# Oral vitamin B6-only tablets (exact vitamer and salt unverified in the main trial) × Reduction of overall symptom severity in diagnosed PMS Verdict 3095 · Evidence Check Stored-material review date: 2026-10-05 Original evidence date: 2026-09-15 Review-criteria version: NGM-v3095-B6-MONOTHERAPY-PMS-GLOBAL-SEVERITY-1.0 Public page/material preparation date: 2026-11-01 Clinical papers were not read directly; existing review summaries were checked. No new clinical-literature search was performed. Unverified does not mean that research is absent or that there is no effect. ## Assessment scope - Population: Nonpregnant adults with PMS; main trial ages 18–45 with prospective symptom diaries; deficiency status and detailed differentiation from PMDD unverified - Ingredient, formulation and route: Vitamin B6 alone; vitamer and salt unverified in the main trial · Oral tablets; brand, crystal form, release form, and batch unverified · Oral - Dose: Daily total dose unverified: conflicting descriptions of tablet strength in the main trial; B6 dose not reported in the supportive trial - Comparator: Placebo; lactose and cellulose in the main trial; fixed common drug regimen unverified - Measured outcome: Main trial total score from a 12-symptom diary; registered outcome hierarchy and aggregation range unverified; lower is better - Duration: 2 diagnostic recording cycles followed by 2 treatment cycles; administration throughout the cycle - Questions outside this scope: PMDD, pregnancy nausea, individual emotional/anxiety symptoms, mastalgia, combination products, active comparators, and other scales/distinct studies are not combined as the same effect on the current overall score. OR, end-of-treatment difference, arithmetic change contrast, the carried-forward 80 mg record, and MCID are each kept distinct. ## Checklist items ### N01 · Which population, intervention, comparator, and endpoint define the distinct claim? Verification status: Met Reading scope: Summary reading: the specified original locations in the currently archived source summary were actually read. External originals and old separate copies were not read in this review. - Current findings: The original claim is “reduction of overall symptom severity in diagnosed PMS.” Oral B6-only tablets are compared with placebo in nonpregnant adults; PMDD, pregnancy nausea, and individual symptoms are not the direct claim. - Why unverified: The scope and identity conditions are met. This does not mean that symptom improvement or the efficacy of a particular dose has been established. - Reason for missing information: Dated records linking the original claim to the actual eligibility criteria, comparison, and endpoint - Required materials and conditions: Dated records linking the original claim to the actual eligibility criteria, comparison, and endpoint - Materials to obtain first: Dated records linking the original claim to the actual eligibility criteria, comparison, and endpoint - Further research: Compare the current manuscript with each trial's population, intervention, comparator, and endpoint, and record the reason for a change only if a boundary has changed. - Conditions for verification: The current /ko/effect is linked to the boundaries of nonpregnant PMS, oral B6 monotherapy, placebo, and overall symptom score. - Why this condition is needed: The current overall-symptom comparison must be separated from the historical claim that combined PMS and pregnancy nausea. - Application exceptions: Evidence for PMDD, individual emotional symptoms, mastalgia, or pregnancy nausea is not transferred to the current claim. - Remaining uncertainty: Dated records linking the original claim to the actual eligibility criteria, comparison, and endpoint: limited to the currently retained record, with no new assessment of clinical efficacy, individual probability of success, or safety. - Referenced methods: C01: question-clarification principles in M03 §3.1, §3.2.1–3.2.4; detailed separation rules are self-designed / C04: M03 §3.2.1; detailed population conditions are self-designed / C05: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are self-designed / C06: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are self-designed. Reason for applying these to this overall PMS score comparison: the current overall-symptom comparison must be separated from the historical claim that combined PMS and pregnancy nausea. No formal RoB2/GRADE assessment or clinical certification was performed. - Related sources: S02, S03 ### N02 · Are the prospectively confirmed PMS population, modern diagnostic assessment, and differentiation from PMDD verified? Verification status: Partly verified Reading scope: Summary reading: the specified original locations in the currently archived source summary were actually read. External originals and old separate copies were not read in this review. - Current findings: The main trial involved nonpregnant adults aged 18–45 and used prospective diaries over two diagnostic cycles. Deficiency status, detailed differentiation from PMDD, and modern diagnostic adjudication remain unverified. - Why unverified: The diaries and age range are preserved, but the detailed diagnosis and baseline status have not all been verified. - Reason for missing information: Inclusion and exclusion criteria, actual diagnostic diaries, and information on PMDD differentiation and baseline nutritional status - Required materials and conditions: Inclusion and exclusion criteria, actual diagnostic diaries, and information on PMDD differentiation and baseline nutritional status - Materials to obtain first: Inclusion and exclusion criteria, actual diagnostic diaries, and information on PMDD differentiation and baseline nutritional status - Further research: First compare the diagnostic procedures across trials, then examine comparative records for PMS populations confirmed using the same definition. - Conditions for verification: The diagnostic cycles, participant ages and selection, differentiation from PMDD, and baseline nutritional status are linked to actual records. - Why this condition is needed: Self-reported premenstrual symptoms and diagnosed PMS or PMDD cannot be treated as the same population. - Application exceptions: Unverified diagnostic details are not taken to mean that no PMS population exists or that treatment is ineffective for PMDD. - Remaining uncertainty: Inclusion and exclusion criteria, actual diagnostic diaries, and information on PMDD differentiation and baseline nutritional status: limited to the currently retained record, with no new assessment of clinical efficacy, individual probability of success, or safety. - Referenced methods: C04: M03 §3.2.1; detailed population conditions are self-designed / E08: M03 §3.2.1–3.2.4; details on dose, duration, and effect modification are self-designed. Reason for applying these to this overall PMS score comparison: self-reported premenstrual symptoms and diagnosed PMS or PMDD cannot be treated as the same population. No formal RoB2/GRADE assessment or clinical certification was performed. - Related sources: S02, S03 ### N03 · Is the main trial's B6-only arm distinguished from the Hypericum and placebo arms? Verification status: Met Reading scope: Summary reading: the specified original locations in the currently archived source summary were actually read. External originals and old separate copies were not read in this review. - Current findings: S03 has separate parallel arms for B6 alone, Hypericum, and placebo. The current comparison uses only B6 and placebo and does not add the effect of Hypericum. - Why unverified: The arm composition and attribution of the selected comparison are preserved. The conditions for verifying allocation concealment and dose have not thereby also been met. - Reason for missing information: Original records of each arm's intervention list, regimen, and comparator composition - Required materials and conditions: Original records of each arm's intervention list, regimen, and comparator composition - Materials to obtain first: Original records of each arm's intervention list, regimen, and comparator composition - Further research: Check the interventions table by arm and classify monotherapy, combination therapy, and comparisons with other ingredients separately. - Conditions for verification: The actual parallel-arm composition is distinguished from the B6-versus-placebo comparison to be used in this table. - Why this condition is needed: Reading the two ingredients in the paper's title as a combination regimen changes the attribution of the intervention's contribution. - Application exceptions: The use of Hypericum in another arm is not taken to imply concurrent administration in the B6-only arm. - Remaining uncertainty: Original records of each arm's intervention list, regimen, and comparator composition: limited to the currently retained record, with no new assessment of clinical efficacy, individual probability of success, or safety. - Referenced methods: C05: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are self-designed / E01: M08 §8.1–8.2.3; self-applied / E02: M03 §3.2.3, M08 §8.2.2–8.2.3; self-applied. Reason for applying these to this overall PMS score comparison: reading the two ingredients in the paper's title as a combination regimen changes the attribution of the intervention's contribution. No formal RoB2/GRADE assessment or clinical certification was performed. - Related sources: S03 ### N04 · Are the vitamer and salt of B6 in the key trials verified? Verification status: Unverified Reading scope: Summary reading: the specified original locations in the currently archived source summary were actually read. External originals and old separate copies were not read in this review. - Current findings: The exact vitamer and salt in the key trials remain unverified. The manuscript states that B6 is not the name of a single molecule and that pyridoxine, pyridoxal, and PLP were not treated as identical. - Why unverified: General ingredient descriptions do not establish the identity of the actual trial product. - Reason for missing information: Product ingredient lists, manufacturing specifications, and vitamer and salt records for the key trials - Required materials and conditions: Product ingredient lists, manufacturing specifications, and vitamer and salt records for the key trials - Materials to obtain first: Product ingredient lists, manufacturing specifications, and vitamer and salt records for the key trials - Further research: Cross-check the original trial's product identity records, and examine records for other vitamers as distinct exposures. - Conditions for verification: Verify the vitamer and salt of the product actually administered using trial-specific documents or manufacturing records. - Why this condition is needed: Pyridoxine, pyridoxal, PLP, and salts cannot be recast as chemically identical exposures. - Application exceptions: The trial's salt is not filled in from common commercial products or general NIH descriptions. - Remaining uncertainty: Product ingredient lists, manufacturing specifications, and vitamer and salt records for the key trials: limited to the currently retained record, with no new assessment of clinical efficacy, individual probability of success, or safety. - Referenced methods: C05: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are self-designed. Reason for applying this to this overall PMS score comparison: pyridoxine, pyridoxal, PLP, and salts cannot be recast as chemically identical exposures. No formal RoB2/GRADE assessment or clinical certification was performed. - Related sources: S02, S03, S15 ### N05 · Are details of the actual tablets, such as brand, origin, batch, and release form, verified? Verification status: Partly verified Reading scope: Summary reading: the specified original locations in the currently archived source summary were actually read. External originals and old separate copies were not read in this review. - Current findings: The route is oral and the formulation is a tablet. Manufacturing origin, brand, crystal form, release form, and batch remain unverified or inconsistently described. - Why unverified: Only the route and broad formulation have been verified; detailed product equivalence has not been established. - Reason for missing information: Manufacturing, product, batch, and release-form specifications for the administered tablets - Required materials and conditions: Manufacturing, product, batch, and release-form specifications for the administered tablets - Materials to obtain first: Manufacturing, product, batch, and release-form specifications for the administered tablets - Further research: Obtain trial-product documents to examine differences between formulations; do not substitute another commercial product. - Conditions for verification: Verify the oral route and actual product, batch, and release form, and distinguish the unverified dimensions. - Why this condition is needed: The fact that a product is an oral tablet alone does not establish equivalence in release, strength, or manufacturing conditions. - Application exceptions: Unverified origin or brand is not converted into a finding that another product lacks efficacy. - Remaining uncertainty: Manufacturing, product, batch, and release-form specifications for the administered tablets: limited to the currently retained record, with no new assessment of clinical efficacy, individual probability of success, or safety. - Referenced methods: C05: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are self-designed. Reason for applying this to this overall PMS score comparison: the fact that a product is an oral tablet alone does not establish equivalence in release, strength, or manufacturing conditions. No formal RoB2/GRADE assessment or clinical certification was performed. - Related sources: S02, S03 ### N06 · Are the main trial's tablet strength and total daily dose consistently verified? Verification status: Conflicting records Reading scope: Summary reading: the specified original locations in the currently archived source summary were actually read. External originals and old separate copies were not read in this review. - Current findings: The main trial's tablet-strength descriptions conflict, leaving the total daily dose unverified. The currently retained archived summary preserves the fact of the conflict, but does not contain the specific conflicting tablet-strength numbers or original statements. - Why unverified: Consistency of the actual daily dose remains unresolved. Successfully recording the conflict is distinguished from verifying the exposure. - Reason for missing information: Author confirmation of the conflicting original strength statements, dosing table, number of tablets per administration, frequency, and total daily dose - Required materials and conditions: Author confirmation of the conflicting original strength statements, dosing table, number of tablets per administration, frequency, and total daily dose - Materials to obtain first: Author confirmation of the conflicting original strength statements, dosing table, number of tablets per administration, frequency, and total daily dose - Further research: Compare the original dosing documents and revision history to verify a consistent exposure record, without calculating a new dose. - Conditions for verification: Tablet strength, number of tablets, frequency, total daily dose, and the basis for conversion are linked consistently. - Why this condition is needed: Conflicting descriptions of the study dose limit interpretation of the actual exposure and dose. - Application exceptions: Do not reconstruct numbers absent from the conflicting original statements or use the study dose as dosing instructions. - Remaining uncertainty: Author confirmation of the conflicting original strength statements, dosing table, number of tablets per administration, frequency, and total daily dose: limited to the currently retained record, with no new assessment of clinical efficacy, individual probability of success, or safety. - Referenced methods: C05: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are self-designed / E08: M03 §3.2.1–3.2.4; details on dose, duration, and effect modification are self-designed. Reason for applying these to this overall PMS score comparison: conflicting descriptions of the study dose limit interpretation of the actual exposure and dose. No formal RoB2/GRADE assessment or clinical certification was performed. - Related sources: S03 ### N07 · Is the supportive trial's daily B6 dose verified separately from the magnesium dose of 250 mg? Verification status: Not reported Reading scope: Summary reading: the specified original locations in the currently archived source summary were actually read. External originals and old separate copies were not read in this review. - Current findings: The retained S02 content explicitly states that the B6 dose could not be verified in the report. 