not used to substitute for gaps in report selection, diagnosis, or exposure.
Why this condition is needed: Required to avoid treating reported neuropathy as consistently confirmed new-onset events.
Referenced methods: C06: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptation is internally designed / H01: M19 §19.1.2–19.2.4; detailed distinctions are internally designed / H02: M19 §19.2 design-specific harm questions; details of temporal relationships are internally designed / H06: M19 §19.1.2–19.2.4, M04 §4.6.3; internal application. Rationale for application to this case: needed to avoid treating reported neuropathy as consistently confirmed new clinical events. No formal causality/harm grading assessment was performed.

N17 · Is a denominator verified for calculating incidence among exposed persons from spontaneous reports?

Required materials and conditions: Data on all exposed persons, observation time by dose, all/confirmed events, and unreported cases
Conditions for verification: Do not present incidence unless all exposed persons, observation time, and event counts for the same event/dose/duration have been verified.
Requirement and applicability: Required
Application exceptions: Report counts, counts of blood tests, and content per tablet are not exposed-person counts or person-time.
Why this condition is needed: Needed to avoid converting report counts into probabilities of occurrence among all users or dose groups.
Referenced methods: C07: M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptation is internally designed / H04: M19 §19.1.2–19.2.4; internal application / H09: Chamgap’s own interpretive boundaries. M19 principles are referenced; no formal causality tool was applied. Rationale for application to this case: needed to avoid converting report counts into probabilities of occurrence among all users or dose groups. No formal causality/harm grading assessment was performed.

N18 · Can selection and overlap in TGA’s 32 reports and low-dose/multiple-product categories be verified?

Required materials and conditions: Original TGA tables of report selection, clinical confirmation, and overlap between dose/multiple-product categories
Conditions for verification: Verify the selection criteria, categories/overlap, and actual denominator meanings of 32·21·9, while retaining unverified selection processes as unverified.
Requirement and applicability: Required
Application exceptions: The 21 reports and 9 reports may overlap; the 32 reports are not substituted for all reports/exposed persons or fully confirmed events.
Why this condition is needed: Needed to avoid mistaking the composition of selected reports for comparative risk among all users by dose.
Referenced methods: C04: M03 §3.2.1; detailed population conditions are internally designed / C07: M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptation is internally designed / H04: M19 §19.1.2–19.2.4; internal application / H06: M19 §19.1.2–19.2.4, M04 §4.6.3; internal application. Rationale for application to this case: needed to avoid mistaking the composition of selected reports for comparative risk among all users by dose. No formal causality/harm grading assessment was performed.

N19 · Are comparative risk, causality, and a no-risk boundary at low doses established?

Required materials and conditions: Exposure/comparator, event, duration, confounding, and risk-estimate data for each low dose
Conditions for verification: Retain the scope of dose-specific risk verification based on actual comparators/denominators, precise exposure, other causes/duration, and clinical events.
Requirement and applicability: Required
Application exceptions: The composition of reports involving ≤50 mg/day and the labeling warning for >10 mg are not the same biological threshold.
Why this condition is needed: Needed to avoid converting a possible signal from low-dose reports into confirmed causality at all low doses or safety at all low doses.
Referenced methods: H03: M19 §19.2.2–19.2.4, M03 §3.2.3; internal application / H04: M19 §19.1.2–19.2.4; internal application / H09: Chamgap’s own interpretive boundaries. M19 principles are referenced; no formal causality tool was applied. Rationale for application to this case: needed to avoid converting a possible signal from low-dose reports into confirmed causality at all low doses or safety at all low doses. No formal causality/harm grading assessment was performed.

N20 · Are the dose-specific comparative estimate and its uncertainty in the tuberculosis cohort verified?

Required materials and conditions: Tables of exposure/events, denominators, adjustment models, HR/CI, and follow-up by dose group
Conditions for verification: Distinguish the 200 versus 150 mg/day comparison and adjusted HR/P from the actual scope of verification of group-specific denominators/events, CI, and follow-up.
Requirement and applicability: Required
Application exceptions: The 144 people and 50 people (35% in the original) and HR 2.79 do not substitute for group-specific denominators/event counts or CI.
Why this condition is needed: Needed to avoid transferring the reported HR to a causal RR for general supplement use or an exact incidence rate.
Referenced methods: C05: M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptation are internally designed / C07: M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptation is internally designed / E04: M08 §8.2.2, M15 §15.3.1; internal application / E05: M15 §15.3.1–15.3.3; internal application / H03: M19 §19.2.2–19.2.4, M03 §3.2.3; internal application / H04: M19 §19.1.2–19.2.4; internal application. Rationale for application to this case: needed to avoid transferring the reported HR to a causal RR for general supplement use or an exact incidence rate. No formal causality/harm grading assessment was performed.

N21 · Were the nonrandomized doses in the tuberculosis cohort and limitations on application to general supplement use preserved?

Required materials and conditions: Original recruitment/prescribing, population/concurrent treatment, and actual comparator design
Conditions for verification: Indicate the original design, population/co-medication, and nonrandomized doses, and prevent transfer of the HR to an RR for general users.
Requirement and applicability: Required
Application exceptions: Do not equate the TB/HIV and terizidone/cycloserine context with general exposure to a single-ingredient supplement.
Why this condition is needed: Needed to avoid converting a nonrandomized comparison in a treatment setting into an RCT causal effect among healthy users.
Referenced methods: C04: M03 §3.2.1; detailed population conditions are internally designed / E01: M08 §8.1–8.2.3; internal application / H03: M19 §19.2.2–19.2.4, M03 §3.2.3; internal application / H05: M19 §19.2.2–19.2.4 design considerations; detailed confounding records are internally designed. Rationale for application to this case: needed to avoid converting a nonrandomized comparison in a treatment setting into an RCT causal effect among healthy users. No formal causality/harm grading assessment was performed.

N22 · Was confounding by tuberculosis/HIV, medications, and prescribing reasons sufficiently controlled?

Required materials and conditions: Original adjustment-model, prescribing/underlying-disease, medication, and exposure-follow-up data
Conditions for verification: Check model variables, prescribing reasons, baseline status/concurrent medications, exposure deviations, and residual confounding.
Requirement and applicability: Required
Application exceptions: The term adjusted HR alone does not eliminate residual confounding from prescribing indications, baseline neuropathy, or disease/co-medication.
Why this condition is needed: Needed to avoid establishing the association with B6 dose as a cause independent of medications and diseases.
Referenced methods: H05: M19 §19.2.2–19.2.4 design considerations; detailed confounding records are internally designed / C04: M03 §3.2.1; detailed population conditions are internally designed / E02: M03 §3.2.3, M08 §8.2.2–8.2.3; internal application. Rationale for application to this case: needed to avoid establishing the association with B6 dose as a cause independent of medications and diseases. No formal causality/harm grading assessment was performed.

N23 · Can the endpoint/time denominator for TB neuropathy be separated from other neuropsychiatric AE?

Required materials and conditions: Neuropathy-specific tables of definitions/confirmation, events/time, and missing data/discontinuation
Conditions for verification: Separately verify the definition, new/worsened status, follow-up/denominator, and missing data for neuropathy, and prevent transfer of the composite AE incidence.
Requirement and applicability: Required
Application exceptions: The mixed new/worsened count of 50 people is not a separate count of clinically confirmed new events or an exposure-time denominator.
Why this condition is needed: Needed to avoid transferring the person-month incidence of all neuropsychiatric AE to sensory neuropathy.
Referenced methods: C06: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptation is internally designed / H01: M19 §19.1.2–19.2.4; detailed distinctions are internally designed / H04: M19 §19.1.2–19.2.4; internal application / H06: M19 §19.1.2–19.2.4, M04 §4.6.3; internal application. Rationale for application to this case: needed to avoid transferring the person-month incidence of all neuropsychiatric AE to sensory neuropathy. No formal causality/harm grading assessment was performed.

N24 · Was pre-existing disease in the CIAP case-control study distinguished from the question of new toxicity?

Required materials and conditions: Original population/design, baseline symptoms, and exposure timing/endpoints
Conditions for verification: Indicate the context of the pre-existing CIAP case-control study and its role, which does not establish incident toxicity or guarantee absence of risk.
Requirement and applicability: Required
Application exceptions: The 381 cases and 140 controls are not a population-at-risk denominator for a cohort with new exposure.
Why this condition is needed: Needed to avoid converting the association between prevalent CIAP and supplement use into risk of new onset.
Referenced methods: C04: M03 §3.2.1; detailed population conditions are internally designed / C06: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptation is internally designed / H03: M19 §19.2.2–19.2.4, M03 §3.2.3; internal application / H09: Chamgap’s own interpretive boundaries. M19 principles are referenced; no formal causality tool was applied. Rationale for application to this case: needed to avoid converting the association between prevalent CIAP and supplement use into risk of new onset. No formal causality/harm grading assessment was performed.

N25 · Were the nonsignificant blood-value result and the supplement-use association in CIAP both preserved?

Required materials and conditions: Original results tables, blood-value/supplement-use estimates, and authors’ interpretation
Conditions for verification: Link the 381/140 participants’ 99/109 nmol/L values and P, the 31%/22% and OR/CI/P, and the authors’ limiting interpretation together according to their original locations.
Requirement and applicability: Required
Application exceptions: Do not convert the blood-value P = 0.58 into a risk of 0, or the supplement-use OR into a causal RR for new toxicity.
Why this condition is needed: Needed to avoid omitting favorable/nonsignificant or contrary results and attributing all neuropathy to B6.
Referenced methods: C08: M04 §4.6.3, M15 §15.3.1–15.3.3; status separation is internally designed / H09: Chamgap’s own interpretive boundaries. M19 principles are referenced; no formal causality tool was applied. Rationale for application to this case: needed to avoid omitting favorable/nonsignificant or contrary results and attributing all neuropathy to B6. No formal causality/harm grading assessment was performed.

N26 · Are reverse causation and alternative causes in CIAP and reports sufficiently verified?

Required materials and conditions: Baseline symptoms, start/sequence of use, examinations/other tests, and alternative diseases/medications
Conditions for verification: Check the temporal order of symptoms/exposure, underlying disease/concurrent medication, selection/measurement, and alternative causes.
Requirement and applicability: Required
Application exceptions: Elevated PLP or supplement use alone does not establish B6 causation or the cause of pre-existing disease.
Why this condition is needed: Needed to review the possibility that B6 was used because of pre-existing symptoms, and neuropathy due to other causes.
Referenced methods: H05: M19 §19.2.2–19.2.4 design considerations; detailed confounding records are internally designed / H06: M19 §19.1.2–19.2.4, M04 §4.6.3; internal application / C04: M03 §3.2.1; detailed population conditions are internally designed. Rationale for application to this case: needed to review the possibility that B6 was used because of pre-existing symptoms, and neuropathy due to other causes. No formal causality/harm grading assessment was performed.

N27 · Can the combination product and actual long-term exposure in 3 older adults be verified?

Required materials and conditions: Original case-specific product/composition, dose/duration, baseline-status, and adherence data
Conditions for verification: Distinguish combination composition, nominal pyridoxine dose, and duration/population from gaps in actual product, adherence, and concurrent exposure data.
Requirement and applicability: Required
Application exceptions: Ages 80·83·83 years in 3 people and 600 mg/day for 3–10 years do not constitute an exposed-person denominator for a single-ingredient product or an individual recommended dose.
Why this condition is needed: Needed to avoid combining cases involving B1/B6/B12 combination tablets into population incidence for single-ingredient B6 products.
Referenced methods: C05: M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptation are internally designed / H05: M19 §19.2.2–19.2.4 design considerations; detailed confounding records are internally designed / H08: M19 §19.1.2–19.2.4; internal application. Rationale for application to this case: needed to avoid combining cases involving B1/B6/B12 combination tablets into population incidence for single-ingredient B6 products. No formal causality/harm grading assessment was performed.

N28 · Are individual recovery/disability assessments and long-term follow-up in the older-adult cases sufficiently verified?

Required materials and conditions: Original withdrawal/follow-up, neurological/gait assessments, alternative causes, and long-term denominators
Conditions for verification: Compare the scope of verification of original neurological/gait assessments, alternative causes, individual follow-up, and completeness of recovery. A summary stating that there was no significant improvement even 2 years after withdrawal is not treated as verification of a complete long-term assessment or a probability of permanent damage.
Requirement and applicability: Required
Application exceptions: No significant improvement is not equivalent to confirmed complete permanent damage, a quantitative incidence rate, or recovery outcomes under other exposures.
Why this condition is needed: Needed to avoid converting cases with no significant improvement 2 years after withdrawal into a probability of permanent damage or inability to recover in everyone.
Referenced methods: H02: M19 §19.2 design-specific harm questions; details of temporal relationships are internally designed / H04: M19 §19.1.2–19.2.4; internal application / H08: M19 §19.1.2–19.2.4; internal application / H09: Chamgap’s own interpretive boundaries. M19 principles are referenced; no formal causality tool was applied. Rationale for application to this case: needed to avoid converting cases with no significant improvement 2 years after withdrawal into a probability of permanent damage or inability to recover in everyone. No formal causality/harm grading assessment was performed.

N29 · Are the original results of candidates concerning recovery, absence of neuropathy, and high doses verified?

Required materials and conditions: S26/S27/S28 original abstracts/full texts and case/results tables
Conditions for verification: Use only the actually verified scope of original results/populations, doses, durations, and confirmation; leave title/metadata candidates unverified.
Requirement and applicability: Required
Application exceptions: Do not convert S26/S27/S28 historical metadata/access failures into failures during this task, an effect of 0, or complete case tables.
Why this condition is needed: Needed to avoid using titles of inaccessible sources as confirmed positive/negative findings or quantitative contrary evidence.
Referenced methods: C03: M04 §4.5–4.6 data-collection/selection principles; separation of access from reading and the hyperlink contract are internally designed / C08: M04 §4.6.3, M15 §15.3.1–15.3.3; status separation is internally designed / C09: M04 §4.5, §4.6.3; limitations of the current material conversion follow the user’s scope and internal design / H07: M04 §4.6.1–4.6.2; adaptation for harm materials is internally designed. Rationale for application to this case: needed to avoid using titles of inaccessible sources as confirmed positive/negative findings or quantitative contrary evidence. No formal causality/harm grading assessment was performed.

N30 · Can original observations for this harm endpoint be traced in copies of the same Levin paper?

Required materials and conditions: Tables of actual harm events, baseline status/exposure, and denominators/durations in that paper
Conditions for verification: Indicate the same-paper/copy relationship and do not fill in harm events, denominators, or doses/durations that are not currently retained.
Requirement and applicability: Required
Application exceptions: S01/S02 are bibliographic/author copies with the same DOI/PMID, but the 6 evidence entries in source contain no detailed rows for those harm events.
Why this condition is needed: Needed to avoid borrowing values from treatment evidence for pre-existing diabetic neuropathy and figures from the adjacent manuscript for this new harm table.
Referenced methods: C01: M03 §3.1, §3.2.1–3.2.4 question-clarification principles; detailed separation rules are internally designed / C02: M04 §4.6.1–4.6.2 distinction between studies and reports; cohort/outcome linkage is an internal application / C03: M04 §4.5–4.6 data-collection/selection principles; separation of access from reading and the hyperlink contract are internally designed / H09: Chamgap’s own interpretive boundaries. M19 principles are referenced; no formal causality tool was applied. Rationale for application to this case: needed to avoid borrowing values from treatment evidence for pre-existing diabetic neuropathy and figures from the adjacent manuscript for this new harm table. No formal causality/harm grading assessment was performed.

N31 · Were official assessments and re-citations excluded from counts of new independent human trials?

Required materials and conditions: Citation lineage in the original official documents, underlying reports, and native family/linked-source lists
Conditions for verification: Link each official document’s background/regulatory/re-citation role to the native evidence families, without issuing an independent count of human studies or participants.
Requirement and applicability: Required
Application exceptions: The authority of an official document does not substitute for individual events, access to original sources, or risk rates.
Why this condition is needed: Needed to avoid inflating counts of TGA/NIH/EFSA documents and re-citations of existing reports/experiments into independent replications.
Referenced methods: C02: M04 §4.6.1–4.6.2 distinction between studies and reports; cohort/outcome linkage is an internal application / H07: M04 §4.6.1–4.6.2; adaptation for harm materials is internally designed / H09: Chamgap’s own interpretive boundaries. M19 principles are referenced; no formal causality tool was applied. Rationale for application to this case: needed to avoid inflating counts of TGA/NIH/EFSA documents and re-citations of existing reports/experiments into independent replications. No formal causality/harm grading assessment was performed.

N32 · Are comparative risk, CI, and background risk applicable to all users verified?

Required materials and conditions: Actual exposed/unexposed, event/denominator, follow-up, RR/RD/CI, and background-risk data
Conditions for verification: Retain the scope of verification of comparative estimates for the same vitamer/formulation, population, event, comparator, duration, and denominator/CI.
Requirement and applicability: Required
Application exceptions: Do not newly calculate a common RR/RD/NNH from case counts, OR, HR, and nutritional/sales criteria.
Why this condition is needed: Needed to avoid combining high-dose causality, cases/reports, and an HR from a special population into a single overall risk rate.
Referenced methods: C07: M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptation is internally designed / E05: M15 §15.3.1–15.3.3; internal application / H03: M19 §19.2.2–19.2.4, M03 §3.2.3; internal application / H04: M19 §19.1.2–19.2.4; internal application / H09: Chamgap’s own interpretive boundaries. M19 principles are referenced; no formal causality tool was applied. Rationale for application to this case: needed to avoid combining high-dose causality, cases/reports, and an HR from a special population into a single overall risk rate. No formal causality/harm grading assessment was performed.

N33 · Are form-specific long-term risks in vulnerable groups and pre-existing neuropathy verified?

Required materials and conditions: Population-specific formulation, baseline status, exposure, long-term event/follow-up, and treatment-context data
Conditions for verification: Check actual exposure/long-term event data and applicability limitations for kidney/liver function, pregnancy/lactation, children, and pre-existing neuropathy.
Requirement and applicability: Required
Application exceptions: Kidney disease with low B6 markers or deficiency/metabolic disease requiring treatment does not constitute evidence of high-dose safety.
Why this condition is needed: Needed to avoid extending adult high-dose/report signals to individual safety/risk rates in children, pregnancy, or kidney disease.
Referenced methods: C04: M03 §3.2.1; detailed population criteria are internally designed / E08: M03 §3.2.1–3.2.4; details on dose, duration, and effect modification are internally designed / H08: M19 §19.1.2–19.2.4; internal application. Reason for application to this case: Needed to avoid extending adult high-dose evidence/reporting signals to individual safety/risk rates in children, pregnancy, or renal disease. No formal causality/harm grading assessment was performed.

N34 · Are the minimum risk dose/duration, individual no-risk boundary, and cumulative exposure established?

Required materials and conditions: Individual measured amounts/doses, duration/adherence, events, and comparison/denominator data
Conditions for verification: Do not present a threshold/cumulative exposure unless individual actual daily doses, duration/adherence, clinical events, and adequate risk comparisons have been verified.
Requirement and applicability: Required
Application exceptions: The dose–onset relationship at high doses and signals from low-dose reports represent different levels of evidence.
Why this condition is needed: Needed to avoid turning unverified daily dose × duration into a new cumulative exposure or no-risk threshold.
Referenced methods: C05: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptation for tests are internally designed / C06: M03 §3.2.4, M15 §15.3.1–15.3.3; adaptation of outcomes to each question is internally designed / H02: M19 §19.2 on design-specific harm questions; details of temporal relationships are internally designed / H04: M19 §19.1.2–19.2.4; internal application / H09: Chamgap's own interpretation boundaries. M19 principles are referenced; no formal causality tool was applied. Reason for application to this case: Needed to avoid turning unverified daily dose × duration into a new cumulative exposure or no-risk threshold. No formal causality/harm grading assessment was performed.

N35 · Have the jurisdictions/purposes of the FNB/EFSA upper intake levels been distinguished from clinical toxicity thresholds?

Required materials and conditions: Preserved FNB/EFSA editions, populations/risk assessments, and basis for UL derivation
Conditions for verification: State the jurisdictions/methods, populations, and nutritional purposes of the preserved editions, and do not repurpose them as therapeutic doses, clinical thresholds, or no-risk guarantees.
Requirement and applicability: Supporting
Application exceptions: The US 100 mg/day and EFSA 12 mg/day are not clinical comparative values obtained from the same harm study.
Why this condition is needed: Needed to avoid turning a nutritional upper intake level into an individual therapeutic dose recommendation/no-risk guarantee.
Referenced methods: C09: M04 §4.5, §4.6.3; limitations on the current material conversion reflect the user's scope and internal design / H08: M19 §19.1.2–19.2.4; internal application / H09: Chamgap's own interpretation boundaries. M19 principles are referenced; no formal causality tool was applied. Reason for application to this case: Needed to avoid turning a nutritional upper intake level into an individual therapeutic dose recommendation/no-risk guarantee. No formal causality/harm grading assessment was performed.

N36 · Have TGA label warnings been distinguished from biological risk boundaries?

Required materials and conditions: Preserved TGA label warning sections, transition/application dates, and products covered
Conditions for verification: Specify the labeling purpose, jurisdiction, application reference date/transition date, and do not use them as clinical risk thresholds.
Requirement and applicability: Supporting
Application exceptions: >10 mg/day and the 2023-03-01 transition deadline are administrative events under the rules preserved as of 2026-09-15.
Why this condition is needed: Needed to avoid mistaking a labeling criterion for the point at which risk begins/an individual safety boundary.
Referenced methods: C09: M04 §4.5, §4.6.3; limitations on the current material conversion reflect the user's scope and internal design / H09: Chamgap's own interpretation boundaries. M19 principles are referenced; no formal causality tool was applied. Reason for application to this case: Needed to avoid mistaking a labeling criterion for the point at which risk begins/an individual safety boundary. No formal causality/harm grading assessment was performed.

N37 · Has the future TGA sales classification been distinguished from current prescription/labeling rules?

Required materials and conditions: Preserved TGA sections on sales classification/effective dates and products covered
Conditions for verification: At the reference date 2026-09-15, separately state the scheduled 2027-06-01 date, dose ranges, and sales purposes.
Requirement and applicability: Supporting
Application exceptions: Pharmacist control at >50–≤200 mg/day and prescription control at >200 mg/day are neither nutritional ULs nor equivalent risk categories.
Why this condition is needed: Needed to avoid retroactively treating regulations scheduled for 2027 as current rules/clinically safe doses in 2026.
Referenced methods: C09: M04 §4.5, §4.6.3; limitations on the current material conversion reflect the user's scope and internal design / H09: Chamgap's own interpretation boundaries. M19 principles are referenced; no formal causality tool was applied. Reason for application to this case: Needed to avoid retroactively treating regulations scheduled for 2027 as current rules/clinically safe doses in 2026. No formal causality/harm grading assessment was performed.

N38 · Is the actual scope of verification of funding, product supply, and conflicts of interest known for each report?

Required materials and conditions: Original funding/COI, product supply, and design/analysis/reporting role declarations
Conditions for verification: Distinguish each report's actual declarations/indexing from unverified funding, supply/roles, and conflicts of interest.
Requirement and applicability: Required
Application exceptions: The 2018 no-funding statement, unverified 2025 funding, and NIH/Wellcome indexed support are not at the same level of verification.
Why this condition is needed: Needed to avoid filling in indexed grants or unverified information as no funding/no industry involvement/independence.
Referenced methods: C10: Chamgap's own conditions for independence and attribution. The official methodology sections used in this pilot do not endorse all of these detailed items. Reason for application to this case: Needed to avoid filling in indexed grants or unverified information as no funding/no industry involvement/independence. No formal causality/harm grading assessment was performed.

N39 · Is the actual scope of verification of registration, plans, and corrections/retractions sufficiently established?

Required materials and conditions: Registration, protocol/SAP, changes, and correction/retraction search logs/original publication records
Conditions for verification: Verify actual registration/protocols, data collection/SAP, changes, correction/retraction searches, and their scope, and leave unavailable original logs unverified.
Requirement and applicability: Required
Application exceptions: An empty registry_id is not proof of no registration, and the search_record wording is not evidence that the search logs were actually read in this review.
Why this condition is needed: Needed to avoid extending unverified information/the recorded search scope into absence of preregistration, absence of corrections, or integrity of the entire literature.
Referenced methods: C09: M04 §4.5, §4.6.3; limitations on the current material conversion reflect the user's scope and internal design / E06: M08 Table 8.2.a, M04 §4.6.3; internal application / H06: M19 §19.1.2–19.2.4, M04 §4.6.3; internal application. Reason for application to this case: Needed to avoid extending unverified information/the recorded search scope into absence of preregistration, absence of corrections, or integrity of the entire literature. No formal causality/harm grading assessment was performed.

N40 · Have the current summary reading, historical access to originals, and review/access dates been distinguished?

Required materials and conditions: Original bytes of the currently preserved archived summaries, citation access locations/identities, and access-date records
Conditions for verification: Record the actual local summary locations/SHA separately from external access not attempted/materials unread, historical material types/access, and empty per-report access dates.
Requirement and applicability: Required
Application exceptions: Do not reuse citations' historical access_level/location or the global verified_date as current full-text access/individual access dates.
Why this condition is needed: Needed to avoid upgrading the reading of preserved archived summaries to reading original full-text papers in this review.
Referenced methods: C03: M04 §4.5–4.6 principles for material collection/selection; separation of access and reading and the hyperlink contract are internally designed / C09: M04 §4.5, §4.6.3; limitations on the current material conversion reflect the user's scope and internal design. Reason for application to this case: Needed to avoid upgrading the reading of preserved archived summaries to reading original full-text papers in this review. No formal causality/harm grading assessment was performed.

N41 · Has the original safety warning been kept from becoming personal treatment/discontinuation instructions?

Required materials and conditions: Original safety warning and personal application/treatment boundary
Conditions for verification: Preserve the original safety information and assessment limitations, and do not newly assign individual recommended doses or instructions for self-directed dose escalation/prescription discontinuation.
Requirement and applicability: Required
Application exceptions: The blue record statuses in the review table and the original warning are not individual safety guarantees or self-treatment instructions.
Why this condition is needed: Needed to avoid turning harm information into instructions to stop/replace prescriptions or take individual doses.
Referenced methods: C01: M03 §3.1, §3.2.1–3.2.4 principles for clarifying the question; detailed separation rules are internally designed / H09: Chamgap's own interpretation boundaries. M19 principles are referenced; no formal causality tool was applied. Reason for application to this case: Needed to avoid turning harm information into instructions to stop/replace prescriptions or take individual doses. No formal causality/harm grading assessment was performed.

Referenced methods and the sections actually reviewed

M03 · Cochrane Handbook 6.5 (2024), chapter updated 2023-08

Official methodology · §3.1, §3.2.1–3.2.3, MECIR C5/C7/C13

Referenced principle: Clearly document the question, eligibility criteria, and reasons for changes, and distinguish intervention variants.
Extent of review: Historical reuse of methodology materials preserved in 1585: the original-byte/SHA-verified copies of 5 HTML files and the principles. This is not new reading of the full methodology or implementation/certification of an official method.

M04 · Cochrane Handbook 6.5.1 (2025), chapter updated 2025-03

Official methodology · §4.5, §4.6.1–4.6.3, MECIR C42

Referenced principle: Distinguish and link studies and reports, and do not exclude a study solely because outcomes are unreported.
Extent of review: Historical reuse of methodology materials preserved in 1585: the original-byte/SHA-verified copies of 5 HTML files and the principles. This is not new reading of the full methodology or implementation/certification of an official method.

M08 · Cochrane Handbook 6.5 (2024), chapter updated 2019-10

Official methodology · §8.1–8.2.3, Table 8.2.a

Referenced principle: Fix the outcome and effect of interest, and review randomization, deviations, missing data, measurement, and selective reporting.
Extent of review: Historical reuse of methodology materials preserved in 1585: the original-byte/SHA-verified copies of 5 HTML files and the principles. This is not new reading of the full methodology or implementation/certification of an official method.

M15 · Cochrane Handbook 6.5 (2024), chapter updated 2023-08

Official methodology · §15.2.4, §15.3.1–15.3.3

Referenced principle: Distinguish effect estimates, intervals, importance, and applicability. Sample size alone does not determine precision.
Extent of review: Historical reuse of methodology materials preserved in 1585: the original-byte/SHA-verified copies of 5 HTML files and the principles. This is not new reading of the full methodology or implementation/certification of an official method.