250 mg refers to magnesium, not the daily dose in the B6-only arm. - Why unverified: The dose is described as not reported only within the supportive trial report content obtained at the time. This is not the result of a new check of the entire full text. - Reason for missing information: S02 records of the B6 dosing regimen and product, and the original dose statement - Required materials and conditions: S02 records of the B6 dosing regimen and product, and the original dose statement - Materials to obtain first: S02 records of the B6 dosing regimen and product, and the original dose statement - Further research: Compare the regimens by arm in S02 and extract the magnesium and B6 values separately. - Conditions for verification: In S02, verify the actual B6 amount at its original location, and keep it separate from the magnesium dose. - Why this condition is needed: Transferring the magnesium amount from another arm to the B6 dose misattributes the product and exposure. - Application exceptions: 250 mg is not relabeled as a B6 value. The absence of reporting is not generalized to the entire full text, which was not read in this review. - Remaining uncertainty: S02 records of the B6 dosing regimen and product, and the original dose statement: limited to the currently retained record, with no new assessment of clinical efficacy, individual probability of success, or safety. - Referenced methods: C05: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are self-designed / E02: M03 §3.2.3, M08 §8.2.2–8.2.3; self-applied. Reason for applying these to this overall PMS score comparison: transferring the magnesium amount from another arm to the B6 dose misattributes the product and exposure. No formal RoB2/GRADE assessment or clinical certification was performed. - Related sources: S02 ### N08 · Are the diagnostic and treatment cycles and information on actual administration and adherence verified? Verification status: Partly verified Reading scope: Summary reading: the specified original locations in the currently archived source summary were actually read. External originals and old separate copies were not read in this review. - Current findings: The main trial is preserved as 2 diagnostic recording cycles followed by 2 treatment cycles, with administration throughout the cycle. Actual adherence and arm-specific discontinuation and dosing changes remain unverified. - Why unverified: A nominal cycle schedule is available, but actual exposure received and adherence have not all been verified. - Reason for missing information: Cycle-specific records of administration, adherence, discontinuation, and rescue treatment - Required materials and conditions: Cycle-specific records of administration, adherence, discontinuation, and rescue treatment - Materials to obtain first: Cycle-specific records of administration, adherence, discontinuation, and rescue treatment - Further research: Compare the cycle schedule with actual administration records and examine deviations in relation to the actual effect of interest. - Conditions for verification: Verify the two diagnostic cycles, two treatment cycles, administration throughout the cycle, and actual adherence and discontinuation as distinct matters. - Why this condition is needed: Diagnostic records across menstrual cycles must be separated from treatment exposure and the period of adherence. - Application exceptions: The two cycles are not converted into a fixed number of days or an optimal treatment duration. - Remaining uncertainty: Cycle-specific records of administration, adherence, discontinuation, and rescue treatment: limited to the currently retained record, with no new assessment of clinical efficacy, individual probability of success, or safety. - Referenced methods: C05: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are self-designed / E02: M03 §3.2.3, M08 §8.2.2–8.2.3; self-applied / E08: M03 §3.2.1–3.2.4; details on dose, duration, and effect modification are self-designed. Reason for applying these to this overall PMS score comparison: diagnostic records across menstrual cycles must be separated from treatment exposure and the period of adherence. No formal RoB2/GRADE assessment or clinical certification was performed. - Related sources: S03 ### N09 · Is there direct evidence of sustained effects and long-term outcomes after treatment ends? Verification status: Unverified Reading scope: Summary reading: the specified original locations in the currently archived source summary were actually read. External originals and old separate copies were not read in this review. - Current findings: The current manuscript leaves sustained long-term effects unverified. It does not claim that effects persisting after discontinuation have been verified from the two-treatment-cycle comparison alone. - Why unverified: The currently archived material contains no direct estimate of sustained effects or follow-up information. - Reason for missing information: Follow-up schedules after treatment discontinuation and comparative outcomes on the same overall-symptom scale - Required materials and conditions: Follow-up schedules after treatment discontinuation and comparative outcomes on the same overall-symptom scale - Materials to obtain first: Follow-up schedules after treatment discontinuation and comparative outcomes on the same overall-symptom scale - Further research: Define sustained effects as a separate question and examine comparative follow-up records after discontinuation. - Conditions for verification: Follow-up time points, post-discontinuation outcomes, and sustained effects are linked through separate direct evidence. - Why this condition is needed: Needed to avoid extending a symptom comparison over two treatment cycles to a claim of sustained long-term effects. - Application exceptions: A long-term trial is not made mandatory for every study addressing the current narrow question of two cycles. - Remaining uncertainty: Follow-up schedules after treatment discontinuation and comparative outcomes on the same overall-symptom scale: limited to the currently retained record, with no new assessment of clinical efficacy, individual probability of success, or safety. - Referenced methods: E08: M03 §3.2.1–3.2.4; details on dose, duration, and effect modification are self-designed. Reason for applying this to this overall PMS score comparison: this is needed to avoid extending a symptom comparison over two treatment cycles to a claim of sustained long-term effects. No formal RoB2/GRADE assessment or clinical certification was performed. - Related sources: S02, S03 ### N10 · Is the actual comparison in terms of placebo, common drug regimens, and concomitant treatments verified? Verification status: Partly verified Reading scope: Summary reading: the specified original locations in the currently archived source summary were actually read. External originals and old separate copies were not read in this review. - Current findings: The main trial's placebo is preserved as lactose and cellulose. The fixed common drug regimen and arm-specific concomitant and rescue treatments remain unverified. - Why unverified: Placebo composition has been verified, but the influence of other treatments and equivalence of background treatment have not all been verified. - Reason for missing information: Placebo manufacturing records and arm-specific records of medicines, supplements, rescue treatment, and changes - Required materials and conditions: Placebo manufacturing records and arm-specific records of medicines, supplements, rescue treatment, and changes - Materials to obtain first: Placebo manufacturing records and arm-specific records of medicines, supplements, rescue treatment, and changes - Further research: Cross-check the actual comparator composition and background treatment to examine attribution of intervention differences. - Conditions for verification: Distinguish placebo composition and common treatment from arm-specific concomitant treatments and changes using actual records. - Why this condition is needed: Needed to avoid attributing differences in background treatment to an additional effect of B6 monotherapy. - Application exceptions: Do not assume that all changes in both arms are identical or fill an unverified field with an assertion of no concomitant treatment. - Remaining uncertainty: Placebo manufacturing records and arm-specific records of medicines, supplements, rescue treatment, and changes: limited to the currently retained record, with no new assessment of clinical efficacy, individual probability of success, or safety. - Referenced methods: C05: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are self-designed / E02: M03 §3.2.3, M08 §8.2.2–8.2.3; self-applied. Reason for applying these to this overall PMS score comparison: this is needed to avoid attributing differences in background treatment to an additional effect of B6 monotherapy. No formal RoB2/GRADE assessment or clinical certification was performed. - Related sources: S03 ### N11 · Are the allocation process, allocation concealment, and baseline balance verified? Verification status: Partly verified Reading scope: Summary reading: the specified original locations in the currently archived source summary were actually read. External originals and old separate copies were not read in this review. - Current findings: The main trial is preserved as a parallel-group design, and baseline total scores are also available. Unverified allocation concealment or registration was not asserted to be actual absence; detailed allocation and analysis flow remain unverified. - Why unverified: Some design and score information is available, but the sequence, concealment, and overall baseline balance could not all be verified. - Reason for missing information: Allocation sequence, concealment procedures, arm-specific baseline characteristics, and participant-flow records - Required materials and conditions: Allocation sequence, concealment procedures, arm-specific baseline characteristics, and participant-flow records - Materials to obtain first: Allocation sequence, concealment procedures, arm-specific baseline characteristics, and participant-flow records - Further research: Compare the original methods and allocation records with baseline characteristics relevant to the outcome, and record what was actually verified. - Conditions for verification: The random sequence, concealment, selection stages, and baseline balance relevant to the outcome are linked to their actual source locations. - Why this condition is needed: An RCT label alone does not establish that errors in the allocation process or confounding have been resolved. - Application exceptions: Do not assert that unverified allocation concealment was actually absent. - Remaining uncertainty: Allocation sequence, concealment procedures, baseline characteristics by group, and flow data; scope is limited to the currently preserved record, with no new determination of clinical efficacy, individual probability of success, or safety. - Referenced methods: E01: M08 §8.1–8.2.3; custom application. Reason for applying this to the PMS total-score comparison: an RCT label alone does not establish that allocation errors or confounding have been resolved. No formal RoB2/GRADE/clinical certification was performed. - Related sources: S03 ### N12 · Are blinding and collection procedures by group verified for the subjective diary assessment? Verification status: Unverified Reading scope: Summary reading: the specified original locations in the currently archived source summary were actually read. External originals and old separate copies were not read in this review. - Current findings: The currently archived material identifies a 12-symptom diary endpoint but does not contain specific details of how blinding was implemented or how diaries were collected by group. - Why unverified: Details of the measurement procedures cannot be verified within the summaries and structure currently saved. - Reason for missing information: Diary collection manual, blinding, assessment, and measurement schedules by group - Required materials and conditions: Diary collection manual, blinding, assessment, and measurement schedules by group - Materials to obtain first: Diary collection manual, blinding, assessment, and measurement schedules by group - Further research: Compare the methods section with the diary procedures and review the actual collection limitations for the subjective endpoint. - Conditions for verification: Verify the actual procedures for diary completion, collection timing, assessors, and blinding by group. - Why this condition is needed: For patient-reported endpoints, differences in expectations or collection procedures may be reflected in the total score. - Application exceptions: Do not use unverified blinding information to establish blinding failure or the magnitude of bias. - Remaining uncertainty: Diary collection manual, blinding, assessment, and measurement schedules by group; scope is limited to the currently preserved record, with no new determination of clinical efficacy, individual probability of success, or safety. - Referenced methods: E03: M08 Table 8.2.a, M03 §3.2.4; custom application. Reason for applying this to the PMS total-score comparison: for patient-reported endpoints, differences in expectations or collection procedures may be reflected in the total score. No formal RoB2/GRADE/clinical certification was performed. - Related sources: S03 ### N13 · Are the definition, direction, and aggregation range of the total 12-symptom diary score verified? Verification status: Partly verified Reading scope: Summary reading: the specified original locations in the currently archived source summary were actually read. External originals and old separate copies were not read in this review. - Current findings: The main trial uses the total score of a 12-symptom diary, with lower scores indicating better outcomes. Total-score normalization and aggregation range remain unverified, and the manuscript does not call the older scale DRSP. - Why unverified: The composition and direction are preserved, but a reproducible definition of the total-score calculation remains incomplete. - Reason for missing information: Original diary, scoring sheet, aggregation and normalization specifications, and scale validation materials - Required materials and conditions: Original diary, scoring sheet, aggregation and normalization specifications, and scale validation materials - Materials to obtain first: Original diary, scoring sheet, aggregation and normalization specifications, and scale validation materials - Further research: Compare the original score definitions and distinguish the total score from subdomains and other scales. - Conditions for verification: Verify the direction, composition, aggregation range, and scale name of the 12-symptom total score against the actual material. - Why this condition is needed: This is needed to avoid treating the study-specific total score as the modern DRSP or an individual emotional-symptom score. - Application exceptions: Do not call the older diary DRSP or transfer significance in a subdomain to the overall endpoint. - Remaining uncertainty: Original diary, scoring sheet, aggregation and normalization specifications, and scale validation materials; scope is limited to the currently preserved record, with no new determination of clinical efficacy, individual probability of success, or safety. - Referenced methods: C06: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptation is custom-designed / E03: M08 Table 8.2.a, M03 §3.2.4; custom application. Reason for applying this to the PMS total-score comparison: this is needed to avoid treating the study-specific total score as the modern DRSP or an individual emotional-symptom score. No formal RoB2/GRADE/clinical certification was performed. - Related sources: S03 ### N14 · Can the total-score calculation and normalization be verified reproducibly? Verification status: Unverified Reading scope: Summary reading: the specified original locations in the currently archived source summary were actually read. External originals and old separate copies were not read in this review. - Current findings: The original B2 rationale identifies a reporting and measurement problem: the explanation of total-score calculation and normalization is insufficiently reproducible. The currently archived summary does not contain the calculation formula. - Why unverified: The process used to generate the score cannot be reproduced within the currently preserved material. - Reason for missing information: Raw symptom scores, calculation formula, and rules for missing data and normalization - Required materials and conditions: Raw symptom scores, calculation formula, and rules for missing data and normalization - Materials to obtain first: Raw symptom scores, calculation formula, and rules for missing data and normalization - Further research: Compare the score-calculation documentation with the original table to review interpretability, without calculating a new score. - Conditions for verification: The calculation, missing-data handling, and normalization methods from individual symptom records through to the total score are verified. - Why this condition is needed: Even when means are available, interpretation of the measurement remains limited if the process used to generate the total score is unknown. - Application exceptions: Do not reassess the original historical B2 determination with a new score; distinguish verified reporting defects from unverified information. - Remaining uncertainty: Raw symptom scores, calculation formula, and rules for missing data and normalization; scope is limited to the currently preserved record, with no new determination of clinical efficacy, individual probability of success, or safety. - Referenced methods: E03: M08 Table 8.2.a, M03 §3.2.4; custom application / C06: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptation is custom-designed. Reason for applying this to the PMS total-score comparison: even when means are available, interpretation of the measurement remains limited if the process used to generate the total score is unknown. No formal RoB2/GRADE/clinical certification was performed. - Related sources: S03 ### N15 · Were the primary-endpoint hierarchy, timing, and analysis plan specified in advance? Verification status: Unverified Reading scope: Summary reading: the specified original locations in the currently archived source summary were actually read. External originals and old separate copies were not read in this review. - Current findings: The registered hierarchy of the main trial's total score remains unverified. S02 has the identifier IRCT201106216854N1, but registration details, history, and whether registration was prospective could not be verified. - Why unverified: The existence of an identifier alone cannot verify agreement between the prospective plan and the actual report. - Reason for missing information: Dated registration, protocol, and analysis plan, and the results table for the overall endpoint - Required materials and conditions: Dated registration, protocol, and analysis plan, and the results table for the overall endpoint - Materials to obtain first: Dated registration, protocol, and analysis plan, and the results table for the overall endpoint - Further research: Compare plan versions and dates with the actual overall endpoint and analysis, and record what remains unchecked. - Conditions for verification: The dates, total score, timing, and hierarchy in the registration, protocol, and analysis plan are compared with the actual report. - Why this condition is needed: The presence of a total score in the paper does not verify its registered hierarchy. - Application exceptions: Do not treat failure to obtain the registration as confirmation of nonregistration or selective reporting. - Remaining uncertainty: Dated registration, protocol, and analysis plan, and the results table for the overall endpoint; scope is limited to the currently preserved record, with no new determination of clinical efficacy, individual probability of success, or safety. - Referenced methods: E06: M08 Table 8.2.a, M04 §4.6.3; custom application. Reason for applying this to the PMS total-score comparison: the presence of a total score in the paper does not verify its registered hierarchy. No formal RoB2/GRADE/clinical certification was performed. - Related sources: S02, S03, S18 ### N16 · Can the flow of recruited, allocated, and analysed participants in the main trial be verified consistently? Verification status: Conflicting records Reading scope: Summary reading: the specified original locations in the currently archived source summary were actually read. External originals and old separate copies were not read in this review. - Current findings: The table analysis headers show B6 78 participants and placebo 78 participants. The manuscript states that internally inconsistent participant accounting across the abstract, methods, and tables makes a coherent analysis-population check difficult. Detailed recruitment and allocation counts are absent from the current summary. - Why unverified: The actual inconsistency in denominator flow remains unresolved, and the table denominators are not transferred to other stages. - Reason for missing information: Conflicting recruitment, allocation, completion, and analysis flow diagrams, and reasons for exclusion by group - Required materials and conditions: Conflicting recruitment, allocation, completion, and analysis flow diagrams, and reasons for exclusion by group - Materials to obtain first: Conflicting recruitment, allocation, completion, and analysis flow diagrams, and reasons for exclusion by group - Further research: Link each stage-specific and endpoint-specific denominator to its original location to check consistency only, without creating new participant totals. - Conditions for verification: Recruitment, allocation, completion, and analysis flow, and reasons for exclusion, are linked consistently across the abstract, methods, and tables. - Why this condition is needed: Using the table's 78 participants per group as overall recruitment or allocation counts changes which stage the denominator belongs to. - Application exceptions: Do not invent specific overall participant counts from the abstract, Methods, or tables that are absent from the currently archived summary. - Remaining uncertainty: Conflicting recruitment, allocation, completion, and analysis flow diagrams, and reasons for exclusion by group; scope is limited to the currently preserved record, with no new determination of clinical efficacy, individual probability of success, or safety. - Referenced methods: C07: M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptation is custom-designed / E01: M08 §8.1–8.2.3; custom application / E04: M08 §8.2.2, M15 §15.3.1; custom application. Reason for applying this to the PMS total-score comparison: using the table's 78 participants per group as overall recruitment or allocation counts changes which stage the denominator belongs to. No formal RoB2/GRADE/clinical certification was performed. - Related sources: S03 ### N17 · Do the baseline and end-of-treatment means, SDs, and denominators in the main trial table belong to the specified total score? Verification status: Met Reading scope: Summary reading: the specified original locations in the currently archived source summary were actually read. External originals and old separate copies were not read in this review. - Current findings: The preserved table shows B6 33.93(SD 6.95)→20.92(SD 5.26), placebo 33.86(SD 6.16)→23.90(SD 6.00), with analysis headers of 78 participants per group. All are study-specific total scores. - Why unverified: The types, endpoints, and table-denominator attribution of the currently preserved numbers have been verified. This does not mean that the original full text was newly checked or that allocation flow was resolved. - Reason for missing information: Original total-score table, definitions of dispersion for each value, and endpoint-specific analysis headers - Required materials and conditions: Original total-score table, definitions of dispersion for each value, and endpoint-specific analysis headers - Materials to obtain first: Original total-score table, definitions of dispersion for each value, and endpoint-specific analysis headers - Further research: Check the original locations of numbers, dispersion, and denominators, and preserve both the prior and revised values if corrections are made. - Conditions for verification: The four means, four SDs, analysis headers by group, and direction of the total score in the currently preserved original table are accurately linked. - Why this condition is needed: This is needed to preserve the original table's means, dispersion, and analysis headers without transferring them to other endpoints or stages. - Application exceptions: Do not change SD to SE or use the 78 participants per group as the overall allocation count. - Remaining uncertainty: Original total-score table, definitions of dispersion for each value, and endpoint-specific analysis headers; scope is limited to the currently preserved record, with no new determination of clinical efficacy, individual probability of success, or safety. - Referenced methods: C06: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptation is custom-designed / C07: M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptation is custom-designed / E04: M08 §8.2.2, M15 §15.3.1; custom application. Reason for applying this to the PMS total-score comparison: this is needed to preserve the original table's means, dispersion, and analysis headers without transferring them to other endpoints or stages. No formal RoB2/GRADE/clinical certification was performed. - Related sources: S03 ### N18 · Are the preserved arithmetic change contrast and end-of-treatment difference distinguished from the formal adjusted effect? Verification status: Met Reading scope: Summary reading: the specified original locations in the currently archived source summary were actually read. External originals and old separate copies were not read in this review. - Current findings: In the manuscript, -3.05 points is the historical arithmetic change contrast derived from reported means, and -2.98 points is the end-of-treatment difference. These are not a formal adjusted change contrast or its confidence interval, and they were not recalculated in this review. - Why unverified: The type of historical arithmetic and its boundary with the formal estimator have been verified. This does not mean that the conditions for causal effect or precision have been met. - Reason for missing information: Original calculation records C03·C04, the original table, and specifications for the formal change-contrast analysis - Required materials and conditions: Original calculation records C03·C04, the original table, and specifications for the formal change-contrast analysis - Materials to obtain first: Original calculation records C03·C04, the original table, and specifications for the formal change-contrast analysis - Further research: Perform only a traceability review comparing historical calculations with formal results, without producing new arithmetic values or CIs. - Conditions for verification: The original attribution of the -3.05-point change contrast and -2.98-point end-of-treatment difference is kept separate from the unverified formal estimator. - Why this condition is needed: This is needed to avoid treating the arithmetic contrast from reported means as the same estimator as a formal adjusted change contrast. - Application exceptions: Preserve the original historical values unchanged, without new calculations, imputation of correlations, or reconstruction of variances in this review. - Remaining uncertainty: Original calculation records C03·C04, the original table, and specifications for the formal change-contrast analysis; scope is limited to the currently preserved record, with no new determination of clinical efficacy, individual probability of success, or safety. - Referenced methods: C06: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptation is custom-designed / E04: M08 §8.2.2, M15 §15.3.1; custom application / E05: M15 §15.3.1–15.3.3; custom application. Reason for applying this to the PMS total-score comparison: this is needed to avoid treating the arithmetic contrast from reported means as the same estimator as a formal adjusted change contrast. No formal RoB2/GRADE/clinical certification was performed. - Related sources: S03 ### N19 · Are the formal between-group change contrast, adjustment method, and confidence interval verified? Verification status: Unverified Reading scope: Summary reading: the specified original locations in the currently archived source summary were actually read. External originals and old separate copies were not read in this review. - Current findings: Formal change-contrast confidence intervals remain unverified for the main and supportive trials. The manuscript retains the limitations that ANCOVA was not reported and correlations or variances were not estimated. - Why unverified: The formal change-contrast analysis and its interval cannot be verified within the currently preserved material. - Reason for missing information: Original change-contrast analysis results, model, analysis population, variance, and CI - Required materials and conditions: Original change-contrast analysis results, model, analysis population, variance, and CI - Materials to obtain first: Original change-contrast analysis results, model, analysis population, variance, and CI - Further research: Compare the original results and analysis plan to verify the reported interval for the same estimator, without calculating a new interval. - Conditions for verification: Verify the analysis population, adjustment, variance, CI, and actual timing of the between-group change contrast. - Why this condition is needed: A point estimate or end-of-treatment SD alone cannot establish the precision of the effect on change scores. - Application exceptions: Do not impute unverified correlations or variances, or treat an end-of-treatment interval as a change-contrast CI. - Remaining uncertainty: Original change-contrast analysis results, model, analysis population, variance, and CI; scope is limited to the currently preserved record, with no new determination of clinical efficacy, individual probability of success, or safety. - Referenced methods: E04: M08 §8.2.2, M15 §15.3.1; custom application / E05: M15 §15.3.1–15.3.3; custom application. Reason for applying this to the PMS total-score comparison: a point estimate or end-of-treatment SD alone cannot establish the precision of the effect on change scores. No formal RoB2/GRADE/clinical certification was performed. - Related sources: S02, S03 ### N20 · Is the B6-placebo between-group test of change verified separately from within-group tests and the overall three-group test? Verification status: Unverified Reading scope: Summary reading: the specified original locations in the currently archived source summary were actually read. External originals and old separate copies were not read in this review. - Current findings: The manuscript states that within-group significance or the overall three-group test result was not substituted for the exact B6-placebo test of the change contrast. The currently archived summary does not contain the specific P value of that original test. - Why unverified: The limitations on test attribution have been preserved, but the exact test of change between the two groups and the handling of multiplicity remain unverified. - Reason for missing information: Original tests, post hoc contrasts, handling of multiplicity, and analysis plan - Required materials and