M19 · Cochrane Handbook 6.5 (2024), chapter updated 2019-10

Official methodology · §19.1.2, §19.2.1–19.2.4

Referenced principle: Harm questions may require designs, populations, and follow-up different from those for efficacy. Case reports do not establish incidence.
Extent of review: Historical reuse of methodology materials preserved in 1585: the original-byte/SHA-verified copies of 5 HTML files and the principles. This is not new reading of the full methodology or implementation/certification of an official method.

What the statuses mean

Met: The relevant narrow conditions for identity/attribution, original values/boundaries, and reading records are met. This is not a new confirmation of clinical causality, efficacy, absence of risk, or external full texts.
Partly verified: Relevant preserved observations exist, but some aspects of actual exposure/events, denominators, methods/attribution could not be established.
Unverified: Not established within the archived materials and the scope verified at that time. This does not mean 0 risk, absence of research worldwide, or access failure in this review.
Conflicting information: Inconsistent preserved descriptions of the same clinical fact remain. Success in recording and preserving the conflict is distinguished from actual consistent verification.
Not applicable: Limited to material roles excluded by the question's boundaries. It is not a substitute for unverified/unread/no risk.
Not reported: Explicitly unreported within the actual preserved manuscript/historical verification scope. This is not extended to the entirety of full texts unread in this review.
Inaccessible: Limited to actual access failure in this review; the absence of external access attempts in this case is not upgraded to a past failure.
Review incomplete: Limited to the lack of current external comparison. It does not mean that the actually completed review of local archived summaries/individual models is incomplete.

Change history

2026-11-02 · Public page/material version 1.0

The public display and data were prepared from the existing 41 items. No new clinical search, verification-status change, or scoring was performed.

The stored-material review date (2026-10-05) and original evidence cut-off (2026-09-15) were retained unchanged.

Researcher downloads

These materials provide the same evidence, scope and verification status as this page.

View all item details

N01 · Were the original safety-only designation and the contract that efficacy is not applicable preserved?

Current findings: The original question type is safety and safety_only is true. efficacy_grade/score are not_applicable, efficacy_framework_applied is false, grade is ?, and score is an empty value. axis_notes is an empty object, and the axes/no_human keys are absent. Document quality B is not a harm grade.
Verification status: Met
Materials actually read: Summary reading: the specified original locations in the currently archived source summaries were actually read. Access to external material types was not attempted, and they were not read in this review.
Why unverified: The narrow condition for preserving the display was verified. Only the original warning, non-applicability of efficacy, and historical values were retained, with no new risk judgment.
Reason for missing information: Efficacy grades and scores are not applicable.
Required materials and conditions: Original safety designation, assessment contract, and document-quality metadata
Materials to obtain first: Original safety designation, assessment contract, and document-quality metadata
Further research: Compare the display fields with the technical preservation of the original safety/non-efficacy contract.
Remaining uncertainty: Efficacy grades and scores are not applicable. This status concerns a narrow scope of record/material verification and does not newly assess clinical causality, occurrence probability, or individual safety.
Conditions for verification: Preserve the links between safety_only true, efficacy not_applicable, framework false, and the original values/absences, without assigning an efficacy badge or total score.
Why this condition is needed: Required to avoid mixing the original warning for the harm question with the meanings of efficacy/document quality.
Application exceptions: The original grade ?, empty score value, document quality B, and empty axis_notes are not converted into new efficacy/risk scores.
Referenced methods: C01: Question-clarification principles in M03 §3.1, §3.2.1–3.2.4; detailed separation rules are internally designed / C09: M04 §4.5, §4.6.3; limitations on the current material conversion reflect the user-defined scope and internal design / H09: Chamgap's own interpretation boundaries. M19 principles are referenced; no formal causality tool was applied / E10: M19 §19.1.2–19.2.4; internal application. Rationale for application to this case: required to avoid mixing the original warning for the harm question with the meanings of efficacy/document quality. No formal causality/harm grading assessment was performed.

Related sources

N02 · Was the separate question of oral B6 and new or worsened clinical sensory neuropathy fixed?

Current findings: The archived harm question concerns the risk of new or worsened clinical sensory neuropathy. The main exposure is oral B6 from supplements/medicines in adults; ordinary/fortified foods, parenteral/animal material, and changes in PLP/QST/nerve conduction alone are distinguished separately.
Verification status: Met
Materials actually read: Summary reading: the specified original locations in the currently archived source summaries were actually read. Access to external material types was not attempted, and they were not read in this review.
Why unverified: The inclusion/exclusion conditions for the separate harm question were linked to the actual facet. Clinical treatment efficacy or individual risk rates were not newly assessed.
Reason for missing information: These are not suitable for consolidation into a single risk rate.
Required materials and conditions: Original claim, population/exposure, route, and endpoint boundaries
Materials to obtain first: Original claim, population/exposure, route, and endpoint boundaries
Further research: Compare the roles of material on other routes, treatment of pre-existing disease, and changes in test results against the eligibility boundaries.
Remaining uncertainty: These are not suitable for consolidation into a single risk rate. This status concerns a narrow scope of record/material verification and does not newly assess clinical causality, occurrence probability, or individual safety.
Conditions for verification: Link the original claim to oral supplement/medicine exposure and clinical new-onset/worsening endpoints, and specify the exclusions.
Why this condition is needed: Required to distinguish the harm claim from questions about efficacy for treating pre-existing neuropathy or changes in test results.
Application exceptions: The scope is not extended to food/parenteral exposure, animals, changes in test values alone, or all neuropathy from other causes.
Referenced methods: C01: Question-clarification principles in M03 §3.1, §3.2.1–3.2.4; detailed separation rules are internally designed / C05: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptation to testing are internally designed / H01: M19 §19.1.2–19.2.4; detailed distinctions are internally designed / H09: Chamgap's own interpretation boundaries. M19 principles are referenced; no formal causality tool was applied. Rationale for application to this case: required to distinguish the harm claim from questions about efficacy for treating pre-existing neuropathy or changes in test results. No formal causality/harm grading assessment was performed.

Related sources

N03 · Are the B6 vitamer, salt, and formulation identities established for each source?

Current findings: The preserved manuscript distinguishes pyridoxine, pyridoxine hydrochloride, pyridoxal, PLP/P5P, and pyridoxamine. Although causality is clearest for high-dose pyridoxine, the exact salt in several sources is unverified, and no clinical guarantee that PLP is free of risk was verified.
Verification status: Partly verified
Materials actually read: Summary reading: the specified original locations in the currently archived source summaries were actually read. Access to external material types was not attempted, and they were not read in this review.
Why unverified: The original boundaries distinguishing vitamers are present, but the salt identities/equivalence of risk of all actual formulations are not established.
Reason for missing information: Exact vitamer/salt and equivalence between formulations.
Required materials and conditions: Original formulation composition, vitamer/salt, and product description
Materials to obtain first: Original formulation composition, vitamer/salt, and product description
Further research: Compare the reported substance and actual formulation composition by vitamer.
Remaining uncertainty: Exact vitamer/salt and equivalence between formulations. This status concerns a narrow scope of record/material verification and does not newly assess clinical causality, occurrence probability, or individual safety.
Conditions for verification: Verify the substance and salt actually reported in each source, and leave detailed identity unverified where it is unavailable.
Why this condition is needed: Required to avoid combining different exposures, such as pyridoxine, its hydrochloride, and PLP/P5P, as having the same toxic potency.
Application exceptions: Material reporting only pyridoxine is not filled in as the hydrochloride, and absence of risk for PLP is not inferred.
Referenced methods: C05: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptation to testing are internally designed / H05: Design considerations in M19 §19.2.2–19.2.4; detailed recording of confounding is internally designed. Rationale for application to this case: required to avoid combining different exposures, such as pyridoxine, its hydrochloride, and PLP/P5P, as having the same toxic potency. No formal causality/harm grading assessment was performed.

Related sources S11 S12 S13 S14 S20 S21 S22

N04 · Are the brand, batch, measured content, and actual dose taken verified?

Current findings: Single-ingredient tablets/capsules and combination products are distinguished, but the exact brand, release formulation, purity, batch, measured content versus labeled amount, and actual dosing frequency/total duration are unverified in several sources. These gaps were not filled in as identical formulations or actual total intake.
Verification status: Unverified
Materials actually read: Summary reading: the specified original locations in the currently archived source summaries were actually read. Access to external material types was not attempted, and they were not read in this review.
Why unverified: The currently preserved content explicitly states that these detailed identities and actual amounts used cannot be established.
Reason for missing information: Product/batch, measured amount, frequency, and adherence/duration.
Required materials and conditions: Manufacturing/labeling, batch, measured content, and dosing frequency/adherence records
Materials to obtain first: Manufacturing/labeling, batch, measured content, and dosing frequency/adherence records
Further research: Review whether product information agrees with individual intake records.
Remaining uncertainty: Product/batch, measured amount, frequency, and adherence/duration. This status concerns a narrow scope of record/material verification and does not newly assess clinical causality, occurrence probability, or individual safety.
Conditions for verification: Verify the exact product, ingredients/release, measured content, and actual dosing frequency/adherence, and identify the remaining gaps.
Why this condition is needed: Required to avoid generalizing a nominal administered dose into actual intake or risk for the entire product.
Application exceptions: The labeled tablet/capsule amount is not treated as verification of purity, batch/release, dosing frequency, or adherence.
Referenced methods: C05: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptation to testing are internally designed / E02: M03 §3.2.3, M08 §8.2.2–8.2.3; internal application / H05: Design considerations in M19 §19.2.2–19.2.4; detailed recording of confounding is internally designed. Rationale for application to this case: required to avoid generalizing a nominal administered dose into actual intake or risk for the entire product. No formal causality/harm grading assessment was performed.

Related sources S20 S21 S22 S24 S25

N05 · Can content per tablet be distinguished from actual total daily intake across multiple products?

Current findings: In the 2018 Lareb abstract, 1.4–100 mg is the content per tablet. Of the TGA's 32 selected reports, 9 involved multiple products. Daily total or cumulative intake was not calculated using unverified dosing frequency/measured amounts and overlapping categories.
Verification status: Partly verified
Materials actually read: Summary reading: the specified original locations in the currently archived source summaries were actually read. Access to external material types was not attempted, and they were not read in this review.
Why unverified: The units and the signal involving multiple products are known, but components needed to establish individual actual total/cumulative intake are insufficient.
Reason for missing information: All products, measured/labeled amounts, dosing frequency, and duration for each individual.
Required materials and conditions: Product-specific content units, dosing frequency/number taken, and concurrent-exposure table
Materials to obtain first: Product-specific content units, dosing frequency/number taken, and concurrent-exposure table
Further research: Compare the data units for per-tablet content, per-product content, and total daily intake.
Remaining uncertainty: All products, measured/labeled amounts, dosing frequency, and duration for each individual. This status concerns a narrow scope of record/material verification and does not newly assess clinical causality, occurrence probability, or individual safety.
Conditions for verification: Link content units, number of products, dosing frequency, and background intake, without calculating totals that have not been verified.
Why this condition is needed: Required to avoid converting Lareb's per-tablet content or reports involving multiple products into a daily dose/risk threshold.
Application exceptions: 1.4–100 mg is a per-tablet amount, and the TGA's 9 reports involving multiple products are not an independent group with verified total daily intake.
Referenced methods: C05: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptation to testing are internally designed / E02: M03 §3.2.3, M08 §8.2.2–8.2.3; internal application / H04: M19 §19.1.2–19.2.4; internal application / H05: Design considerations in M19 §19.2.2–19.2.4; detailed recording of confounding is internally designed. Rationale for application to this case: required to avoid converting Lareb's per-tablet content or reports involving multiple products into a daily dose/risk threshold. No formal causality/harm grading assessment was performed.

Related sources S11 S21 S22

N06 · Was oral exposure from supplements/medicines separated from other routes/foods?

Current findings: The facets concern B6 from oral supplements/medicines, with ordinary/fortified foods kept as separate exposure strata. Parenteral/animal doses are not extrapolated to human incidence after oral exposure.
Verification status: Met
Materials actually read: Summary reading: the specified original locations in the currently archived source summaries were actually read. Access to external material types was not attempted, and they were not read in this review.
Why unverified: The condition preserving the actual route and exposure-source boundaries was verified. New harm from other routes was not assessed.
Reason for missing information: An identical risk rate for material outside the specified route is unverified.
Required materials and conditions: Original route, exposure source, and applicability of related material
Materials to obtain first: Original route, exposure source, and applicability of related material
Further research: Compare directness/exclusions according to the original route and exposure stratum.
Remaining uncertainty: An identical risk rate for material outside the specified route is unverified. This status concerns a narrow scope of record/material verification and does not newly assess clinical causality, occurrence probability, or individual safety.
Conditions for verification: Preserve the original exposure strata for oral supplements/medicines and prevent direct extrapolation from other routes.
Why this condition is needed: Required to avoid transferring human incidence after oral exposure across routes and exposure sources.
Application exceptions: Ordinary/fortified foods, parenteral dosing, and animal dosing are not evidence of identical risk for exposure to these formulations.
Referenced methods: C01: Question-clarification principles in M03 §3.1, §3.2.1–3.2.4; detailed separation rules are internally designed / C05: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptation to testing are internally designed / H09: Chamgap's own interpretation boundaries. M19 principles are referenced; no formal causality tool was applied. Rationale for application to this case: required to avoid transferring human incidence after oral exposure across routes and exposure sources. No formal causality/harm grading assessment was performed.

Related sources

N07 · Are the population, pre-exposure neuropathy, and underlying diseases verified for each source?

Current findings: The 5 healthy volunteers, existing CIAP patients/controls, TB cohort treated with terizidone, and 3 older cases represent different populations. Individual baseline renal/hepatic function, medications, and classification as new onset/worsening of existing disease are unverified in several sources.
Verification status: Partly verified
Materials actually read: Summary reading: the specified original locations in the currently archived source summaries were actually read. Access to external material types was not attempted, and they were not read in this review.
Why unverified: The main population contexts are available, but there is no material fully verifying individual baseline status/selection and pre-existing neuropathy.
Reason for missing information: Baseline clinical status, selection, vulnerability, and individual medications.
Required materials and conditions: Table of inclusion/exclusion, baseline symptoms, examination/disease, renal/hepatic status, and medications
Materials to obtain first: Table of inclusion/exclusion, baseline symptoms, examination/disease, renal/hepatic status, and medications
Further research: Review applicability limitations related to baseline risk and population selection.
Remaining uncertainty: Baseline clinical status, selection, vulnerability, and individual medications. This status concerns a narrow scope of record/material verification and does not newly assess clinical causality, occurrence probability, or individual safety.
Conditions for verification: Link the study-specific population, baseline neuropathy, renal/hepatic status, medications, and selection status, and explicitly identify omissions.
Why this condition is needed: Required to avoid combining healthy volunteers, people with existing CIAP, TB/HIV, and older adults into the same population for new-onset events.
Application exceptions: The category of predominantly adults is not converted into normal individual baseline status or safety for special populations.
Referenced methods: C04: M03 §3.2.1; detailed population conditions are internally designed / H05: Design considerations in M19 §19.2.2–19.2.4; detailed recording of confounding is internally designed / H08: M19 §19.1.2–19.2.4; internal application. Rationale for application to this case: required to avoid combining healthy volunteers, people with existing CIAP, TB/HIV, and older adults into the same population for new-onset events. No formal causality/harm grading assessment was performed.

Related sources S20 S23 S24 S25

N08 · Was clinical sensory neuropathy confirmed/ascertained separately from test markers?

Current findings: Clinical new onset/worsening is the primary endpoint, and changes in PLP/QST/nerve conduction alone are excluded. A conflict in the clinical numerator between Berger and EFSA's individual-level extraction and the lack of consistent clinical confirmation in Lareb remain; all participants/reports therefore cannot be treated as equally confirmed events.
Verification status: Partly verified
Materials actually read: Summary reading: the specified original locations in the currently archived source summaries were actually read. Access to external material types was not attempted, and they were not read in this review.
Why unverified: The boundary between clinical events and test findings is defined, but complete comparability/confirmation of diagnosis and ascertainment across sources is unverified.
Reason for missing information: Diagnosis/clinical event table, detection/blinding, and independent interpretation.
Required materials and conditions: Original diagnostic criteria, symptoms/examination, QST/conduction, and detection/blinding procedures
Materials to obtain first: Original diagnostic criteria, symptoms/examination, QST/conduction, and detection/blinding procedures
Further research: Compare clinical event definitions with differences in measurement/detection of test markers.
Remaining uncertainty: Diagnosis/clinical event table, detection/blinding, and independent interpretation. This status concerns a narrow scope of record/material verification and does not newly assess clinical causality, occurrence probability, or individual safety.
Conditions for verification: Verify symptoms, signs/examination, and confirmation/ascertainment procedures, and separate changes in markers alone from clinical events.
Why this condition is needed: Required to avoid substituting changes in PLP/QST/conduction or high blood B6 values for clinical occurrence.
Application exceptions: Participants with changes in test results alone and no clinical symptoms are not included as clinical events.
Referenced methods: C06: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed / E03: M08 Table 8.2.a, M03 §3.2.4; internal application / E09: M03 §3.2.4; internally defined extension boundaries / H01: M19 §19.1.2–19.2.4; detailed distinctions are internally designed. Rationale for application to this case: required to avoid substituting changes in PLP/QST/conduction or high blood B6 values for clinical occurrence. No formal causality/harm grading assessment was performed.

Related sources S14 S20 S21 S22 S25

N09 · Can new onset and worsening of pre-existing symptoms be distinguished separately?

Current findings: The original facet labels material unable to separate the outcomes as having a mixed endpoint. Court's 50 people constitute a mixture of new onset/worsening, and the respective event counts were not verified in the abstract. Lareb also has gaps in clinical confirmation and the distinction between new onset/worsening.
Verification status: Unverified
Materials actually read: Summary reading: the specified original locations in the currently archived source summaries were actually read. Access to external material types was not attempted, and they were not read in this review.
Why unverified: The current archived material cannot establish all separate event counts and denominators for new onset/worsening.
Reason for missing information: Original events, denominators, and baseline status for new onset/worsening separately.
Required materials and conditions: Table of baseline symptoms, event counts for new onset/worsening, populations at risk, and timing
Materials to obtain first: Table of baseline symptoms, event counts for new onset/worsening, populations at risk, and timing
Further research: Trace pre-existing disease and the classification of events before and after exposure.
Remaining uncertainty: Original events, denominators, and baseline status for new onset/worsening separately. This status concerns a narrow scope of record/material verification and does not newly assess clinical causality, occurrence probability, or individual safety.
Conditions for verification: Verify pre-exposure symptoms and events, denominators, and timing for new onset/worsening, and leave mixed outcomes as mixed.
Why this condition is needed: Required to avoid converting results for a mixed endpoint into a single incidence rate of new toxicity.
Application exceptions: The mixture of new onset/worsening in the TB cohort or incomplete classification in spontaneous reports is not filled in as separately available values.
Referenced methods: C06: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed / H01: M19 §19.1.2–19.2.4; detailed distinctions are internally designed / H04: M19 §19.1.2–19.2.4; internal application. Rationale for application to this case: required to avoid converting results for a mixed endpoint into a single incidence rate of new toxicity. No formal causality/harm grading assessment was performed.

Related sources S21 S22 S25

N10 · Were Berger's reported doses separated from observations of onset and after withdrawal?

Current findings: Berger is an uncontrolled prospective exposure study in which 5 volunteers received pyridoxine at 1 or 3 g/day. The preserved account states that symptoms appeared earlier at the higher dose and worsening could continue for 2–3 weeks after withdrawal. Individual cumulative exposure was not calculated.
Verification status: Met
Materials actually read: Summary reading: the specified original locations in the currently archived source summaries were actually read. Access to external material types was not attempted, and they were not read in this review.
Why unverified: The narrow attribution of reported doses and temporal relationships was verified. Clinical event counts/population incidence remain subject to separate unverified/conflicting conditions.
Reason for missing information: Individual actual exposure duration/cumulative exposure and the clinical numerator are separate gaps.
Required materials and conditions: Original table of dosing/onset and follow-up after withdrawal
Materials to obtain first: Original table of dosing/onset and follow-up after withdrawal
Further research: Compare dose, time to onset, and the course after exposure withdrawal separately.
Remaining uncertainty: Individual actual exposure duration/cumulative exposure and the clinical numerator are separate gaps. This status concerns a narrow scope of record/material verification and does not newly assess clinical causality, occurrence probability, or individual safety.
Conditions for verification: Attribute the 5 volunteers, reported pyridoxine doses of 1 or 3 g/day, earlier onset, and worsening for 2–3 weeks after withdrawal to their original locations.
Why this condition is needed: Required to avoid extending temporal relationships at high doses to low doses generally/all users.
Application exceptions: 1 or 3 g/day is not converted into a general recommended dose, minimum risk dose, or individual actual cumulative exposure.
Referenced methods: C05: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptation to testing are internally designed / C06: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed / H02: Design-specific harm questions in M19 §19.2; temporal-relationship details are internally designed. Rationale for application to this case: required to avoid extending temporal relationships at high doses to low doses generally/all users. No formal causality/harm grading assessment was performed.

Related sources S20 S14

N11 · Is Berger's actual number of clinical cases consistently verified across sources?

Current findings: The broad description in Berger's abstract and EFSA's individual-participant extraction disagree on the number of people with onset of clinical symptoms. The EFSA table includes participants with changes in sensory testing alone and no clinical symptoms; therefore, 5/5 or 100% occurrence is not claimed.
Verification status: Conflicting information
Materials actually read: Summary reading: the specified original locations in the currently archived source summaries were actually read. Access to external material types was not attempted, and they were not read in this review.
Why unverified: Descriptions of the same clinical occurrence disagree, so a single numerator cannot be established. This descriptive conflict was not resolved through a new causality judgment.
Reason for missing information: Resolution of conflicts concerning the individual clinical numerator, diagnostic confirmation criteria, and correspondence between extractions.
Required materials and conditions: Correspondence between the original abstract, individual clinical symptom/test table, and EFSA extraction
Materials to obtain first: Correspondence between the original abstract, individual clinical symptom/test table, and EFSA extraction
Further research: Review correspondence of participants/clinical criteria across sources and the disagreement in numerators.
Remaining uncertainty: Resolution of conflicts concerning the individual clinical numerator, diagnostic confirmation criteria, and correspondence between extractions. This status concerns a narrow scope of record/material verification and does not newly assess clinical causality, occurrence probability, or individual safety.
Conditions for verification: Compare symptom/test criteria and clinical numerators in the original abstract and EFSA's individual-participant extraction. If disagreement remains, do not treat the numerator as established or claim 100% occurrence.
Why this condition is needed: Required to avoid automatically interpreting the denominator of 5 volunteers as 5/5 clinical occurrence.
Application exceptions: Distinguish successful recording of the conflict as it stands from a status in which the clinical numerator has been consistently verified.
Referenced methods: C07: M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptations are internally designed / C08: M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses is internally designed / H01: M19 §19.1.2–19.2.4; detailed distinctions are internally designed / H04: M19 §19.1.2–19.2.4; internal application. Rationale for application to this case: required to avoid automatically interpreting the denominator of 5 volunteers as 5/5 clinical occurrence. No formal causality/harm grading assessment was performed.

Related sources S20 S14

N12 · Were the uncontrolled design of the high-dose experiment and the boundaries of comparative risk preserved?

Current findings: Berger is a small prospective high-dose exposure study without an unexposed control. The original weight explicitly states that it serves as evidence for causality of high-dose pyridoxine but is not used as population incidence. This table does not convert it into an RCT or an RR for general users.
Verification status: Met
Materials actually read: Summary reading: the specified original locations in the currently archived source summaries were actually read. Access to external material types was not attempted, and they were not read in this review.
Why unverified: The condition for preserving the actual design and original interpretation limitations was verified. High-dose causality was not newly certified, and comparative risk was not calculated.
Reason for missing information: An unexposed comparison and quantitative risk for general users remain separately unverified.
Required materials and conditions: Original design, comparator/allocation, and exposure table
Materials to obtain first: Original design, comparator/allocation, and exposure table
Further research: Review the scope of causal/risk interpretation permitted by the design and actual comparison conditions.
Remaining uncertainty: An unexposed comparison and quantitative risk for general users remain separately unverified. This status concerns a narrow scope of record/material verification and does not newly assess clinical causality, occurrence probability, or individual safety.
Conditions for verification: Explicitly identify the uncontrolled prospective high-dose design and distinguish it from estimation of population incidence/RR.
Why this condition is needed: Required to avoid converting the temporal relationship of prospective exposure into a randomized comparison with no exposure or a population risk rate.
Application exceptions: Observations at the alternative doses 1 or 3 g are not treated as an RCT effect with an unexposed control.
Referenced methods: C05: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptation to testing are internally designed / E01: M08 §8.1–8.2.3; internal application / H03: M19 §19.2.2–19.2.4, M03 §3.2.3; internal application. Rationale for application to this case: required to avoid converting the temporal relationship of prospective exposure into a randomized comparison with no exposure or a population risk rate. No formal causality/harm grading assessment was performed.

Related sources S20 S14

N13 · Are recovery/worsening after withdrawal and the actual course on rechallenge verified?

Current findings: Official assessments include cases of improvement after withdrawal, but the speed/completeness of recovery is not guaranteed. Worsening for 2–3 weeks after withdrawal of high-dose exposure and the possibility of long-term disability are both preserved. Sufficient individual rechallenge data were not verified in this extraction.
Verification status: Partly verified
Materials actually read: Summary reading: the specified original locations in the currently archived source summaries were actually read. Access to external material types was not attempted, and they were not read in this review.
Why unverified: Some post-withdrawal courses are available, but individual recovery/confirmation through rechallenge and complete follow-up cannot be established.
Reason for missing information: Individual recovery, rechallenge, and completeness of follow-up.
Required materials and conditions: Original individual event records for withdrawal, follow-up/function, and rechallenge
Materials to obtain first: Original individual event records for withdrawal, follow-up/function, and rechallenge
Further research: Compare onset and changes after withdrawal with alternative causes/completeness of follow-up.
Remaining uncertainty: Individual recovery, rechallenge, and completeness of follow-up. This status concerns a narrow scope of record/material verification and does not newly assess clinical causality, occurrence probability, or individual safety.
Conditions for verification: Verify withdrawal/course, completeness of recovery, and rechallenge for each individual, and retain the areas with insufficient information.
Why this condition is needed: Required to avoid extending some improvement into complete recovery for everyone or confirmation through rechallenge.
Application exceptions: Coasting, persistent disability, and cases of recovery after withdrawal are not converted into a guarantee of individual recovery or a probability of permanent damage.
Referenced methods: H02: Design-specific harm questions in M19 §19.2; temporal-relationship details are internally designed / H08: M19 §19.1.2–19.2.4; internal application / H09: Chamgap's own interpretation boundaries. M19 principles are referenced; no formal causality tool was applied. Rationale for application to this case: required to avoid extending some improvement into complete recovery for everyone or confirmation through rechallenge. No formal causality/harm grading assessment was performed.

Related sources S14 S20 S24 S26

N14 · Are the independence and overlap relationships of Lareb reports verified?

Current findings: The 2025 Lareb analysis includes 224 reports and overlaps within the same series with the 2018 count of 90 reports and EFSA's interim counts. The original evidence groups them under F-LAREB and does not sum them. The current archived summary does not contain a table of independent events with individual report overlap resolved.
Verification status: Partly verified
Materials actually read: Summary reading: the specified original locations in the currently archived source summaries were actually read. Access to external material types was not attempted, and they were not read in this review.
Why unverified: Overlap within the series is explicitly stated, but no material fully establishes the correspondence of independence/overlap at the individual-report level.
Reason for missing information: Individual report identification and correspondence of overlapping/independent reports.
Required materials and conditions: Original report identifiers, collection period, and overlap/re-citation correspondence table
Materials to obtain first: Original report identifiers, collection period, and overlap/re-citation correspondence table
Further research: Compare the relationship between reanalysis of the same reports and new independent events.
Remaining uncertainty: Individual report identification and correspondence of overlapping/independent reports. This status concerns a narrow scope of record/material verification and does not newly assess clinical causality, occurrence probability, or individual safety.
Conditions for verification: Link the series, collection period, and overlap relationships, and do not sum counts when individual overlap/independent events are unverified.
Why this condition is needed: Required to avoid adding the 2018/2025/EFSA interim counts as independent reports/trials.
Application exceptions: 90 and 224 overlap within the same reporting series, and official re-citations are not separate replications in humans.
Referenced methods: C02: Distinction between studies and reports in M04 §4.6.1–4.6.2; cohort/outcome linkage is an internal application / E07: M04 §4.6.1–4.6.2, M15 §15.3.1; internal application / H07: M04 §4.6.1–4.6.2; adaptation to harm material is internally designed. Rationale for application to this case: required to avoid adding the 2018/2025/EFSA interim counts as independent reports/trials. No formal causality/harm grading assessment was performed.