conditions: Original tests, post hoc contrasts, handling of multiplicity, and analysis plan - Materials to obtain first: Original tests, post hoc contrasts, handling of multiplicity, and analysis plan - Further research: Identify the comparisons in the original test table and review within-group tests, the overall test, and the test of the two selected groups separately. - Conditions for verification: The test of the change contrast, contrasts, and handling of multiplicity for the two selected groups are verified at their actual source locations. - Why this condition is needed: Within-group significance and the overall three-group test are not a test of the change contrast between the two selected groups. - Application exceptions: Do not reconstruct original P values or post hoc test values absent from the preserved archived summary, or treat nonsignificance as an effect of 0. - Remaining uncertainty: Original tests, post hoc contrasts, handling of multiplicity, and analysis plan; scope is limited to the currently preserved record, with no new determination of clinical efficacy, individual probability of success, or safety. - Referenced methods: E04: M08 §8.2.2, M15 §15.3.1; custom application / E06: M08 Table 8.2.a, M04 §4.6.3; custom application. Reason for applying this to the PMS total-score comparison: within-group significance and the overall three-group test are not a test of the change contrast between the two selected groups. No formal RoB2/GRADE/clinical certification was performed. - Related sources: S03 ### N21 · Are the analysis population, missing data, attrition, and definition of the effect of interest verified? Verification status: Unverified Reading scope: Summary reading: the specified original locations in the currently archived source summary were actually read. External originals and old separate copies were not read in this review. - Current findings: Detailed allocation and analysis flow remain unverified, and the main trial's table headers conflict with the overall participant-count description. In the supportive trial, completion counts and endpoint-specific analysis denominators may differ, so they are kept separate. - Why unverified: Direct specifications of the effect of interest and missing-data handling could not be verified in the current summary. - Reason for missing information: Endpoint-specific analysis populations, missing data, reasons for attrition, and ITT/PP and adjustment specifications - Required materials and conditions: Endpoint-specific analysis populations, missing data, reasons for attrition, and ITT/PP and adjustment specifications - Materials to obtain first: Endpoint-specific analysis populations, missing data, reasons for attrition, and ITT/PP and adjustment specifications - Further research: Compare the analysis plan and flow diagram with the result denominators to distinguish the effect being estimated. - Conditions for verification: Allocation, completion, and analysis by group are linked to missing-data handling and the effect of interest. - Why this condition is needed: This is needed to avoid treating an analysis of completers as an effect of assignment or as ITT. - Application exceptions: Do not label an unknown analysis as ITT or PP, or treat missing data as 0. - Remaining uncertainty: Endpoint-specific analysis populations, missing data, reasons for attrition, and ITT/PP and adjustment specifications; scope is limited to the currently preserved record, with no new determination of clinical efficacy, individual probability of success, or safety. - Referenced methods: C07: M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptation is custom-designed / E02: M03 §3.2.3, M08 §8.2.2–8.2.3; custom application / E04: M08 §8.2.2, M15 §15.3.1; custom application. Reason for applying this to the PMS total-score comparison: this is needed to avoid treating an analysis of completers as an effect of assignment or as ITT. No formal RoB2/GRADE/clinical certification was performed. - Related sources: S02, S03 ### N22 · Are the supportive trial's allocation, completion, and endpoint denominators and its 30-symptom results distinguished? Verification status: Partly verified Reading scope: Summary reading: the specified original locations in the currently archived source summary were actually read. External originals and old separate copies were not read in this review. - Current findings: S02 allocated 42 participants per group; completers were B6 36 and placebo 37. The 30-symptom diary values B6 36.51→22.84 and placebo 35.80→28.41, and the historical arithmetic contrast of -6.28 points, are preserved, but endpoint-specific analysis denominators and the between-group change CI remain unverified. - Why unverified: Allocation and completion counts and scores are available, but endpoint denominators, variance, and formal intervals could not be established. - Reason for missing information: S02 endpoint-specific analysis headers, score tables, variance, missing data, and change-contrast results - Required materials and conditions: S02 endpoint-specific analysis headers, score tables, variance, missing data, and change-contrast results - Materials to obtain first: S02 endpoint-specific analysis headers, score tables, variance, missing data, and change-contrast results - Further research: Compare the original tables with allocation, completion, and analysis kept as separate stages, without recalculating the currently preserved historical arithmetic. - Conditions for verification: Verify separately the original attribution of S02 allocation, completion, and endpoint analysis denominators and the 30-symptom score. - Why this condition is needed: Treating 42 allocated participants, 36/37 completers, and endpoint analysis counts as the same denominator changes the attribution of results. - Application exceptions: Do not establish completion counts as endpoint denominators or combine arithmetic contrasts from different scales. - Remaining uncertainty: S02 endpoint-specific analysis headers, score tables, variance, missing data, and change-contrast results; scope is limited to the currently preserved record, with no new determination of clinical efficacy, individual probability of success, or safety. - Referenced methods: C06: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptation is custom-designed / C07: M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptation is custom-designed / E04: M08 §8.2.2, M15 §15.3.1; custom application. Reason for applying this to the PMS total-score comparison: treating 42 allocated participants, 36/37 completers, and endpoint analysis counts as the same denominator changes the attribution of results. No formal RoB2/GRADE/clinical certification was performed. - Related sources: S02 ### N23 · Is there evidence supporting conversion of the 12-symptom and 30-symptom scales for comparison in the same effect units? Verification status: Unverified Reading scope: Summary reading: the specified original locations in the currently archived source summary were actually read. External originals and old separate copies were not read in this review. - Current findings: The main trial uses a 12-symptom diary, and the supportive trial uses a separate 30-symptom diary. The manuscript does not combine -3.05 points and -6.28 points and provides no evidence supporting conversion to a common scale. - Why unverified: The fact that the scales differ has been verified, but comparability in the same clinical units remains unverified. - Reason for missing information: The two original scales, score ranges, validation, and evidence for the validity of conversion - Required materials and conditions: The two original scales, score ranges, validation, and evidence for the validity of conversion - Materials to obtain first: The two original scales, score ranges, validation, and evidence for the validity of conversion - Further research: Compare results separately by scale, and do not combine them into a common effect without validated evidence supporting conversion. - Conditions for verification: Verify the composition, ranges, and validation of the two scales, and justified conversion to a common unit of interpretation. - Why this condition is needed: Comparing numerical differences in different total scores as the same amount of improvement erases the differences between scales. - Application exceptions: Do not newly calculate a common scale, pooled result, or standardized effect. - Remaining uncertainty: Materials on the two original scales, score ranges, validation, and validity of conversion. Scope is limited to the currently retained records; no new judgment is made about clinical efficacy, an individual's probability of success, or safety. - Referenced methods: C06: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptation is custom-designed / E03: M08 Table 8.2.a, M03 §3.2.4; custom application / E07: M04 §4.6.1–4.6.2, M15 §15.3.1; custom application. Reason for applying this to the PMS total-score comparison: comparing numerical differences in different total scores as the same amount of improvement erases the differences between scales. No formal RoB2/GRADE/clinical certification was performed. - Related sources: S02, S03 ### N24 · Have the original Results location, scale, denominators, and dispersion for the carried-forward 80 mg/day values been recovered? Verification status: Partly verified Reading scope: Summary reading: the specified original locations in the currently archived source summary were actually read. External originals and old separate copies were not read in this review. - Current findings: S06 preserves 80 mg/day, B6 -1.80 and placebo -0.93, an initial sample of 160 with 94 analysed, and the historical arithmetic change contrast of -0.87 points. The exact original Results location, scale, dispersion, and denominators by stage and arm remain unrecovered; these values were not used for grading or independent replication. - Why unverified: The carried-forward values and their limitations were preserved, but direct traceability to the original results and the analysis details could not be verified. - Reason for missing information: The original Results location, scale, denominators by arm and stage, and dispersion for S06, together with the original C10 calculation record - Required materials and conditions: The original Results location, scale, denominators by arm and stage, and dispersion for S06, together with the original C10 calculation record - Materials to obtain first: The original Results location, scale, denominators by arm and stage, and dispersion for S06, together with the original C10 calculation record - Further research: First review the provenance of the existing numbers, and do not integrate them quantitatively before their identity and scope are recovered. - Conditions for verification: The exact original Results location, scale, denominators by stage and arm, and dispersion are linked to the carried-forward values. - Why this condition is needed: This is needed to avoid upgrading numbers retained in the resumption request to newly verified original results or independent replication. - Application exceptions: Do not relabel 160 as the randomized count or 94 as a per-arm count, or invent an SD, CI, or P for -0.87 points. - Remaining uncertainty: The original Results location, scale, denominators by arm and stage, and dispersion for S06, together with the original C10 calculation record. Scope is limited to the currently retained records; no new judgment is made about clinical efficacy, an individual's probability of success, or safety. - Referenced methods: C03: data collection/selection principles in M04 §4.5–4.6; separation of access from reading and the hyperlink contract are custom designs / C06: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are custom designs / C07: M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptations are custom designs / E05: M15 §15.3.1–15.3.3; custom application. Reason for applying this to the overall PMS score comparison: this is needed to avoid upgrading numbers retained in the resumption request to newly verified original results or independent replication. No formal RoB2/GRADE assessment or clinical certification was performed. - Related sources: S06 ### N25 · Is the 2020 correction distinguished as an authorship change, an efficacy-number correction, or a retraction? Verification status: Met Reading scope: Summary reading: the specified original locations in the currently archived source summary were actually read. External originals and old separate copies were not read in this review. - Current findings: S07 is a 2020 correction adding the omitted author Shahnaz Babayanzad Ahari. It was not described as an efficacy-number correction or a retraction, and it belongs to the same trial publication family as S06. - Why unverified: The correction type and trial relationship were distinguished in the retained record. The external full correction text has not been newly read in this review. - Reason for missing information: The changes and author list in the correction document, and its link to the original article - Required materials and conditions: The changes and author list in the correction document, and its link to the original article - Materials to obtain first: The changes and author list in the correction document, and its link to the original article - Further research: Compare only the items changed by correction or retraction documents; review changes to the original numbers only when separately verified. - Conditions for verification: The actual type of correction event and its link to the original trial are stated explicitly. - Why this condition is needed: This is needed to avoid interpreting a correction adding an author as a correction to result numbers or a retraction. - Application exceptions: Do not reassess the study effect or independence score solely because of an authorship change. - Remaining uncertainty: The changes and author list in the correction document, and its link to the original article. Scope is limited to the currently retained records; no new judgment is made about clinical efficacy, an individual's probability of success, or safety. - Referenced methods: C08: M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses is a custom design / C09: M04 §4.5, §4.6.3; limits on transitioning to current materials are based on the user's scope and custom design / E06: M08 Table 8.2.a, M04 §4.6.3; custom application. Reason for applying this to the overall PMS score comparison: this is needed to avoid interpreting a correction adding an author as a correction to result numbers or a retraction. No formal RoB2/GRADE assessment or clinical certification was performed. - Related sources: S06, S07 ### N26 · Do the 1999 review's 9 trials and 940 participants all represent the same eligible comparison? Verification status: Partly verified Reading scope: Summary reading: the specified original locations in the currently archived source summary were actually read. External originals and old separate copies were not read in this review. - Current findings: The review's 9 trials and 940 participants include multivitamin trials and trials assessing mastalgia alone. They do not all represent the same comparison of overall PMS symptoms with B6 monotherapy, and they are not added up as independent studies in the current table. - Why unverified: The heterogeneous inclusion scope was identified, but detailed eligibility and cohort relationships could not be established for every trial. - Reason for missing information: S01's included-trial table, interventions, populations, endpoints, and links to original reports - Required materials and conditions: S01's included-trial table, interventions, populations, endpoints, and links to original reports - Materials to obtain first: S01's included-trial table, interventions, populations, endpoints, and links to original reports - Further research: Compare the included trials against each question, and do not use review totals as the number of study families or the denominator for the current effect. - Conditions for verification: Verify each included trial's ingredients, population, comparator, endpoints, and whether it shares a cohort with another trial report. - Why this condition