Related sources S21 S22 S14

N15 · Were the Lareb collection period and the historical reference dates of the material separated?

Current findings: The manuscript's 2025 Lareb analysis covers reports collected from 2007-08 through 2023-12-31, with 224 reports. The original verified_date is 2026-09-15, distinguished from the local archived-summary review date of 2026-10-05 and the actual report collection window.
Verification status: Met
Materials actually read: Summary reading: the specified original locations in the currently archived source summaries were actually read. Access to external material types was not attempted, and they were not read in this review.
Why unverified: Only the attribution of the original collection period and dates to their events was verified. This did not involve looking up the latest external reports/official regulations.
Reason for missing information: The current latest report collection window/individual exposure durations were not newly verified.
Required materials and conditions: Original analysis collection window and publication/review metadata
Materials to obtain first: Original analysis collection window and publication/review metadata
Further research: Compare the actual event associated with each date and the applicability of the material.
Remaining uncertainty: The current latest report collection window/individual exposure durations were not newly verified. This status concerns a narrow scope of record/material verification and does not newly assess clinical causality, occurrence probability, or individual safety.
Conditions for verification: Preserve the 2025 analysis's report collection window, 2007-08–2023-12-31, separately from publication/review dates.
Why this condition is needed: Required to avoid changing the end date of report collection into the publication/review date or the date of this lookup.
Application exceptions: The report collection end on 2023-12-31, the 2025 analysis, the original review on 2026-09-15, and the date of this review are different events.
Referenced methods: C06: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed / C09: M04 §4.5, §4.6.3; limitations on the current material conversion reflect the user-defined scope and internal design / H02: Design-specific harm questions in M19 §19.2; temporal-relationship details are internally designed. Rationale for application to this case: required to avoid changing the end date of report collection into the publication/review date or the date of this lookup. No formal causality/harm grading assessment was performed.

Related sources S22

N16 · Are clinical confirmation, actual exposure duration, and completeness of collection of Lareb reports verified?

Current findings: Lareb provides a safety signal from spontaneously reported neuropathy. The original evidence/manuscript states that consistent clinical confirmation, actual daily amounts/durations, and separation of new from worsened cases are incomplete. Blood values alone do not establish clinical toxicity in each report.
Verification status: Unverified
Materials actually read: Summary reading: the specified original locations in the currently archived source summaries were actually read. Access to external material types was not attempted, and they were not read in this review.
Why unverified: The currently retained materials contain no original table that would establish confirmation, actual timing, or completeness of detection for each report.
Reason for missing information: Clinical confirmation, exposure/duration, and collection/follow-up for each report.
Required materials and conditions: Original report table of diagnosis/exposure/duration, detection/selection, and follow-up
Materials to obtain first: Original report table of diagnosis/exposure/duration, detection/selection, and follow-up
Further research: Review reporting definitions, selection/detection processes, and individual temporal relationships.
Remaining uncertainty: Clinical confirmation, exposure/duration, and collection/follow-up for each report. This status concerns a narrow scope of record/material verification and does not newly assess clinical causality, occurrence probability, or individual safety.
Conditions for verification: Check the clinical definition/confirmation, exposure/onset periods, alternative causes, and missed detection for each report.
Why this condition is needed: Required to avoid treating reported neuropathy as consistently confirmed new-onset events.
Application exceptions: Blood B6 values or titles are not used to substitute for gaps in report selection, diagnosis, or exposure.
Referenced methods: C06: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptation is internally designed / H01: M19 §19.1.2–19.2.4; detailed distinctions are internally designed / H02: M19 §19.2 design-specific harm questions; details of temporal relationships are internally designed / H06: M19 §19.1.2–19.2.4, M04 §4.6.3; internal application. Rationale for application to this case: needed to avoid treating reported neuropathy as consistently confirmed new clinical events. No formal causality/harm grading assessment was performed.

Related sources S21 S22

N17 · Is a denominator verified for calculating incidence among exposed persons from spontaneous reports?

Current findings: Lareb’s 224 reports and TGA’s 32 reports are report counts. The manuscript states that incidence is not calculated because an exposed-person denominator and consistent clinical confirmation/duration are absent. This table also calculates neither report proportions nor incidence.
Verification status: Unverified
Materials actually read: Summary reading: the specified original locations in the currently archived source summaries were actually read. Access to external material types was not attempted, and they were not read in this review.
Why unverified: Without a population-at-risk denominator and duration, report counts cannot establish incidence among exposed persons.
Reason for missing information: Exposed-person denominator, observation time, and completeness of reporting/confirmation.
Required materials and conditions: Data on all exposed persons, observation time by dose, all/confirmed events, and unreported cases
Materials to obtain first: Data on all exposed persons, observation time by dose, all/confirmed events, and unreported cases
Further research: Review the correspondence between report-based counts and the actual population at risk/observation time.
Remaining uncertainty: Exposed-person denominator, observation time, and completeness of reporting/confirmation. This status concerns a narrow scope of record/material verification and does not newly assess clinical causality, occurrence probability, or individual safety.
Conditions for verification: Do not present incidence unless all exposed persons, observation time, and event counts for the same event/dose/duration have been verified.
Why this condition is needed: Needed to avoid converting report counts into probabilities of occurrence among all users or dose groups.
Application exceptions: Report counts, counts of blood tests, and content per tablet are not exposed-person counts or person-time.
Referenced methods: C07: M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptation is internally designed / H04: M19 §19.1.2–19.2.4; internal application / H09: Chamgap’s own interpretive boundaries. M19 principles are referenced; no formal causality tool was applied. Rationale for application to this case: needed to avoid converting report counts into probabilities of occurrence among all users or dose groups. No formal causality/harm grading assessment was performed.

Related sources S21 S22 S11

N18 · Can selection and overlap in TGA’s 32 reports and low-dose/multiple-product categories be verified?

Current findings: Through 2022-08-05, TGA reported 32 selected reports, of which 21 involved 50 mg/day or less and 9 involved use of multiple products. The categories may overlap. These describe the composition of reports, not the probability of occurrence among users at those doses; an individual-level selection/overlap table is absent from the retained archived summaries.
Verification status: Partly verified
Materials actually read: Summary reading: the specified original locations in the currently archived source summaries were actually read. Access to external material types was not attempted, and they were not read in this review.
Why unverified: The selected report counts/categories and possibility of overlap are known, but the complete selection, confirmation, and overlap correspondence cannot be established.
Reason for missing information: Records of selection/clinical confirmation, category overlap, and omissions.
Required materials and conditions: Original TGA tables of report selection, clinical confirmation, and overlap between dose/multiple-product categories
Materials to obtain first: Original TGA tables of report selection, clinical confirmation, and overlap between dose/multiple-product categories
Further research: Compare selection criteria, category overlap, and detection/reporting bias.
Remaining uncertainty: Records of selection/clinical confirmation, category overlap, and omissions. This status concerns a narrow scope of record/material verification and does not newly assess clinical causality, occurrence probability, or individual safety.
Conditions for verification: Verify the selection criteria, categories/overlap, and actual denominator meanings of 32·21·9, while retaining unverified selection processes as unverified.
Why this condition is needed: Needed to avoid mistaking the composition of selected reports for comparative risk among all users by dose.
Application exceptions: The 21 reports and 9 reports may overlap; the 32 reports are not substituted for all reports/exposed persons or fully confirmed events.
Referenced methods: C04: M03 §3.2.1; detailed population conditions are internally designed / C07: M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptation is internally designed / H04: M19 §19.1.2–19.2.4; internal application / H06: M19 §19.1.2–19.2.4, M04 §4.6.3; internal application. Rationale for application to this case: needed to avoid mistaking the composition of selected reports for comparative risk among all users by dose. No formal causality/harm grading assessment was performed.

Related sources S11 S12

N19 · Are comparative risk, causality, and a no-risk boundary at low doses established?

Current findings: Low-dose spontaneous reports constitute a possible signal, but a minimum risk dose/duration and an individual no-risk boundary have not been verified. The manuscript avoids both confirming causality at all low doses and declaring all low doses safe, and distinguishes these questions from labeling-warning criteria.
Verification status: Unverified
Materials actually read: Summary reading: the specified original locations in the currently archived source summaries were actually read. Access to external material types was not attempted, and they were not read in this review.
Why unverified: Without actual comparative/denominator, exposure, and confirmation data, a causal risk or no-risk boundary applicable to all low doses cannot be established.
Reason for missing information: Precise exposure, comparators, denominators/durations, and clinical/confounding data by dose.
Required materials and conditions: Exposure/comparator, event, duration, confounding, and risk-estimate data for each low dose
Materials to obtain first: Exposure/comparator, event, duration, confounding, and risk-estimate data for each low dose
Further research: Distinguish the evidentiary level of spontaneous-report signals from that of comparative-risk/causal conclusions.
Remaining uncertainty: Precise exposure, comparators, denominators/durations, and clinical/confounding data by dose. This status concerns a narrow scope of record/material verification and does not newly assess clinical causality, occurrence probability, or individual safety.
Conditions for verification: Retain the scope of dose-specific risk verification based on actual comparators/denominators, precise exposure, other causes/duration, and clinical events.
Why this condition is needed: Needed to avoid converting a possible signal from low-dose reports into confirmed causality at all low doses or safety at all low doses.
Application exceptions: The composition of reports involving ≤50 mg/day and the labeling warning for >10 mg are not the same biological threshold.
Referenced methods: H03: M19 §19.2.2–19.2.4, M03 §3.2.3; internal application / H04: M19 §19.1.2–19.2.4; internal application / H09: Chamgap’s own interpretive boundaries. M19 principles are referenced; no formal causality tool was applied. Rationale for application to this case: needed to avoid converting a possible signal from low-dose reports into confirmed causality at all low doses or safety at all low doses. No formal causality/harm grading assessment was performed.

Related sources S11 S12 S14

N20 · Are the dose-specific comparative estimate and its uncertainty in the tuberculosis cohort verified?

Current findings: Court is a terizidone-treatment cohort with 144 people recruited and neuropathy in 50 people (35% in the original). The comparison of 200 versus 150 mg/day retains an adjusted HR of 2.79, P = 0.01, for a mixed new/worsened endpoint. Group-specific denominators/event counts, the HR CI, and exact follow-up duration were not verified from the abstract.
Verification status: Partly verified
Materials actually read: Summary reading: the specified original locations in the currently archived source summaries were actually read. Access to external material types was not attempted, and they were not read in this review.
Why unverified: The nominal-dose comparison and reported HR/P are available, but group-specific denominators and CI/duration are insufficient. No new CI/RR/proportion was calculated.
Reason for missing information: Group-specific events, denominators, HR CI, and follow-up/analysis tables.
Required materials and conditions: Tables of exposure/events, denominators, adjustment models, HR/CI, and follow-up by dose group
Materials to obtain first: Tables of exposure/events, denominators, adjustment models, HR/CI, and follow-up by dose group
Further research: Compare estimates and uncertainty for the same event/comparator/duration and analysis model.
Remaining uncertainty: Group-specific events, denominators, HR CI, and follow-up/analysis tables. This status concerns a narrow scope of record/material verification and does not newly assess clinical causality, occurrence probability, or individual safety.
Conditions for verification: Distinguish the 200 versus 150 mg/day comparison and adjusted HR/P from the actual scope of verification of group-specific denominators/events, CI, and follow-up.
Why this condition is needed: Needed to avoid transferring the reported HR to a causal RR for general supplement use or an exact incidence rate.
Application exceptions: The 144 people and 50 people (35% in the original) and HR 2.79 do not substitute for group-specific denominators/event counts or CI.
Referenced methods: C05: M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptation are internally designed / C07: M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptation is internally designed / E04: M08 §8.2.2, M15 §15.3.1; internal application / E05: M15 §15.3.1–15.3.3; internal application / H03: M19 §19.2.2–19.2.4, M03 §3.2.3; internal application / H04: M19 §19.1.2–19.2.4; internal application. Rationale for application to this case: needed to avoid transferring the reported HR to a causal RR for general supplement use or an exact incidence rate. No formal causality/harm grading assessment was performed.

Related sources S25

N21 · Were the nonrandomized doses in the tuberculosis cohort and limitations on application to general supplement use preserved?

Current findings: The original design is a prospective cohort of multidrug-resistant tuberculosis treated with terizidone; B6 doses are nonrandomized. HIV, tuberculosis, co-medications, and prescribing reasons are intertwined, so the retained HR is not transferred to a causal RR for general supplement users.
Verification status: Met
Materials actually read: Summary reading: the specified original locations in the currently archived source summaries were actually read. Access to external material types was not attempted, and they were not read in this review.
Why unverified: The condition of preserving the actual nonrandomized context and original generalizability limitations was verified. This is not a judgment that confounding was eliminated.
Reason for missing information: A separate causal comparative risk for general supplement users is unverified.
Required materials and conditions: Original recruitment/prescribing, population/concurrent treatment, and actual comparator design
Materials to obtain first: Original recruitment/prescribing, population/concurrent treatment, and actual comparator design
Further research: Review the interpretive scope arising from the population, prescribing context, and nonrandomized comparison.
Remaining uncertainty: A separate causal comparative risk for general supplement users is unverified. This status concerns a narrow scope of record/material verification and does not newly assess clinical causality, occurrence probability, or individual safety.
Conditions for verification: Indicate the original design, population/co-medication, and nonrandomized doses, and prevent transfer of the HR to an RR for general users.
Why this condition is needed: Needed to avoid converting a nonrandomized comparison in a treatment setting into an RCT causal effect among healthy users.
Application exceptions: Do not equate the TB/HIV and terizidone/cycloserine context with general exposure to a single-ingredient supplement.
Referenced methods: C04: M03 §3.2.1; detailed population conditions are internally designed / E01: M08 §8.1–8.2.3; internal application / H03: M19 §19.2.2–19.2.4, M03 §3.2.3; internal application / H05: M19 §19.2.2–19.2.4 design considerations; detailed confounding records are internally designed. Rationale for application to this case: needed to avoid converting a nonrandomized comparison in a treatment setting into an RCT causal effect among healthy users. No formal causality/harm grading assessment was performed.