is needed: This is needed to avoid counting the review totals as independent repetitions of the same B6-only PMS trial comparison. - Application exceptions: Do not automatically remove multivitamin or mastalgia-only trials and then calculate a new eligible count. - Remaining uncertainty: S01's included-trial table, interventions, populations, endpoints, and links to original reports. Scope is limited to the currently retained records; no new judgment is made about clinical efficacy, an individual's probability of success, or safety. - Referenced methods: C02: the distinction between studies and reports in M04 §4.6.1–4.6.2; cohort/outcome linkage is a custom application / C04: M03 §3.2.1; detailed population conditions are custom designs / C05: M03 §3.2.2–3.2.3; reverse-direction flagging and test adaptations are custom designs / E07: M04 §4.6.1–4.6.2, M15 §15.3.1; custom application. Reason for applying this to the overall PMS score comparison: this is needed to avoid counting the review totals as independent repetitions of the same B6-only PMS trial comparison. No formal RoB2/GRADE assessment or clinical certification was performed. - Related sources: S01 ### N27 · Can the definition, denominator, and comparator represented by the review's improvement OR 2.15 be verified? Verification status: Partly verified Reading scope: Summary reading: the specified original locations in the currently archived source summary were actually read. External originals and old separate copies were not read in this review. - Current findings: For the B6-only subgroup, an improvement OR of 2.15 (CI 1.79–2.59) is retained. It is not a percentage reduction in the overall symptom score or an individual's probability of improvement. The currently archived summary does not contain a table of improvement classifications or subgroup events and denominators. - Why unverified: The measure, subgroup, and interval are available, but traceability of the specific improvement definition and event denominators remains incomplete. - Reason for missing information: S01's definition of improvement, events in the monotherapy subgroup, comparator, denominators, and original OR table - Required materials and conditions: S01's definition of improvement, events in the monotherapy subgroup, comparator, denominators, and original OR table - Materials to obtain first: S01's definition of improvement, events in the monotherapy subgroup, comparator, denominators, and original OR table - Further research: Link the review's categorical results to the original table and review them separately from score results, without recalculating effects. - Conditions for verification: Link the improvement definition, monotherapy subgroup, denominators, effect direction, and CI to the original material. - Why this condition is needed: This is needed to avoid reading an odds ratio for improvement as a percentage reduction in the total score or an individual's probability of success. - Application exceptions: Do not convert the OR to an RR, score change, or probability, or recalculate it. - Remaining uncertainty: S01's definition of improvement, events in the monotherapy subgroup, comparator, denominators, and original OR table. Scope is limited to the currently retained records; no new judgment is made about clinical efficacy, an individual's probability of success, or safety. - Referenced methods: C06: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are custom designs / C07: M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptations are custom designs / E04: M08 §8.2.2, M15 §15.3.1; custom application / E05: M15 §15.3.1–15.3.3; custom application. Reason for applying this to the overall PMS score comparison: this is needed to avoid reading an odds ratio for improvement as a percentage reduction in the total score or an individual's probability of success. No formal RoB2/GRADE assessment or clinical certification was performed. - Related sources: S01 ### N28 · Are reports from the same trial, protocols, and possible cohort overlaps identified? Verification status: Partly verified Reading scope: Summary reading: the specified original locations in the currently archived source summary were actually read. External originals and old separate copies were not read in this review. - Current findings: S11 is grouped as an earlier partial report of S03, and S21 as the protocol for S08. Possible cohort overlap between S19 and S02 remains unverified, and it is not counted as independent replication of B6 monotherapy. - Why unverified: The two family links are present, but the actual cohort relationship of S19/S02 and the total unique participant count remain unverified. - Reason for missing information: A linkage table covering trial registration, sites, recruitment dates, participants, and reports, together with overlap materials - Required materials and conditions: A linkage table covering trial registration, sites, recruitment dates, participants, and reports, together with overlap materials - Materials to obtain first: A linkage table covering trial registration, sites, recruitment dates, participants, and reports, together with overlap materials - Further research: Link reports to trial families, distinguish confirmed, possible, and unknown relationships, and leave unverified unique participant counts blank. - Conditions for verification: Link the established relationships of S03/S11 and S08/S21 and the unverified relationship of S19/S02 to their respective original locations. - Why this condition is needed: This is needed to avoid double-counting reports or protocols as independent trials. - Application exceptions: Do not turn unverified overlap into confirmed independence or a confirmed shared cohort. - Remaining uncertainty: A linkage table covering trial registration, sites, recruitment dates, participants, and reports, together with overlap materials. Scope is limited to the currently retained records; no new judgment is made about clinical efficacy, an individual's probability of success, or safety. - Referenced methods: C02: the distinction between studies and reports in M04 §4.6.1–4.6.2; cohort/outcome linkage is a custom application / E07: M04 §4.6.1–4.6.2, M15 §15.3.1; custom application. Reason for applying this to the overall PMS score comparison: this is needed to avoid double-counting reports or protocols as independent trials. No formal RoB2/GRADE assessment or clinical certification was performed. - Related sources: S02, S03, S08, S11, S19, S21 ### N29 · Are the boundaries between overall results that are not favorable, emotional-domain results, and other interventions identified? Verification status: Partly verified Reading scope: Summary reading: the specified original locations in the currently archived source summary were actually read. External originals and old separate copies were not read in this review. - Current findings: Doll's emotional-domain signal is not transferred to overall improvement. Kendall's original overall mean and CI remain unverified. S08 involves an active comparator and inclusion of riboflavin; S09 concerns anxiety with a combination; S19 is a combination study; and S20 has no B6 arm. These are kept separate from the direct overall effect. - Why unverified: Contrary and scope-limited materials were retained, but the complete original overall results and detailed comparisons in older studies have not all been verified. - Reason for missing information: Overall and domain-specific outcome tables for each trial, with ingredients, comparators, and endpoint-specific denominators - Required materials and conditions: Overall and domain-specific outcome tables for each trial, with ingredients, comparators, and endpoint-specific denominators - Materials to obtain first: Overall and domain-specific outcome tables for each trial, with ingredients, comparators, and endpoint-specific denominators - Further research: Compare favorable, no-difference, and unfavorable results as materials addressing the same question, while separating results for other endpoints or interventions. - Conditions for verification: The limited findings of Doll and Kendall and the roles of active comparators, combinations, and other interventions are distinguished from overall results. - Why this condition is needed: This is needed to avoid retaining only some favorable results or extrapolating emotional or anxiety domain results to overall PMS success. - Application exceptions: Do not convert nonsignificance or unverified overall results into an effect of 0 or equivalence. - Remaining uncertainty: Overall and domain-specific outcome tables for each trial, with ingredients, comparators, and endpoint-specific denominators. Scope is limited to the currently retained records; no new judgment is made about clinical efficacy, an individual's probability of success, or safety. - Referenced methods: C08: M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses is a custom design / E07: M04 §4.6.1–4.6.2, M15 §15.3.1; custom application / E09: M03 §3.2.4; custom limits on extrapolation. Reason for applying this to the overall PMS score comparison: this is needed to avoid retaining only some favorable results or extrapolating emotional or anxiety domain results to overall PMS success. No formal RoB2/GRADE assessment or clinical certification was performed. - Related sources: S04, S05, S08, S09, S19, S20 ### N30 · Are research funding, product supply, and conflict-of-interest declarations verified separately from independent funding? Verification status: Partly verified Reading scope: Summary reading: the specified original locations in the currently archived source summary were actually read. External originals and old separate copies were not read in this review. - Current findings: S03 distinguishes the authors' declaration of no COI from the unverified specific funding and B6 supplier. In S02, supply of coded tablets by the university pharmacy was verified, but funding and author COI remain unverified. Other trials likewise retain their unresolved details within the available material scope. - Why unverified: Some supply and declaration details are available, but independent funding and all supply and employment relationships could not be established. - Reason for missing information: Trial-specific funding, product-supply agreements, author employment, patents, and COI declarations - Required materials and conditions: Trial-specific funding, product-supply agreements, author employment, patents, and COI declarations - Materials to obtain first: Trial-specific funding, product-supply agreements, author employment, patents, and COI declarations - Further research: Compare declarations separately with actual funding and supply materials, and record the limits on interpreting independence. - Conditions for verification: For each trial, link the respective verified scope and unresolved details of funding, supply, and COI. - Why this condition is needed: A declaration of no conflicts of interest or pharmacy supply does not prove independent funding or independent replication. - Application exceptions: Do not turn unverified interests into confirmed independence or automatic exclusion. - Remaining uncertainty: Trial-specific funding, product-supply agreements, author employment, patents, and COI declarations. Scope is limited to the currently retained records; no new judgment is made about clinical efficacy, an individual's probability of success, or safety. - Referenced methods: C10: Chamgap's own independence and attribution conditions. The formal methods sections used in this pilot do not warrant all of these detailed items. Reason for applying this to the overall PMS score comparison: a declaration of no conflicts of interest or pharmacy supply does not prove independent funding or independent replication. No formal RoB2/GRADE assessment or clinical certification was performed. - Related sources: S02, S03, S04, S05, S06 ### N31 · Are adverse-event collection, denominators, and follow-up verified for the same PMS population and exposure? Verification status: Unverified Reading scope: Summary reading: the specified original locations in the currently archived source summary were actually read. External originals and old separate copies were not read in this review. - Current findings: The original safety explanation states that the absence of reports of serious adverse events in short trials does not establish long-term neurological safety. The currently retained archived summary does not contain complete AE collection tables, denominators, or discontinuation results for each PMS comparison. - Why unverified: A complete harm comparison for the same population, actual dose, and duration could not be verified. - Reason for missing information: Trial-specific AE definitions, collection, exposure denominators by arm, duration, and discontinuation materials - Required materials and conditions: Trial-specific AE definitions, collection, exposure denominators by arm, duration, and discontinuation materials - Materials to obtain first: Trial-specific AE definitions, collection, exposure denominators by arm, duration, and discontinuation materials - Further research: Compare efficacy and harm outcomes separately, and review follow-up and collection methods suited to neurological outcomes. - Conditions for verification: Trial-specific AE definitions, systematic collection, exposure denominators, duration, and discontinuations are verified. - Why this condition is needed: This is needed to avoid reading the absence of reported serious adverse events in a short trial as long-term safety. - Application exceptions: Do not delete efficacy materials or fill unreported harm counts or risks with 0. - Remaining uncertainty: Trial-specific AE definitions, collection, exposure denominators by arm, duration, and discontinuation materials. Scope is limited to the currently retained records; no new judgment is made about clinical efficacy, an individual's probability of success, or safety. - Referenced methods: E10: M19 §19.1.2–19.2.4; custom application / H01: M19 §19.1.2–19.2.4; detailed distinctions are custom designs / H04: M19 §19.1.2–19.2.4; custom application / H06: M19 §19.1.2–19.2.4, M04 §4.6.3; custom application. Reason for applying this to the overall PMS score comparison: this is needed to avoid reading the absence of reported serious adverse events in a short trial as long-term safety. No formal RoB2/GRADE assessment or clinical certification was performed. - Related sources: S02, S03, S12, S13, S14, S16 ### N32 · Are general B6 neuropathy warnings distinguished from risk estimates in PMS trials? Verification status: Partly verified Reading scope: Summary reading: the specified original locations in the currently archived source summary were actually read. External originals and old separate copies were not read in this review. - Current findings: The retained TGA account records neuropathy reports even below 50 mg/day and warns about cumulative intake and potentially irreversible injury. This does not newly establish the incidence in PMS trials or comparative risk by specific vitamer or product. - Why unverified: General safety context is available, but there is no exposure, denominator, and risk comparison matching the PMS trials. - Reason for missing information: Products, combined exposure, populations, duration, and denominators in neuropathy materials, together with PMS safety follow-up - Required materials and conditions: Products, combined exposure, populations, duration, and denominators in neuropathy materials, together with PMS safety follow-up - Materials to obtain first: Products, combined exposure, populations, duration, and denominators in neuropathy materials, together with PMS safety follow-up - Further research: Review general regulatory and safety-signal materials separately from direct comparative harm materials, and do not calculate new thresholds or risks. - Conditions for verification: Separate the population, cumulative exposure, and scope of general warnings from the unverified direct PMS harm evidence. - Why this condition is needed: It has not been verified that official general safety information concerns the same exposure and population as the PMS trials, including their actual doses and durations. - Application