Related sources S25

N22 · Was confounding by tuberculosis/HIV, medications, and prescribing reasons sufficiently controlled?

Current findings: The manuscript retains the intertwined roles of HIV, TB, co-medications, and prescribing reasons. The reported HR was verified in the abstract, but all adjustment variables, baseline neuropathy, prescribing/adherence, and disease roles cannot be established from the retained archived summaries.
Verification status: Unverified
Materials actually read: Summary reading: the specified original locations in the currently archived source summaries were actually read. Access to external material types was not attempted, and they were not read in this review.
Why unverified: Adjustment tables and actual baseline/prescribing data are insufficient to establish the extent of control for alternative causes other than B6.
Reason for missing information: Adjustment models, baseline/prescribing factors, concurrent exposures, and residual confounding.
Required materials and conditions: Original adjustment-model, prescribing/underlying-disease, medication, and exposure-follow-up data
Materials to obtain first: Original adjustment-model, prescribing/underlying-disease, medication, and exposure-follow-up data
Further research: Review actual measurement of adjustment variables and confounding associated with timing and prescribing.
Remaining uncertainty: Adjustment models, baseline/prescribing factors, concurrent exposures, and residual confounding. This status concerns a narrow scope of record/material verification and does not newly assess clinical causality, occurrence probability, or individual safety.
Conditions for verification: Check model variables, prescribing reasons, baseline status/concurrent medications, exposure deviations, and residual confounding.
Why this condition is needed: Needed to avoid establishing the association with B6 dose as a cause independent of medications and diseases.
Application exceptions: The term adjusted HR alone does not eliminate residual confounding from prescribing indications, baseline neuropathy, or disease/co-medication.
Referenced methods: H05: M19 §19.2.2–19.2.4 design considerations; detailed confounding records are internally designed / C04: M03 §3.2.1; detailed population conditions are internally designed / E02: M03 §3.2.3, M08 §8.2.2–8.2.3; internal application. Rationale for application to this case: needed to avoid establishing the association with B6 dose as a cause independent of medications and diseases. No formal causality/harm grading assessment was performed.

Related sources S25

N23 · Can the endpoint/time denominator for TB neuropathy be separated from other neuropsychiatric AE?

Current findings: Court’s outcome is a mixture of new or worsened peripheral neuropathy. Separate event counts and exact follow-up duration are unverified in the abstract. The person-month incidence of all neuropsychiatric AE was not used as the incidence of this clinical sensory neuropathy.
Verification status: Partly verified
Materials actually read: Summary reading: the specified original locations in the currently archived source summaries were actually read. Access to external material types was not attempted, and they were not read in this review.
Why unverified: Boundaries for the mixed endpoint and exclusion of other AE are present, but event-specific definitions, separate counts/time, and participant flow are incomplete.
Reason for missing information: Separate neuropathy definitions/events, denominators, and duration/missing data.
Required materials and conditions: Neuropathy-specific tables of definitions/confirmation, events/time, and missing data/discontinuation
Materials to obtain first: Neuropathy-specific tables of definitions/confirmation, events/time, and missing data/discontinuation
Further research: Compare attribution of the mixed endpoint, other AE, and observation time/participant flow.
Remaining uncertainty: Separate neuropathy definitions/events, denominators, and duration/missing data. This status concerns a narrow scope of record/material verification and does not newly assess clinical causality, occurrence probability, or individual safety.
Conditions for verification: Separately verify the definition, new/worsened status, follow-up/denominator, and missing data for neuropathy, and prevent transfer of the composite AE incidence.
Why this condition is needed: Needed to avoid transferring the person-month incidence of all neuropsychiatric AE to sensory neuropathy.
Application exceptions: The mixed new/worsened count of 50 people is not a separate count of clinically confirmed new events or an exposure-time denominator.
Referenced methods: C06: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptation is internally designed / H01: M19 §19.1.2–19.2.4; detailed distinctions are internally designed / H04: M19 §19.1.2–19.2.4; internal application / H06: M19 §19.1.2–19.2.4, M04 §4.6.3; internal application. Rationale for application to this case: needed to avoid transferring the person-month incidence of all neuropsychiatric AE to sensory neuropathy. No formal causality/harm grading assessment was performed.

Related sources S25

N24 · Was pre-existing disease in the CIAP case-control study distinguished from the question of new toxicity?

Current findings: Visser is a case-control study of 381 patients with pre-existing CIAP and 140 healthy controls. The original endpoint concerns an association with pre-existing disease, not incident toxicity. The original weight is preserved as limiting/contrary evidence and is not used as a causal incidence rate or a safety guarantee.
Verification status: Met
Materials actually read: Summary reading: the specified original locations in the currently archived source summaries were actually read. Access to external material types was not attempted, and they were not read in this review.
Why unverified: The population/design for the association with pre-existing disease and the boundary against transferring it directly to new-onset risk were verified.
Reason for missing information: This study does not establish a direct comparative risk of new onset by exposure.
Required materials and conditions: Original population/design, baseline symptoms, and exposure timing/endpoints
Materials to obtain first: Original population/design, baseline symptoms, and exposure timing/endpoints
Further research: Compare the directness of the prevalent-case case-control study for the new-onset question and assess reverse causation.
Remaining uncertainty: This study does not establish a direct comparative risk of new onset by exposure. This status concerns a narrow scope of record/material verification and does not newly assess clinical causality, occurrence probability, or individual safety.
Conditions for verification: Indicate the context of the pre-existing CIAP case-control study and its role, which does not establish incident toxicity or guarantee absence of risk.
Why this condition is needed: Needed to avoid converting the association between prevalent CIAP and supplement use into risk of new onset.
Application exceptions: The 381 cases and 140 controls are not a population-at-risk denominator for a cohort with new exposure.
Referenced methods: C04: M03 §3.2.1; detailed population conditions are internally designed / C06: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptation is internally designed / H03: M19 §19.2.2–19.2.4, M03 §3.2.3; internal application / H09: Chamgap’s own interpretive boundaries. M19 principles are referenced; no formal causality tool was applied. Rationale for application to this case: needed to avoid converting the association between prevalent CIAP and supplement use into risk of new onset. No formal causality/harm grading assessment was performed.

Related sources S23

N25 · Were the nonsignificant blood-value result and the supplement-use association in CIAP both preserved?

Current findings: In CIAP, the difference in median blood B6 values of 99 versus 109 nmol/L was nonsignificant at P = 0.58. Supplement use was 31% versus 22%, OR 1.7 (95% CI 1.0–2.7; P = 0.032). Considering daily amounts, cumulative amounts, duration, and blood values, the authors interpreted a causal association as unlikely. Both contrasting and limiting results are preserved.
Verification status: Met
Materials actually read: Summary reading: the specified original locations in the currently archived source summaries were actually read. Access to external material types was not attempted, and they were not read in this review.
Why unverified: Reported values, attribution to different exposures/markers, and the authors’ limiting interpretation were linked together. No new causality/no-risk assessment was performed.
Reason for missing information: Original adjustment/baseline data beyond the scope of the abstract remain separately unverified.
Required materials and conditions: Original results tables, blood-value/supplement-use estimates, and authors’ interpretation
Materials to obtain first: Original results tables, blood-value/supplement-use estimates, and authors’ interpretation
Further research: Compare the results, directions, and uncertainties for different measurements/exposures separately.
Remaining uncertainty: Original adjustment/baseline data beyond the scope of the abstract remain separately unverified. This status concerns a narrow scope of record/material verification and does not newly assess clinical causality, occurrence probability, or individual safety.
Conditions for verification: Link the 381/140 participants’ 99/109 nmol/L values and P, the 31%/22% and OR/CI/P, and the authors’ limiting interpretation together according to their original locations.
Why this condition is needed: Needed to avoid omitting favorable/nonsignificant or contrary results and attributing all neuropathy to B6.
Application exceptions: Do not convert the blood-value P = 0.58 into a risk of 0, or the supplement-use OR into a causal RR for new toxicity.
Referenced methods: C08: M04 §4.6.3, M15 §15.3.1–15.3.3; status separation is internally designed / H09: Chamgap’s own interpretive boundaries. M19 principles are referenced; no formal causality tool was applied. Rationale for application to this case: needed to avoid omitting favorable/nonsignificant or contrary results and attributing all neuropathy to B6. No formal causality/harm grading assessment was performed.

Related sources S23 S14

N26 · Are reverse causation and alternative causes in CIAP and reports sufficiently verified?

Current findings: The manuscript retains possible reverse causation from supplement use prompted by CIAP symptoms and the selected phenotype. Other causes, including diabetes, B12 deficiency, alcohol, kidney disease, and anticancer/TB medications, also need to be considered. Whether these alternatives were sufficiently excluded in each source is unverified.
Verification status: Unverified
Materials actually read: Summary reading: the specified original locations in the currently archived source summaries were actually read. Access to external material types was not attempted, and they were not read in this review.
Why unverified: Specific data on temporal order/baseline status and alternative causes are insufficient to establish elimination of reverse causation/confounding.
Reason for missing information: Data on symptom/use sequence, alternative diseases/medications, and selection/detection.
Required materials and conditions: Baseline symptoms, start/sequence of use, examinations/other tests, and alternative diseases/medications
Materials to obtain first: Baseline symptoms, start/sequence of use, examinations/other tests, and alternative diseases/medications
Further research: Review reverse causation/confounding associated with exposure timing and disease selection/detection.
Remaining uncertainty: Data on symptom/use sequence, alternative diseases/medications, and selection/detection. This status concerns a narrow scope of record/material verification and does not newly assess clinical causality, occurrence probability, or individual safety.
Conditions for verification: Check the temporal order of symptoms/exposure, underlying disease/concurrent medication, selection/measurement, and alternative causes.
Why this condition is needed: Needed to review the possibility that B6 was used because of pre-existing symptoms, and neuropathy due to other causes.
Application exceptions: Elevated PLP or supplement use alone does not establish B6 causation or the cause of pre-existing disease.
Referenced methods: H05: M19 §19.2.2–19.2.4 design considerations; detailed confounding records are internally designed / H06: M19 §19.1.2–19.2.4, M04 §4.6.3; internal application / C04: M03 §3.2.1; detailed population conditions are internally designed. Rationale for application to this case: needed to review the possibility that B6 was used because of pre-existing symptoms, and neuropathy due to other causes. No formal causality/harm grading assessment was performed.

Related sources S23 S14 S21 S22 S25

N27 · Can the combination product and actual long-term exposure in 3 older adults be verified?

Current findings: Kulkantrakorn is a case series of people aged 80·83·83 years, 3 in total, with sensory ataxic neuropathy/gait impairment. They used pyridoxine in B1/B6/B12 combination tablets at 600 mg/day for 3–10 years. The exact formulation, actual cumulative amount, and all underlying causes cannot be established from the current extraction.
Verification status: Partly verified
Materials actually read: Summary reading: the specified original locations in the currently archived source summaries were actually read. Access to external material types was not attempted, and they were not read in this review.
Why unverified: The population, combination/nominal dose, and duration are available, but verification of detailed product information, actual use, and underlying causes is insufficient.
Reason for missing information: Case-specific combination composition, actual use/cumulative exposure, and underlying causes.
Required materials and conditions: Original case-specific product/composition, dose/duration, baseline-status, and adherence data
Materials to obtain first: Original case-specific product/composition, dose/duration, baseline-status, and adherence data
Further research: Compare actual exposure in each case and the combination-product/older-adult context.
Remaining uncertainty: Case-specific combination composition, actual use/cumulative exposure, and underlying causes. This status concerns a narrow scope of record/material verification and does not newly assess clinical causality, occurrence probability, or individual safety.
Conditions for verification: Distinguish combination composition, nominal pyridoxine dose, and duration/population from gaps in actual product, adherence, and concurrent exposure data.
Why this condition is needed: Needed to avoid combining cases involving B1/B6/B12 combination tablets into population incidence for single-ingredient B6 products.
Application exceptions: Ages 80·83·83 years in 3 people and 600 mg/day for 3–10 years do not constitute an exposed-person denominator for a single-ingredient product or an individual recommended dose.
Referenced methods: C05: M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptation are internally designed / H05: M19 §19.2.2–19.2.4 design considerations; detailed confounding records are internally designed / H08: M19 §19.1.2–19.2.4; internal application. Rationale for application to this case: needed to avoid combining cases involving B1/B6/B12 combination tablets into population incidence for single-ingredient B6 products. No formal causality/harm grading assessment was performed.

Related sources S24

N28 · Are individual recovery/disability assessments and long-term follow-up in the older-adult cases sufficiently verified?

Current findings: The 3 older-adult cases were reported to show no significant improvement in neuropathy or gait even 2 years after withdrawal. The original weight is a warning of possible persistent harm and explicitly states that a probability of permanent damage cannot be calculated. Verification of complete individual assessments/follow-up data beyond the abstract is insufficient.
Verification status: Partly verified
Materials actually read: Summary reading: the specified original locations in the currently archived source summaries were actually read. Access to external material types was not attempted, and they were not read in this review.
Why unverified: The course is reported, but follow-up, denominator, and assessment data to establish individual probabilities of permanent damage/recovery are absent.
Reason for missing information: Individual long-term function, follow-up, causes, and risk denominators.
Required materials and conditions: Original withdrawal/follow-up, neurological/gait assessments, alternative causes, and long-term denominators
Materials to obtain first: Original withdrawal/follow-up, neurological/gait assessments, alternative causes, and long-term denominators
Further research: Review recovery speed/completeness and limitations of follow-up and alternative-cause assessment.
Remaining uncertainty: Individual long-term function, follow-up, causes, and risk denominators. This status concerns a narrow scope of record/material verification and does not newly assess clinical causality, occurrence probability, or individual safety.
Conditions for verification: Compare the scope of verification of original neurological/gait assessments, alternative causes, individual follow-up, and completeness of recovery. A summary stating that there was no significant improvement even 2 years after withdrawal is not treated as verification of a complete long-term assessment or a probability of permanent damage.
Why this condition is needed: Needed to avoid converting cases with no significant improvement 2 years after withdrawal into a probability of permanent damage or inability to recover in everyone.
Application exceptions: No significant improvement is not equivalent to confirmed complete permanent damage, a quantitative incidence rate, or recovery outcomes under other exposures.
Referenced methods: H02: M19 §19.2 design-specific harm questions; details of temporal relationships are internally designed / H04: M19 §19.1.2–19.2.4; internal application / H08: M19 §19.1.2–19.2.4; internal application / H09: Chamgap’s own interpretive boundaries. M19 principles are referenced; no formal causality tool was applied. Rationale for application to this case: needed to avoid converting cases with no significant improvement 2 years after withdrawal into a probability of permanent damage or inability to recover in everyone. No formal causality/harm grading assessment was performed.