exceptions: Do not turn reports below 50 mg/day into a threshold below which no harm occurs or a risk estimate covering all low doses. - Remaining uncertainty: Products, combined exposure, populations, duration, and denominators in neuropathy materials, together with PMS safety follow-up. Scope is limited to the currently retained records; no new judgment is made about clinical efficacy, an individual's probability of success, or safety. - Referenced methods: E10: M19 §19.1.2–19.2.4; custom application / H04: M19 §19.1.2–19.2.4; custom application / H08: M19 §19.1.2–19.2.4; custom application / H09: Chamgap's own interpretation boundary. M19 principles are referenced; no formal causality tool is applied. Reason for applying this to the overall PMS score comparison: it has not been verified that official general safety information concerns the same exposure and population as the PMS trials, including their actual doses and durations. No formal RoB2/GRADE assessment or clinical certification was performed. - Related sources: S12, S13, S14, S16 ### N33 · Are the EFSA upper limit and Australia's future regulation distinguished from treatment doses and current regulations? Verification status: Met Reading scope: Summary reading: the specified original locations in the currently archived source summary were actually read. External originals and old separate copies were not read in this review. - Current findings: The original cutoff is 2026-09-15. EFSA's adult 12 mg/day is an upper limit for chronic total intake; TGA's pharmacist-only change for above 50 mg~up to 200 mg/day is retained as scheduled to take effect on 2027-06-01. These are not treatment doses or current evidence of efficacy. - Why unverified: Only the meaning and date boundaries of the retained regulatory and safety record were checked. This status does not newly certify current law or individual safety. - Reason for missing information: The edition, publication/effective dates, and scope of the official documents, together with the original cutoff date - Required materials and conditions: The edition, publication/effective dates, and scope of the official documents, together with the original cutoff date - Materials to obtain first: The edition, publication/effective dates, and scope of the official documents, together with the original cutoff date - Further research: Within an authorized update scope, compare document editions and effective dates, and keep them separate from treatment doses and biological thresholds. - Conditions for verification: The nature of 12 mg/day as an upper limit for total intake and the time boundary of the scheduled effective date, 2027-06-01, are kept distinct. - Why this condition is needed: The upper limit for total nutrient intake and the effective date of sales rules are different facts from PMS treatment efficacy or a threshold below which no harm occurs. - Application exceptions: Present this as the record at the original cutoff, without performing a current-law lookup or creating a dose recommendation in this review. - Remaining uncertainty: The edition, publication/effective dates, and scope of the official documents, together with the original cutoff date. Scope is limited to the currently retained records; no new judgment is made about clinical efficacy, an individual's probability of success, or safety. - Referenced methods: C05: M03 §3.2.2–3.2.3; reverse-direction flagging and test adaptations are custom designs / C09: M04 §4.5, §4.6.3; limits on transitioning to current materials are based on the user's scope and custom design / E10: M19 §19.1.2–19.2.4; custom application / H09: Chamgap's own interpretation boundary. M19 principles are referenced; no formal causality tool is applied. Reason for applying this to the overall PMS score comparison: the upper limit for total nutrient intake and the effective date of sales rules are different facts from PMS treatment efficacy or a threshold below which no harm occurs. No formal RoB2/GRADE assessment or clinical certification was performed. - Related sources: S12, S14 ### N34 · Are statistical magnitude, clinical importance, and other clinical questions kept separate? Verification status: Unverified Reading scope: Summary reading: the specified original locations in the currently archived source summary were actually read. External originals and old separate copies were not read in this review. - Current findings: The historical end-of-treatment Hedges g=-0.53 is a statistical-magnitude classification under the original scoring rubric, not a validated between-group MCID. Clinical importance and sustained benefit remain unverified, and this is not a verdict on PMDD or pregnancy nausea. - Why unverified: The statistical value was preserved, but there is no validated clinical-importance criterion for this scale or direct evidence for events or other populations. - Reason for missing information: Materials on a validated MCID, importance to patients, and applicability for the overall scale in question - Required materials and conditions: Materials on a validated MCID, importance to patients, and applicability for the overall scale in question - Materials to obtain first: Materials on a validated MCID, importance to patients, and applicability for the overall scale in question - Further research: Compare evidence on importance to patients and scale validation against the results, without inventing arbitrary thresholds or success probabilities. - Conditions for verification: Verified clinical importance and applicability for the overall PMS endpoint are distinguished from unresolved details. - Why this condition is needed: This is needed to avoid turning the conventional magnitude of Hedges g into a validated MCID or a treatment benefit for PMDD or pregnancy. - Application exceptions: Do not recalculate the historical g=-0.53 and -0.52559 or C·50, or use them as condition-status scores. - Remaining uncertainty: Materials on a validated MCID, importance to patients, and applicability for the overall scale in question. Scope is limited to the currently retained records; no new judgment is made about clinical efficacy, an individual's probability of success, or safety. - Referenced methods: E05: M15 §15.3.1–15.3.3; custom application / E09: M03 §3.2.4; custom limits on extrapolation / E08: M03 §3.2.1–3.2.4; details of dose, duration, and effect modification are custom designs. Reason for applying this to the overall PMS score comparison: this is needed to avoid turning the conventional magnitude of Hedges g into a validated MCID or a treatment benefit for PMDD or pregnancy. No formal RoB2/GRADE assessment or clinical certification was performed. - Related sources: S02, S03 ### N35 · Is actual reading of local summaries distinguished from past access, external materials not read in this review, and the associated dates? Verification status: Met Reading scope: Summary reading: the specified original locations in the currently archived source summary were actually read. External originals and old separate copies were not read in this review. - Current findings: This review read the currently retained KO/EN manuscripts, 9 evidence entries, 21 bibliographic entries, and metadata. The original verified_date is 2026-09-15, and there is no actual-access-date key for each citation. Each material's access date is blank; the original review date is separate. External originals, separate indexes/ZIP files, and 127 were not read in this review. - Why unverified: This condition records the boundary between actual local actions and historical declarations. It does not directly certify the current contents of external materials. - Reason for missing information: Records of actual access, acquisition, and reading events, with material-specific dates and original locations - Required materials and conditions: Records of actual access, acquisition, and reading events, with material-specific dates and original locations - Materials to obtain first: Records of actual access, acquisition, and reading events, with material-specific dates and original locations - Further research: Review access events separately for each material, and add current actions and dates only when new reading is authorized. - Conditions for verification: Reading of currently archived summaries, report-specific historical access declarations, blank access dates, the original review date, and external access not attempted in this review are distinguished. - Why this condition is needed: This is needed to avoid treating verified_date or historical access_level as an actual access date for each material in this review or as evidence of full-text reading in this review. - Application exceptions: Do not treat a historical failed direct connection as an access failure in this review, or fill in missing date keys arbitrarily. - Remaining uncertainty: Records of actual access, acquisition, and reading events, with material-specific dates and original locations. Scope is limited to the currently retained records; no new judgment is made about clinical efficacy, an individual's probability of success, or safety. - Referenced methods: C03: data collection/selection principles in M04 §4.5–4.6; separation of access from reading and the hyperlink contract are custom designs / C09: M04 §4.5, §4.6.3; limits on transitioning to current materials are based on the user's scope and custom design. Reason for applying this to the overall PMS score comparison: this is needed to avoid treating verified_date or historical access_level as an actual access date for each material in this review or as evidence of full-text reading in this review. No formal RoB2/GRADE assessment or clinical certification was performed. - Related sources: S01, S02, S03, S04, S05, S06, S07, S08, S09, S10, S11, S12, S13, S14, S15, S16, S17, S18, S19, S20, S21 ### N36 · Are the original C·50 assessment and the different verdict and policy of historical composite record 127 kept separate from current condition statuses? Verification status: Met Reading scope: Summary reading: the specified original locations in the currently archived source summary were actually read. External originals and old separate copies were not read in this review. - Current findings: The judgment in the current manuscript is C·50, with axes B/P/R1/I1/E+/B2/CX. The combined PMS/pregnancy-nausea record in 127 and its B·60 are related history and have not been repurposed for the current PMS-only claim. Preserve the numbers and original metadata of the current original judgment unchanged. - Why unverified: The separation of current/historical judgments and the rule that they remain unchanged were verified. C·50 is not used as evidence that individual conditions are met. - Reason for missing information: Current judgment, relationships to related records, original axes and version metadata - Required materials and conditions: Current judgment, relationships to related records, original axes and version metadata - Materials to obtain first: Current judgment, relationships to related records, original axes and version metadata - Further research: When making a correction, preserve the original event, before-and-after values and version, and distinguish revision of the conditions from a change in the clinical judgment as separate tasks. - Conditions for verification: Preserve the original C·50, axes, related document quality and historical relationship to 127, without repurposing grades/axes/scores for new judgments. - Why this condition is needed: Preserving the original judgment does not issue an efficacy score or a checklist fulfillment rate for the new table. - Application exceptions: From 127, do not repurpose the B·60 judgment or pregnancy-nausea evidence, and do not open the original 127 file in this task. - Remaining uncertainty: Current judgment, relationships to related records, original axes and version metadata: this is the scope of the currently preserved record, without a new judgment of clinical efficacy, individual probability of success or safety. - Referenced methods: C01: Principles for clarifying the question in M03 §3.1, §3.2.1–3.2.4; detailed separation rules are self-designed / C09: M04 §4.5, §4.6.3; limits on the current conversion of materials follow the user-defined scope and self-designed rules. Reason for applying this to the overall PMS score comparison: Preserving the original judgment does not issue an efficacy score or a checklist fulfillment rate for the new table. No official RoB2/GRADE assessment or clinical certification was performed. - Related sources: ### N37 · Are statements of insufficiency or uncertainty linked to the scope of preservation, reference date and conditions for updating? Verification status: Met Reading scope: Summary reading: the specified original locations in the currently archived source summary were actually read. External originals and old separate copies were not read in this review. - Current findings: Record from the preservation-table review dated 2026-10-05: The original evidence reference date is 2026-09-15, and the review date for that work was 2026-10-05. Update conditions include dose, vitamer, hierarchy, scale, denominators, intervals, corrections, safety and recovery of the original location for the 80 mg/day record. The existing ZIP/calculation records were references only; no new search or effect calculation was performed. - Why unverified: The record of the scope verified and the update conditions was checked. This does not certify the completeness of the literature or the presence or absence of an effect. - Reason for missing information: Dates, the actual preserved records of search/selection/calculation, and the original location of each update event - Required materials and conditions: Dates, the actual preserved records of search/selection/calculation, and the original location of each update event - Materials to obtain first: Dates, the actual preserved records of search/selection/calculation, and the original location of each update event - Further research: When new materials are permitted and become available, compare their identity, scope and version, and review only the observations and status of the relevant conditions again. - Conditions for verification: Record the original reference date, the date of the current review, the scope of what remains unverified and specific update events. - Why this condition is needed: This is needed to avoid overstating gaps in the current summary as absence of research worldwide, an effect of 0, or a current comprehensive search. - Application exceptions: Do not label search, selection or calculation files in the old ZIP as materials actually read in this task. - Remaining uncertainty: Dates, the actual preserved records of search/selection/calculation, and the original location of each update event: this is the scope of the currently preserved record, without a new judgment of clinical efficacy, individual probability of success or safety. - Referenced methods: C09: M04 §4.5, §4.6.3; limits on the current conversion of materials follow the user-defined scope and self-designed rules / E06: M08 Table 8.2.a, M04 §4.6.3; self-designed application. Reason for applying this to the overall PMS score comparison: This is needed to avoid overstating gaps in the current summary as absence of research worldwide, an effect of 0, or a current comprehensive search. No official RoB2/GRADE assessment or clinical certification was performed. - Related sources: ## Evidence and sources ### S01 Wyatt et al. 1999. Efficacy of vitamin B-6 in the treatment of premenstrual syndrome: systematic review [Source](https://pmc.ncbi.nlm.nih.gov/articles/PMC27878/) Materials actually read: The corresponding Korean and English summaries and bibliographic records in the archived manuscript were read. The linked external original materials have not been read in this task. Findings recorded in the summary: Record at the time of preservation: This is an older review with mixed interventions and endpoints. It is not counted as a new independent trial. Record level: This is content recorded in the archived manuscript, not the result of a new comparison with the current external original materials. Independent replication: Link the original evidence families and explicitly stated same-trial/protocol relationships. Do not assign clinical trial families to reviews or general documents. Registry details and overlap between S19/S02 remain unverified. | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Full HTML text of the original review article | Currently unverified | Not attempted this time | Not read | The historical access date of each material is unverified. The archived manuscript’s review date, 2026-09-15, is not this file’s access date. Historical access level recorded for this physical material: full_text. Contextual level recorded for the containing document: full_text. This is an older review with mixed interventions and endpoints. It is not counted as a new independent trial. Original location: Abstract; Table 1; vitamin B6 alone subgroup; Discussion. The historical access level is recorded only when access to this physical material is explicitly stated in the source. Access to separate links, original full texts, indexed/print extracts or the whole PDF is not automatically inherited from the containing document’s access level. The archived summary was read in this task; the external material was not attempted, acquired or read. | ### S02 Ebrahimi et al. 2012. Effects of Magnesium and Vitamin B6 on the Severity of Premenstrual Syndrome Symptoms [Source](https://pmc.ncbi.nlm.nih.gov/articles/PMC4161081/) Materials actually read: The corresponding Korean and English summaries and bibliographic records in the archived manuscript were read. The linked external original materials have not been read in this task. Findings recorded in the summary: Record at the time of preservation: The full text was read through a search index, and direct repeat access was blocked. B6 dose unverified; 250 mg refers to magnesium. Actual comparison/role: Separate magnesium, B6-only and placebo arms; B6 dose not reported. Denominator: Allocated 42 per group; completed B6 36 and placebo 37; endpoint denominator unverified. Endpoint: Overall score from a separate 30-symptom diary; a different scale from the main trial. Result: B6 36.51→22.84, placebo 35.80→28.41; arithmetic change contrast -6.28 points; between-group change CI unverified. Funding: Coded tablets supplied by the university pharmacy verified; funding and author COI unverified. Limitations: Supportive evidence; not pooled with a different scale. Allocated 42 per group; completed B6 36/placebo 37; endpoint analysis denominator unverified. 250 mg refers to magnesium, and the B6 dose was not reported. The historical arithmetic -6.28 points is not pooled with the main 12-symptom scale. Record level: This is content recorded in the archived manuscript, not the result of a new comparison with the current external original materials. Independent replication: Link the original evidence families and explicitly stated same-trial/protocol relationships. Do not assign clinical trial families to reviews or general documents. Registry details and overlap between S19/S02 remain unverified. | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | PMC link to the original article (distinct from the historical indexed extract) | Currently unverified | Not attempted this time | Not read | The historical access date of each material is unverified. The archived manuscript’s review date, 2026-09-15, is not this file’s access date. Historical access level recorded for this physical material: Unverified. Contextual level recorded for the containing document: indexed_full_text. The full text was read through a search index, and direct repeat access was blocked. B6 dose unverified; 250 mg refers to magnesium. Original location: Methods; Results; Table 1; article registration header. The historical access level is recorded only when access to this physical material is explicitly stated in the source. Access to separate links, original full texts, indexed/print extracts or the whole PDF is not automatically inherited from the containing document’s access level. The archived summary was read in this task; the external material was not attempted, acquired or read. | | Indexed full-text extract at the time of preservation (separate copy not read in this task) | Currently unverified | Not attempted this time | Not read | The historical access date of each material is unverified. The archived manuscript’s review date, 2026-09-15, is not this file’s access date. Historical access level recorded for this physical material: indexed_full_text. Contextual level recorded for the containing document: indexed_full_text. The full text was read through a search index, and direct repeat access was blocked. B6 dose unverified; 250 mg refers to magnesium. Original location: Methods; Results; Table 1; article registration header. The historical access level is recorded only when access to this physical material is explicitly stated in the source. Access to separate links, original full texts, indexed/print extracts or the whole PDF is not automatically inherited from the containing document’s access level. The archived summary was read in this task; the external material was not attempted, acquired or read. The direct URL of this physical material is not preserved. A bibliographic link is not substituted for a direct file URL. | ### S03 Ghazanfarpour et al. 2017. Hypericum perforutum and Vitamin B6 as a Treatment for Premenstrual Syndrome [Source](https://brieflands.com/journals/jjnpp/articles/55301) Materials actually read: The corresponding Korean and English summaries and bibliographic records in the archived manuscript were read. The linked external original materials have not been read in this task. Findings recorded in the summary: Record at the time of preservation: Records of HTML/PDF acquisition and visual table checking were reused. B6 is a separate arm from Hypericum. Actual comparison/role: Parallel B6-only, Hypericum and placebo arms; only B6 and placebo are used for this effect. Denominator: Table analysis headers B6 78 and placebo 78; overall recruitment/allocation descriptions conflict. Endpoint: Overall total of the 12-symptom diary; lower is better; total-score normalization unverified. Result: Baseline→end B6 33.93→20.92, placebo 33.86→23.90; arithmetic change contrast -3.05 points; formal change-contrast CI unverified. Funding: Specific funding and B6 product supplier unverified; the authors’ no-conflict declaration is separate from proof of independent funding. Limitations: Main evidence; limitations in bias and measurement reporting. The preserved table has B6 33.93(SD 6.95)→20.92(SD 5.26), placebo 33.86(SD 6.16)→23.90(SD 6.00), with 78 per group. The historical arithmetic change contrast -3.05 points, end-of-treatment difference -2.98 points and end-of-treatment Hedges g=-0.53 are not an official adjusted change contrast or MCID. The original test P, detailed participant counts and tablet-strength wording are absent from the currently archived summary. Record level: This is content recorded in the archived manuscript, not the result of a new comparison with the current external original materials. Independent replication: Link the original evidence families and explicitly stated same-trial/protocol relationships. Do not assign clinical trial families to reviews or general documents. Registry details and overlap between S19/S02 remain unverified. | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Full HTML text of the original article on the publisher site | Currently unverified | Not attempted this time | Not read | The historical access date of each material is unverified. The archived manuscript’s review date, 2026-09-15, is not this file’s access date. Historical access level recorded for this physical material: full_text. Contextual level recorded for the containing document: full_text. Records of HTML/PDF acquisition and visual table checking were reused. B6 is a separate arm from Hypericum. Original location: PDF pp.1–3: Methods, Results, Table 1 Total row and footnote, Table 2; p.5 Footnotes/ref.8. The historical access level is recorded only when access to this physical material is explicitly stated in the source. Access to separate links, original full texts, indexed/print extracts or the whole PDF is not automatically inherited from the containing document’s access level. The archived summary was read in this task; the external material was not attempted, acquired or read. | | Full PDF of the original article (exact PDF URL currently unverified) | Currently unverified | Not attempted this time | Not read | The historical access date of each material is unverified. The archived manuscript’s review date, 2026-09-15, is not this file’s access date. Historical access level recorded for this physical material: full_text. Contextual level recorded for the containing document: full_text. Records of HTML/PDF acquisition and visual table checking were reused. B6 is a separate arm from Hypericum. Original location: PDF pp.1–3: Methods, Results, Table 1 Total row and footnote, Table 2; p.5 Footnotes/ref.8. The historical access level is recorded only when access to this physical material is explicitly stated in the source. Access to separate links, original full texts, indexed/print extracts or the whole PDF is not automatically inherited from the containing document’s access level. The archived summary was read in this task; the external material was not attempted, acquired or read. The direct URL of this physical material is not preserved. A bibliographic link is not substituted for a direct file URL. | ### S04 Doll, Brown, Thurston and Vessey 1989. Pyridoxine (vitamin B6) and the premenstrual syndrome: a randomized crossover trial [Source](https://pubmed.ncbi.nlm.nih.gov/2558186/) Materials actually read: The corresponding Korean and English summaries and bibliographic records in the archived manuscript were read. The linked external original materials have not been read in this task. Findings recorded in the summary: Record at the time of preservation: Abstract-level access. The original overall-score tables and paired variance could not be verified. Actual comparison/role: Pyridoxine 50 mg/day versus placebo; crossover design. Denominator: 63 entered; the full 7 months were completed by 32 participants; endpoint-specific denominators unverified. Endpoint: A 9-symptom diary; distinguish the emotional-domain signal from overall PMS. Result: The emotional-subdomain result is not repurposed as overall symptom improvement. Funding: Funding and COI unverified in the accessed abstract. Limitations: Qualitative evidence with a limited scope. Record level: This is content recorded in the archived manuscript, not the result of a new comparison with the current external original materials. Independent replication: Link the original evidence families and explicitly stated same-trial/protocol relationships. Do not assign clinical trial families to reviews or general documents. Registry details and overlap between S19/S02 remain unverified. | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | PubMed abstract | Currently unverified | Not attempted this time | Not read | The historical access date of each material is unverified. The archived manuscript’s review date, 2026-09-15, is not this file’s access date. Historical access level recorded for this physical material: abstract. Contextual level recorded for the containing document: abstract. Abstract-level access. The original overall-score tables and paired variance could not be verified. Original location: Abstract: design, entry/completion, emotional-symptom findings. The historical access level is recorded only when access to this physical material is explicitly stated in the source. Access to separate links, original full texts, indexed/print extracts or the whole PDF is not automatically inherited from the containing document’s access level. The archived summary was read in this task; the external material was not attempted, acquired or read. | | Full text of the original article (exact URL and historical full-text access currently unverified) | Currently unverified | Not attempted this time | Not read | The historical access date of each material is unverified. The archived manuscript’s review date, 2026-09-15, is not this file’s access date. Historical access level recorded for this physical material: Unverified. Contextual level recorded for the containing document: abstract. Abstract-level access. The original overall-score tables and paired variance could not be verified. Original location: Abstract: design, entry/completion, emotional-symptom findings. The historical access level is recorded only when access to this physical material is explicitly stated in the source. Access to separate links, original full texts, indexed/print extracts or the whole PDF is not automatically inherited from the containing document’s access level. The archived summary was read in this task; the external material was not attempted, acquired or read. The direct URL of this physical material is not preserved. A bibliographic link is not substituted for a direct file URL. | ### S05 Kendall and Schnurr 1987. The effects of vitamin B6 supplementation on premenstrual symptoms [Source](https://pubmed.ncbi.nlm.nih.gov/3299182/) Materials actually read: The corresponding Korean and English summaries and bibliographic records in the archived manuscript were read. The linked external original materials have not been read in this task. Findings recorded in the summary: Record at the time of preservation: Indexed abstract and secondary (2nd) extraction from reviews. The original overall-score mean is unverified. Actual comparison/role: Pyridoxine 150 mg/day versus placebo. Denominator: Review record of 55 completers; original endpoint denominator unverified. Endpoint: Mixed subdomains; original overall-score mean unverified. Result: The overall symptom mean and confidence interval could not be verified. Funding: Unverified; independence of the study is not assumed. Limitations: Secondary (2nd) extraction and limited qualitative material. Record level: This is content recorded in the archived manuscript, not the result of a new comparison with the current external original materials. Independent replication: Link the original evidence families and explicitly stated same-trial/protocol relationships. Do not assign clinical trial families to reviews or general documents. Registry details and overlap between S19/S02 remain unverified. | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | PubMed bibliographic/abstract link (distinct from the historical index) | Currently unverified | Not attempted this time | Not read | The historical access date of each material is unverified. The archived manuscript’s review date, 2026-09-15, is not this file’s access date. Historical access level recorded for this physical material: Unverified. Contextual level recorded for the containing document: indexed_abstract. Indexed abstract and secondary (2nd) extraction from reviews. The original overall-score mean is unverified. Original location: Indexed abstract; S01 Table 1 and S10 Table 1 for secondary details. The historical access level is recorded only when access to this physical material is explicitly stated in the source. Access to separate links, original full texts, indexed/print extracts or the whole PDF is not automatically inherited from the containing document’s access level. The archived summary was read in this task; the external material was not attempted, acquired or read. | | Indexed abstract/review extract at the time of preservation (separate copy not read in this task) | Currently unverified | Not attempted this time | Not read | The historical access date of each material is unverified. The archived manuscript’s review date, 2026-09-15, is not this file’s access date. Historical access level recorded for this physical material: indexed_abstract. Contextual level recorded for the containing document: indexed_abstract. Indexed abstract and secondary (2nd) extraction from reviews. The original overall-score mean is unverified. Original location: Indexed abstract; S01 Table 1 and S10 Table 1 for secondary details. The historical access level is recorded only when access to this physical material is explicitly stated in the source. Access to separate links, original full texts, indexed/print