Related sources S24

N29 · Are the original results of candidates concerning recovery, absence of neuropathy, and high doses verified?

Current findings: The recovery case S26, the title concerning absence of neuropathy during homocystinuria treatment S27, and pyridoxine abuse S28 are retained as candidates whose original full texts/complete abstracts were not acquired. Quantitative values, safety, and causality were not filled in from titles/metadata alone, and the captcha/fetch failures at that time are not relabeled as failures during this task.
Verification status: Unverified
Materials actually read: Summary reading: the specified original locations in the currently archived source summaries were actually read. Access to external material types was not attempted, and they were not read in this review.
Why unverified: The retained archived summaries lack sufficient abstracts/full texts to verify original clinical results, exposure, and denominators.
Reason for missing information: Actual original results, exposure/denominators, and diagnosis/follow-up for each candidate.
Required materials and conditions: S26/S27/S28 original abstracts/full texts and case/results tables
Materials to obtain first: S26/S27/S28 original abstracts/full texts and case/results tables
Further research: Compare candidate identity/access scope with the feasibility of extracting actual original results.
Remaining uncertainty: Actual original results, exposure/denominators, and diagnosis/follow-up for each candidate. This status concerns a narrow scope of record/material verification and does not newly assess clinical causality, occurrence probability, or individual safety.
Conditions for verification: Use only the actually verified scope of original results/populations, doses, durations, and confirmation; leave title/metadata candidates unverified.
Why this condition is needed: Needed to avoid using titles of inaccessible sources as confirmed positive/negative findings or quantitative contrary evidence.
Application exceptions: Do not convert S26/S27/S28 historical metadata/access failures into failures during this task, an effect of 0, or complete case tables.
Referenced methods: C03: M04 §4.5–4.6 data-collection/selection principles; separation of access from reading and the hyperlink contract are internally designed / C08: M04 §4.6.3, M15 §15.3.1–15.3.3; status separation is internally designed / C09: M04 §4.5, §4.6.3; limitations of the current material conversion follow the user’s scope and internal design / H07: M04 §4.6.1–4.6.2; adaptation for harm materials is internally designed. Rationale for application to this case: needed to avoid using titles of inaccessible sources as confirmed positive/negative findings or quantitative contrary evidence. No formal causality/harm grading assessment was performed.

Related sources S26 S27 S28

N30 · Can original observations for this harm endpoint be traced in copies of the same Levin paper?

Current findings: S01/S02 refer to The influence of pyridoxine in diabetic peripheral neuropathy with the same DOI 10.2337/diacare.4.6.606 and PMID 6751736. The original citation records abstract/author-copy access locations, but the 6 evidence entries in the current source lack a detailed array of this paper’s harm events, denominators, and exposures. Figures from another efficacy manuscript were not borrowed.
Verification status: Unverified
Materials actually read: Summary reading: the specified original locations in the currently archived source summaries were actually read. Access to external material types was not attempted, and they were not read in this review.
Why unverified: Only the same-bibliography relationship is verified; the original observations/denominators for this clinical harm endpoint cannot be established from the currently archived summaries.
Reason for missing information: Actual original values for this paper’s harm events, exposure/baseline status, denominators, and durations.
Required materials and conditions: Tables of actual harm events, baseline status/exposure, and denominators/durations in that paper
Materials to obtain first: Tables of actual harm events, baseline status/exposure, and denominators/durations in that paper
Further research: Compare the copy/abstract relationship and the scope for direct extraction of these new/worsened clinical events.
Remaining uncertainty: Actual original values for this paper’s harm events, exposure/baseline status, denominators, and durations. This status concerns a narrow scope of record/material verification and does not newly assess clinical causality, occurrence probability, or individual safety.
Conditions for verification: Indicate the same-paper/copy relationship and do not fill in harm events, denominators, or doses/durations that are not currently retained.
Why this condition is needed: Needed to avoid borrowing values from treatment evidence for pre-existing diabetic neuropathy and figures from the adjacent manuscript for this new harm table.
Application exceptions: S01/S02 are bibliographic/author copies with the same DOI/PMID, but the 6 evidence entries in source contain no detailed rows for those harm events.
Referenced methods: C01: M03 §3.1, §3.2.1–3.2.4 question-clarification principles; detailed separation rules are internally designed / C02: M04 §4.6.1–4.6.2 distinction between studies and reports; cohort/outcome linkage is an internal application / C03: M04 §4.5–4.6 data-collection/selection principles; separation of access from reading and the hyperlink contract are internally designed / H09: Chamgap’s own interpretive boundaries. M19 principles are referenced; no formal causality tool was applied. Rationale for application to this case: needed to avoid borrowing values from treatment evidence for pre-existing diabetic neuropathy and figures from the adjacent manuscript for this new harm table. No formal causality/harm grading assessment was performed.

Related sources S01 S02

N31 · Were official assessments and re-citations excluded from counts of new independent human trials?

Current findings: The original evidence distinguishes 6 families: Berger/Lareb/TGA/Visser/Kulkantrakorn/Court. EFSA cites Berger and Lareb again; NIH provides official background, and TGA provides selected-report/regulatory documents. S01/S02 copies of the same paper and official documents are not added together as independent trials.
Verification status: Met
Materials actually read: Summary reading: the specified original locations in the currently archived source summaries were actually read. Access to external material types was not attempted, and they were not read in this review.
Why unverified: The condition of preserving the roles of documents/copies and report families was verified. The 6 families were not declared to be 6 independent clinical trials or a count of confirmed events.
Reason for missing information: Complete independence/overlap correspondence of individual original materials remains separately unverified.
Required materials and conditions: Citation lineage in the original official documents, underlying reports, and native family/linked-source lists
Materials to obtain first: Citation lineage in the original official documents, underlying reports, and native family/linked-source lists
Further research: Trace re-citations/reanalyses of original experiments/reports and the roles of official documents.
Remaining uncertainty: Complete independence/overlap correspondence of individual original materials remains separately unverified. This status concerns a narrow scope of record/material verification and does not newly assess clinical causality, occurrence probability, or individual safety.
Conditions for verification: Link each official document’s background/regulatory/re-citation role to the native evidence families, without issuing an independent count of human studies or participants.
Why this condition is needed: Needed to avoid inflating counts of TGA/NIH/EFSA documents and re-citations of existing reports/experiments into independent replications.
Application exceptions: The authority of an official document does not substitute for individual events, access to original sources, or risk rates.
Referenced methods: C02: M04 §4.6.1–4.6.2 distinction between studies and reports; cohort/outcome linkage is an internal application / H07: M04 §4.6.1–4.6.2; adaptation for harm materials is internally designed / H09: Chamgap’s own interpretive boundaries. M19 principles are referenced; no formal causality tool was applied. Rationale for application to this case: needed to avoid inflating counts of TGA/NIH/EFSA documents and re-citations of existing reports/experiments into independent replications. No formal causality/harm grading assessment was performed.

Related sources S01 S02 S11 S12 S13 S14 S20 S21 S22

N32 · Are comparative risk, CI, and background risk applicable to all users verified?

Current findings: The original assessment supports causality for high-dose pyridoxine but states that the risk rate among all users is unverified. Spontaneous reports lack an exposed-person denominator, and the TB HR/CIAP OR have separate contexts. No overall RR/RD/incidence, CI, NNH, or pooled estimate is calculated.
Verification status: Unverified
Materials actually read: Summary reading: the specified original locations in the currently archived source summaries were actually read. Access to external material types was not attempted, and they were not read in this review.
Why unverified: There are no data establishing comparisons, denominators/durations, and risk estimates for all users addressing the same question.
Reason for missing information: Vitamer, formulation/population, event/comparator, denominator, and duration/CI.
Required materials and conditions: Actual exposed/unexposed, event/denominator, follow-up, RR/RD/CI, and background-risk data
Materials to obtain first: Actual exposed/unexposed, event/denominator, follow-up, RR/RD/CI, and background-risk data
Further research: Review the applicability of estimates, uncertainty, and absolute risk by population/formulation/duration.
Remaining uncertainty: Vitamer, formulation/population, event/comparator, denominator, and duration/CI. This status concerns a narrow scope of record/material verification and does not newly assess clinical causality, occurrence probability, or individual safety.
Conditions for verification: Retain the scope of verification of comparative estimates for the same vitamer/formulation, population, event, comparator, duration, and denominator/CI.
Why this condition is needed: Needed to avoid combining high-dose causality, cases/reports, and an HR from a special population into a single overall risk rate.
Application exceptions: Do not newly calculate a common RR/RD/NNH from case counts, OR, HR, and nutritional/sales criteria.
Referenced methods: C07: M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptation is internally designed / E05: M15 §15.3.1–15.3.3; internal application / H03: M19 §19.2.2–19.2.4, M03 §3.2.3; internal application / H04: M19 §19.1.2–19.2.4; internal application / H09: Chamgap’s own interpretive boundaries. M19 principles are referenced; no formal causality tool was applied. Rationale for application to this case: needed to avoid combining high-dose causality, cases/reports, and an HR from a special population into a single overall risk rate. No formal causality/harm grading assessment was performed.

Related sources S20 S21 S22 S23 S25

N33 · Are form-specific long-term risks in vulnerable groups and pre-existing neuropathy verified?

Current findings: Form-specific toxicity incidence/individual safe doses have not been verified in renal or hepatic impairment, pregnancy/lactation, children, or pre-existing neuropathy. Low B6 indicators in renal disease are not converted into high-dose safety, and contexts requiring a separate treatment benefit–risk assessment are preserved.
Verification status: Unverified
Materials actually read: Summary reading: the specified original locations in the currently archived source summaries were actually read. Access to external material types was not attempted, and they were not read in this review.
Why unverified: The manuscript explicitly identifies gaps in actual population-specific incidence/doses and long-term evidence.
Reason for missing information: Actual formulations, exposure/denominators, and baseline/long-term events by population.
Required materials and conditions: Population-specific formulation, baseline status, exposure, long-term event/follow-up, and treatment-context data
Materials to obtain first: Population-specific formulation, baseline status, exposure, long-term event/follow-up, and treatment-context data
Further research: Review special populations/treatment contexts and the applicability of existing evidence.
Remaining uncertainty: Actual formulations, exposure/denominators, and baseline/long-term events by population. This status concerns a narrow scope of record/material verification and does not newly assess clinical causality, occurrence probability, or individual safety.
Conditions for verification: Check actual exposure/long-term event data and applicability limitations for kidney/liver function, pregnancy/lactation, children, and pre-existing neuropathy.
Why this condition is needed: Needed to avoid extending adult high-dose/report signals to individual safety/risk rates in children, pregnancy, or kidney disease.
Application exceptions: Kidney disease with low B6 markers or deficiency/metabolic disease requiring treatment does not constitute evidence of high-dose safety.
Referenced methods: C04: M03 §3.2.1; detailed population criteria are internally designed / E08: M03 §3.2.1–3.2.4; details on dose, duration, and effect modification are internally designed / H08: M19 §19.1.2–19.2.4; internal application. Reason for application to this case: Needed to avoid extending adult high-dose evidence/reporting signals to individual safety/risk rates in children, pregnancy, or renal disease. No formal causality/harm grading assessment was performed.

Related sources S13 S14 S24 S26 S27

N34 · Are the minimum risk dose/duration, individual no-risk boundary, and cumulative exposure established?

Current findings: An established minimum risk dose/duration and individual no-risk boundary have not been verified. Individual actual daily doses, duration, and adherence were insufficiently documented, so cumulative intake was not calculated in the manuscript either. This table creates no new conversions or minimum safety/risk thresholds.
Verification status: Unverified
Materials actually read: Summary reading: the specified original locations in the currently archived source summaries were actually read. Access to external material types was not attempted, and they were not read in this review.
Why unverified: The actual components and comparative risk data needed to establish a threshold or cumulative exposure are unavailable.
Reason for missing information: Actual daily doses, duration/adherence, events/denominators, and risk comparisons.
Required materials and conditions: Individual measured amounts/doses, duration/adherence, events, and comparison/denominator data
Materials to obtain first: Individual measured amounts/doses, duration/adherence, events, and comparison/denominator data
Further research: Review the actual links between dose, duration, cumulative exposure, and onset/background risk.
Remaining uncertainty: Actual daily doses, duration/adherence, events/denominators, and risk comparisons. This status concerns a narrow scope of record/material verification and does not newly assess clinical causality, occurrence probability, or individual safety.
Conditions for verification: Do not present a threshold/cumulative exposure unless individual actual daily doses, duration/adherence, clinical events, and adequate risk comparisons have been verified.
Why this condition is needed: Needed to avoid turning unverified daily dose × duration into a new cumulative exposure or no-risk threshold.
Application exceptions: The dose–onset relationship at high doses and signals from low-dose reports represent different levels of evidence.
Referenced methods: C05: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptation for tests are internally designed / C06: M03 §3.2.4, M15 §15.3.1–15.3.3; adaptation of outcomes to each question is internally designed / H02: M19 §19.2 on design-specific harm questions; details of temporal relationships are internally designed / H04: M19 §19.1.2–19.2.4; internal application / H09: Chamgap's own interpretation boundaries. M19 principles are referenced; no formal causality tool was applied. Reason for application to this case: Needed to avoid turning unverified daily dose × duration into a new cumulative exposure or no-risk threshold. No formal causality/harm grading assessment was performed.

Related sources S14 S20 S21 S22

N35 · Have the jurisdictions/purposes of the FNB/EFSA upper intake levels been distinguished from clinical toxicity thresholds?

Current findings: The preserved FNB adult UL is 100 mg/day, and the EFSA adult UL is 12 mg/day; these also apply to pregnant/lactating adults. The jurisdictions and assessment methods differ, and the values are not therapeutic dose recommendations, clinical toxicity thresholds, or guarantees of no risk below them. The latest official regulations were not looked up in this review.
Verification status: Met
Materials actually read: Summary reading: the specified original locations in the currently archived source summaries were actually read. Access to external material types was not attempted, and they were not read in this review.
Why unverified: The preserved upper intake values and the condition for distinguishing jurisdictions/purposes were verified. This was not an assessment of new regulations or individual safety.
Reason for missing information: The latest official editions/regulatory updates were not looked up in this review.
Required materials and conditions: Preserved FNB/EFSA editions, populations/risk assessments, and basis for UL derivation
Materials to obtain first: Preserved FNB/EFSA editions, populations/risk assessments, and basis for UL derivation
Further research: Compare jurisdictions/purposes, editions/populations, and the roles of clinical risk evidence.
Remaining uncertainty: The latest official editions/regulatory updates were not looked up in this review. This status concerns a narrow scope of record/material verification and does not newly assess clinical causality, occurrence probability, or individual safety.
Conditions for verification: State the jurisdictions/methods, populations, and nutritional purposes of the preserved editions, and do not repurpose them as therapeutic doses, clinical thresholds, or no-risk guarantees.
Why this condition is needed: Needed to avoid turning a nutritional upper intake level into an individual therapeutic dose recommendation/no-risk guarantee.
Application exceptions: The US 100 mg/day and EFSA 12 mg/day are not clinical comparative values obtained from the same harm study.
Referenced methods: C09: M04 §4.5, §4.6.3; limitations on the current material conversion reflect the user's scope and internal design / H08: M19 §19.1.2–19.2.4; internal application / H09: Chamgap's own interpretation boundaries. M19 principles are referenced; no formal causality tool was applied. Reason for application to this case: Needed to avoid turning a nutritional upper intake level into an individual therapeutic dose recommendation/no-risk guarantee. No formal causality/harm grading assessment was performed.

Related sources S13 S14

N36 · Have TGA label warnings been distinguished from biological risk boundaries?

Current findings: The manuscript records Australia's label warning for supplemental medicines providing daily B6 >10 mg and the 2023-03-01 transition deadline. These are preserved as labeling rules in force on 2026-09-15 and are not turned into a biological boundary at which risk begins or a new regulatory lookup in this review.
Verification status: Met
Materials actually read: Summary reading: the specified original locations in the currently archived source summaries were actually read. Access to external material types was not attempted, and they were not read in this review.
Why unverified: The boundaries of the original labeling/date records and the prohibition on repurposing them as clinical thresholds were verified.
Reason for missing information: Verification of the latest labeling/regulations was not attempted in this review.
Required materials and conditions: Preserved TGA label warning sections, transition/application dates, and products covered
Materials to obtain first: Preserved TGA label warning sections, transition/application dates, and products covered
Further research: Distinguish the roles and dates of administrative labeling and clinical risk evidence.
Remaining uncertainty: Verification of the latest labeling/regulations was not attempted in this review. This status concerns a narrow scope of record/material verification and does not newly assess clinical causality, occurrence probability, or individual safety.
Conditions for verification: Specify the labeling purpose, jurisdiction, application reference date/transition date, and do not use them as clinical risk thresholds.
Why this condition is needed: Needed to avoid mistaking a labeling criterion for the point at which risk begins/an individual safety boundary.
Application exceptions: >10 mg/day and the 2023-03-01 transition deadline are administrative events under the rules preserved as of 2026-09-15.
Referenced methods: C09: M04 §4.5, §4.6.3; limitations on the current material conversion reflect the user's scope and internal design / H09: Chamgap's own interpretation boundaries. M19 principles are referenced; no formal causality tool was applied. Reason for application to this case: Needed to avoid mistaking a labeling criterion for the point at which risk begins/an individual safety boundary. No formal causality/harm grading assessment was performed.

Related sources S11

N37 · Has the future TGA sales classification been distinguished from current prescription/labeling rules?

Current findings: Australia's transition to pharmacist control for products providing more than 50 mg/day–up to and including 200 mg/day is scheduled for 2027-06-01 and was a future regulation as of 2026-09-15. It is distinguished from prescription control above 200 mg/day. Labeling/sales/nutritional ULs are different rules and are not clinical toxicity boundaries.
Verification status: Met
Materials actually read: Summary reading: the specified original locations in the currently archived source summaries were actually read. Access to external material types was not attempted, and they were not read in this review.
Why unverified: The purposes and date attribution of the original scheduled/current rules were distinguished. Their implementation/latest status was not looked up in this review.
Reason for missing information: Verification of the latest sales regulations was not attempted in this review.
Required materials and conditions: Preserved TGA sections on sales classification/effective dates and products covered
Materials to obtain first: Preserved TGA sections on sales classification/effective dates and products covered
Further research: Compare current/future application dates and the purposes of sales, labeling, and nutritional criteria.
Remaining uncertainty: Verification of the latest sales regulations was not attempted in this review. This status concerns a narrow scope of record/material verification and does not newly assess clinical causality, occurrence probability, or individual safety.
Conditions for verification: At the reference date 2026-09-15, separately state the scheduled 2027-06-01 date, dose ranges, and sales purposes.
Why this condition is needed: Needed to avoid retroactively treating regulations scheduled for 2027 as current rules/clinically safe doses in 2026.
Application exceptions: Pharmacist control at >50–≤200 mg/day and prescription control at >200 mg/day are neither nutritional ULs nor equivalent risk categories.
Referenced methods: C09: M04 §4.5, §4.6.3; limitations on the current material conversion reflect the user's scope and internal design / H09: Chamgap's own interpretation boundaries. M19 principles are referenced; no formal causality tool was applied. Reason for application to this case: Needed to avoid retroactively treating regulations scheduled for 2027 as current rules/clinically safe doses in 2026. No formal causality/harm grading assessment was performed.

Related sources S12

N38 · Is the actual scope of verification of funding, product supply, and conflicts of interest known for each report?

Current findings: Lareb 2018 includes a statement of no funding for preparation, while the complete funding for 2025 is unverified. For Visser, only EFSA's mention of foundation support is available, and verification of the original roles is insufficient. Court's PubMed record indexes NIH/NIAID·Wellcome support, but the complete sponsor roles/product supply are unverified. Funding for Berger and the elderly cases is also unverified.
Verification status: Partly verified
Materials actually read: Summary reading: the specified original locations in the currently archived source summaries were actually read. Access to external material types was not attempted, and they were not read in this review.
Why unverified: Some declarations/indexing and official activities are documented, but material establishing the complete funding/supply/roles for each report is unavailable.
Reason for missing information: Original funding/COI, product supply, and research/reporting roles.
Required materials and conditions: Original funding/COI, product supply, and design/analysis/reporting role declarations
Materials to obtain first: Original funding/COI, product supply, and design/analysis/reporting role declarations
Further research: Compare each report's support/declarations with the scope of verification of actual research/product roles.
Remaining uncertainty: Original funding/COI, product supply, and research/reporting roles. This status concerns a narrow scope of record/material verification and does not newly assess clinical causality, occurrence probability, or individual safety.
Conditions for verification: Distinguish each report's actual declarations/indexing from unverified funding, supply/roles, and conflicts of interest.
Why this condition is needed: Needed to avoid filling in indexed grants or unverified information as no funding/no industry involvement/independence.
Application exceptions: The 2018 no-funding statement, unverified 2025 funding, and NIH/Wellcome indexed support are not at the same level of verification.
Referenced methods: C10: Chamgap's own conditions for independence and attribution. The official methodology sections used in this pilot do not endorse all of these detailed items. Reason for application to this case: Needed to avoid filling in indexed grants or unverified information as no funding/no industry involvement/independence. No formal causality/harm grading assessment was performed.

Related sources S20 S21 S22 S23 S24 S25

N39 · Is the actual scope of verification of registration, plans, and corrections/retractions sufficiently established?

Current findings: The registry_id values in the 15 citations are empty, and the manuscript limits registration/correction/retraction searches to the recorded scope. The manuscript states that detailed search/access/selection records are in the delivery package, but the ZIP/separate logs referred to there were not read in the review described in that record. No new determination is made that registration is absent or that the entire literature has integrity.
Verification status: Unverified
Materials actually read: Summary reading: the specified original locations in the currently archived source summaries were actually read. Access to external material types was not attempted, and they were not read in this review.
Why unverified: The currently preserved archived summaries alone cannot establish the full scope of plans/registration or actual detailed search and change/correction/retraction verification.
Reason for missing information: Original registration/plans, changes, and correction/retraction search/publication records.
Required materials and conditions: Registration, protocol/SAP, changes, and correction/retraction search logs/original publication records
Materials to obtain first: Registration, protocol/SAP, changes, and correction/retraction search logs/original publication records
Further research: Compare advance plans/changes and original reports with the scope of searches/access.
Remaining uncertainty: Original registration/plans, changes, and correction/retraction search/publication records. This status concerns a narrow scope of record/material verification and does not newly assess clinical causality, occurrence probability, or individual safety.
Conditions for verification: Verify actual registration/protocols, data collection/SAP, changes, correction/retraction searches, and their scope, and leave unavailable original logs unverified.
Why this condition is needed: Needed to avoid extending unverified information/the recorded search scope into absence of preregistration, absence of corrections, or integrity of the entire literature.
Application exceptions: An empty registry_id is not proof of no registration, and the search_record wording is not evidence that the search logs were actually read in this review.
Referenced methods: C09: M04 §4.5, §4.6.3; limitations on the current material conversion reflect the user's scope and internal design / E06: M08 Table 8.2.a, M04 §4.6.3; internal application / H06: M19 §19.1.2–19.2.4, M04 §4.6.3; internal application. Reason for application to this case: Needed to avoid extending unverified information/the recorded search scope into absence of preregistration, absence of corrections, or integrity of the entire literature. No formal causality/harm grading assessment was performed.

Related sources S20 S21 S22 S23 S24 S25

N40 · Have the current summary reading, historical access to originals, and review/access dates been distinguished?

Current findings: The KO/EN text, 6 evidence entries/15 bibliographic entries, assessments, and metadata in the current source were actually read. Access to all external originals/official pages, registrations, and old separate files was not attempted, and these were not acquired or read in this review. Historical access_level/location remain unchanged; individual access-date keys are absent, leaving empty values, and the original verified_date 2026-09-15 is distinguished solely as the review date.
Verification status: Met
Materials actually read: Summary reading: the specified original locations in the currently archived source summaries were actually read. Access to external material types was not attempted, and they were not read in this review.
Why unverified: The narrow record condition distinguishing actual local reading in this review from historical/external unread materials and dates was verified.
Reason for missing information: Actual verification of external full texts/underlying data was not performed in this review.
Required materials and conditions: Original bytes of the currently preserved archived summaries, citation access locations/identities, and access-date records
Materials to obtain first: Original bytes of the currently preserved archived summaries, citation access locations/identities, and access-date records
Further research: Compare material types, original locations, historical/current reading events, and dates.
Remaining uncertainty: Actual verification of external full texts/underlying data was not performed in this review. This status concerns a narrow scope of record/material verification and does not newly assess clinical causality, occurrence probability, or individual safety.
Conditions for verification: Record the actual local summary locations/SHA separately from external access not attempted/materials unread, historical material types/access, and empty per-report access dates.
Why this condition is needed: Needed to avoid upgrading the reading of preserved archived summaries to reading original full-text papers in this review.
Application exceptions: Do not reuse citations' historical access_level/location or the global verified_date as current full-text access/individual access dates.
Referenced methods: C03: M04 §4.5–4.6 principles for material collection/selection; separation of access and reading and the hyperlink contract are internally designed / C09: M04 §4.5, §4.6.3; limitations on the current material conversion reflect the user's scope and internal design. Reason for application to this case: Needed to avoid upgrading the reading of preserved archived summaries to reading original full-text papers in this review. No formal causality/harm grading assessment was performed.

Related sources S01 S02 S11 S12 S13 S14 S20 S21 S22 S23 S24 S25 S26 S27 S28

N41 · Has the original safety warning been kept from becoming personal treatment/discontinuation instructions?

Current findings: The original document explicitly states that it does not provide personal treatment/dosing instructions. For new tingling, burning, reduced sensation, or balance problems, it advises assessment of all products/other causes and preserves the original wording against unnecessary self-directed dose escalation or arbitrary discontinuation/replacement of prescribed treatment. This table creates no new clinical instructions.
Verification status: Met
Materials actually read: Summary reading: the specified original locations in the currently archived source summaries were actually read. Access to external material types was not attempted, and they were not read in this review.
Why unverified: Only the boundaries of the preserved information were verified; individual doses, discontinuation, or treatment were not assessed.
Reason for missing information: Individual causes/doses and treatment benefit–risk are not new conclusions of this table.
Required materials and conditions: Original safety warning and personal application/treatment boundary
Materials to obtain first: Original safety warning and personal application/treatment boundary
Further research: Compare the boundary between public informational statements and personal treatment instructions with the actual original values.
Remaining uncertainty: Individual causes/doses and treatment benefit–risk are not new conclusions of this table. This status concerns a narrow scope of record/material verification and does not newly assess clinical causality, occurrence probability, or individual safety.
Conditions for verification: Preserve the original safety information and assessment limitations, and do not newly assign individual recommended doses or instructions for self-directed dose escalation/prescription discontinuation.
Why this condition is needed: Needed to avoid turning harm information into instructions to stop/replace prescriptions or take individual doses.
Application exceptions: The blue record statuses in the review table and the original warning are not individual safety guarantees or self-treatment instructions.
Referenced methods: C01: M03 §3.1, §3.2.1–3.2.4 principles for clarifying the question; detailed separation rules are internally designed / H09: Chamgap's own interpretation boundaries. M19 principles are referenced; no formal causality tool was applied. Reason for application to this case: Needed to avoid turning harm information into instructions to stop/replace prescriptions or take individual doses. No formal causality/harm grading assessment was performed.

Related sources S11 S12 S13 S14