extracts or the whole PDF is not automatically inherited from the containing document’s access level. The archived summary was read in this task; the external material was not attempted, acquired or read. The direct URL of this physical material is not preserved. A bibliographic link is not substituted for a direct file URL. | ### S06 Kashanian et al. 2007. Pyridoxine (vitamin B6) therapy for premenstrual syndrome [Source](https://pubmed.ncbi.nlm.nih.gov/17187801/) Materials actually read: The corresponding Korean and English summaries and bibliographic records in the archived manuscript were read. The linked external original materials have not been read in this task. Findings recorded in the summary: Record at the time of preservation: Metadata-access records are distinguished from the numbers in the request to resume the work. The 80 mg/day, -1.80 versus -0.93, and an initial 160 with 94 analysed were preserved but not used for grading because the original result location and dispersion were not recovered. Actual comparison/role: Preserved record of pyridoxine 80 mg/day versus placebo; salt and exact formulation unverified. Denominator: Preserved record of an initial 160 with 94 analysed; stage-specific and per-arm denominators unverified. Endpoint: Values carried as overall PMS change; exact scale and original text location not recovered. Result: -1.80 versus -0.93 preserved, arithmetic difference -0.87; no SD/CI/p values invented. Funding: Funding, product supply and COI unverified; an author was added by correction in 2020. Limitations: Preservation of carried values only; not used for new original-source verification, grading or independent replication. The 80 mg/day, B6 -1.80 versus placebo -0.93, initial 160 with 94 analysed, and historical arithmetic -0.87 points are values carried in the request to resume the work. Per-arm denominators/dispersion/original Results location were not recovered, so these were not used as new verification, for grading or as replication. Record level: This is content recorded in the archived manuscript, not the result of a new comparison with the current external original materials. Independent replication: Link the original evidence families and explicitly stated same-trial/protocol relationships. Do not assign clinical trial families to reviews or general documents. Registry details and overlap between S19/S02 remain unverified. | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | PubMed bibliographic link (original result location not recovered) | Currently unverified | Not attempted this time | Not read | The historical access date of each material is unverified. The archived manuscript’s review date, 2026-09-15, is not this file’s access date. Historical access level recorded for this physical material: metadata. Contextual level recorded for the containing document: metadata. Metadata-access records are distinguished from the numbers in the request to resume the work. The 80 mg/day, -1.80 versus -0.93, and initial 160 with 94 analysed were preserved but not used for grading because the original result location and dispersion were not recovered. Original location: Bibliographic record; secondary trial description in review literature. The historical access level is recorded only when access to this physical material is explicitly stated in the source. Access to separate links, original full texts, indexed/print extracts or the whole PDF is not automatically inherited from the containing document’s access level. The archived summary was read in this task; the external material was not attempted, acquired or read. | | Full text of the original article (exact original Results location and historical full-text access unverified) | Currently unverified | Not attempted this time | Not read | The historical access date of each material is unverified. The archived manuscript’s review date, 2026-09-15, is not this file’s access date. Historical access level recorded for this physical material: Unverified. Contextual level recorded for the containing document: metadata. Metadata-access records are distinguished from the numbers in the request to resume the work. The 80 mg/day, -1.80 versus -0.93, and initial 160 with 94 analysed were preserved but not used for grading because the original result location and dispersion were not recovered. Original location: Bibliographic record; secondary trial description in review literature. The historical access level is recorded only when access to this physical material is explicitly stated in the source. Access to separate links, original full texts, indexed/print extracts or the whole PDF is not automatically inherited from the containing document’s access level. The archived summary was read in this task; the external material was not attempted, acquired or read. The direct URL of this physical material is not preserved. A bibliographic link is not substituted for a direct file URL. | ### S07 Kashanian et al. 2020. Corrigendum to Pyridoxine (vitamin B6) therapy for premenstrual syndrome [Source](https://obgyn.onlinelibrary.wiley.com/doi/10.1002/ijgo.13157) Materials actually read: The corresponding Korean and English summaries and bibliographic records in the archived manuscript were read. The linked external original materials have not been read in this task. Findings recorded in the summary: Record at the time of preservation: This is a correction adding an author in 2020. It was not described as a numerical correction or a retraction. Record level: This is content recorded in the archived manuscript, not the result of a new comparison with the current external original materials. Independent replication: Link the original evidence families and explicitly stated same-trial/protocol relationships. Do not assign clinical trial families to reviews or general documents. Registry details and overlap between S19/S02 remain unverified. | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Link to the correction adding an author | Currently unverified | Not attempted this time | Not read | The historical access date of each material is unverified. The archived manuscript’s review date, 2026-09-15, is not this file’s access date. Historical access level recorded for this physical material: full_text. Contextual level recorded for the containing document: full_text. This is a correction adding an author in 2020. It was not described as a numerical correction or a retraction. Original location: Corrigendum text and corrected author list. The historical access level is recorded only when access to this physical material is explicitly stated in the source. Access to separate links, original full texts, indexed/print extracts or the whole PDF is not automatically inherited from the containing document’s access level. The archived summary was read in this task; the external material was not attempted, acquired or read. | ### S08 Retallick-Brown, Blampied and Rucklidge 2020. A Pilot Randomized Treatment-Controlled Trial Comparing Vitamin B6 with Broad-Spectrum Micronutrients for Premenstrual Syndrome [Source](https://pubmed.ncbi.nlm.nih.gov/31928364/) Materials actually read: The corresponding Korean and English summaries and bibliographic records in the archived manuscript were read. The linked external original materials have not been read in this task. Findings recorded in the summary: Record at the time of preservation: This used an active comparator, and the review describes inclusion of riboflavin. It is not a strict B6-only versus placebo comparison. Actual comparison/role: Broad-spectrum micronutrients versus a B6 comparator; the review also describes riboflavin. Denominator: Not used as a denominator for the present B6-only versus placebo effect. Endpoint: Do not mix modified DRSP with other scales or comparison specifications. Result: Excluded from the direct effect because there was no placebo and the strict monotherapy condition was not met. Funding: Original funding and COI unverified; no additional credit for independence. Limitations: Excluded evidence. Record level: This is content recorded in the archived manuscript, not the result of a new comparison with the current external original materials. Independent replication: Link the original evidence families and explicitly stated same-trial/protocol relationships. Do not assign clinical trial families to reviews or general documents. Registry details and overlap between S19/S02 remain unverified. | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | PubMed bibliographic link (active comparator/composition cross-checked in a review) | Currently unverified | Not attempted this time | Not read | The historical access date of each material is unverified. The archived manuscript’s review date, 2026-09-15, is not this file’s access date. Historical access level recorded for this physical material: metadata. Contextual level recorded for the containing document: metadata. This used an active comparator, and the review describes inclusion of riboflavin. It is not a strict B6-only versus placebo comparison. Original location: Bibliographic record; design and composition cross-checked in S10 Table 1. The historical access level is recorded only when access to this physical material is explicitly stated in the source. Access to separate links, original full texts, indexed/print extracts or the whole PDF is not automatically inherited from the containing document’s access level. The archived summary was read in this task; the external material was not attempted, acquired or read. | ### S09 De Souza et al. 2000. Magnesium plus vitamin B6 and anxiety-related premenstrual symptoms [Source](https://pubmed.ncbi.nlm.nih.gov/10746516/) Materials actually read: The corresponding Korean and English summaries and bibliographic records in the archived manuscript were read. The linked external original materials have not been read in this task. Findings recorded in the summary: Record at the time of preservation: The anxiety subdomain result for a combination intervention is not the overall PMS effect of B6 alone. Possible report overlap was handled conservatively. Actual comparison/role: Distinguish magnesium, B6, combination and placebo crossover data. Denominator: Not counted as a new denominator for the present overall-severity effect. Endpoint: The anxiety subdomain and overall severity are separate. Result: Do not repurpose the combination-intervention anxiety result as overall symptoms with B6 alone. Funding: Unverified. Limitations: Limited scope; excluded from the direct effect. Record level: This is content recorded in the archived manuscript, not the result of a new comparison with the current external original materials. Independent replication: Link the original evidence families and explicitly stated same-trial/protocol relationships. Do not assign clinical trial families to reviews or general documents. Registry details and overlap between S19/S02 remain unverified. | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | PubMed bibliographic link (combination-intervention anxiety result) | Currently unverified | Not attempted this time | Not read | The historical access date of each material is unverified. The archived manuscript’s review date, 2026-09-15, is not this file’s access date. Historical access level recorded for this physical material: metadata. Contextual level recorded for the containing document: metadata. The anxiety subdomain result for a combination intervention is not the overall PMS effect of B6 alone. Possible report overlap was handled conservatively. Original location: Bibliographic record; S01 and S10 trial tables for related crossover material. The historical access level is recorded only when access to this physical material is explicitly stated in the source. Access to separate links, original full texts, indexed/print extracts or the whole PDF is not automatically inherited from the containing document’s access level. The archived summary was read in this task; the external material was not attempted, acquired or read. | ### S10 Robinson et al. 2025 (online 2024). Effect of nutritional interventions on the psychological symptoms of premenstrual syndrome in women of reproductive age: a systematic review of randomized controlled trials [Source](https://pmc.ncbi.nlm.nih.gov/articles/PMC11723155/) Materials actually read: The corresponding Korean and English summaries and bibliographic records in the archived manuscript were read. The linked external original materials have not been read in this task. Findings recorded in the summary: Record at the time of preservation: Used for identifying updates and cross-checking. Psychological symptoms and overall symptom severity are different endpoints. Record level: This is content recorded in the archived manuscript, not the result of a new comparison with the current external original materials. Independent replication: Link the original evidence families and explicitly stated same-trial/protocol relationships. Do not assign clinical trial families to reviews or general documents. Registry details and overlap between S19/S02 remain unverified. | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Full HTML text of the original review article | Currently unverified | Not attempted this time | Not read | The historical access date of each material is unverified. The archived manuscript’s review date, 2026-09-15, is not this file’s access date. Historical access level recorded for this physical material: full_text. Contextual level recorded for the containing document: full_text. Used for identifying updates and cross-checking. Psychological symptoms and overall symptom severity are different endpoints. Original location: Table 1, vitamin B6 rows; discussion and risk-of-bias sections. The historical access level is recorded only when access to this physical material is explicitly stated in the source. Access to separate links, original full texts, indexed/print extracts or the whole PDF is not automatically inherited from the containing document’s access level. The archived summary was read in this task; the external material was not attempted, acquired or read. | ### S11 Ghazanfarpour et al. 2011. Hypericum perforatum for the treatment of premenstrual syndrome [Source](https://doi.org/10.1016/j.ijgo.2010.11.007) Materials actually read: The corresponding Korean and English summaries and bibliographic records in the archived manuscript were read. The linked external original materials have not been read in this task. Findings recorded in the summary: Record at the time of preservation: Explicitly identified as an earlier partial report of S03, so it belongs to the same trial family. The original full text was not acquired. Record level: This is content recorded in the archived manuscript, not the result of a new comparison with the current external original materials. Independent replication: Link the original evidence families and explicitly stated same-trial/protocol relationships. Do not assign clinical trial families to reviews or general documents. Registry details and overlap between S19/S02 remain unverified. | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | DOI bibliographic link (original full text not historically acquired) | Currently unverified | Not attempted this time | Not read | The historical access date of each material is unverified. The archived manuscript’s review date, 2026-09-15, is not this file’s access date. Historical access level recorded for this physical material: Unverified. Contextual level recorded for the containing document: metadata. Explicitly identified as an earlier partial report of S03, so it belongs to the same trial family. The original full text was not acquired. Original location: S03 Methods statement and reference 8. The historical access level is recorded only when access to this physical material is explicitly stated in the source. Access to separate links, original full texts, indexed/print extracts or the whole PDF is not automatically inherited from the containing document’s access level. The archived summary was read in this task; the external material was not attempted, acquired or read. | ### S12 TGA 2026. Medicines containing vitamin B6 (pyridoxine, pyridoxal or pyridoxamine) [Source](https://www.tga.gov.au/news/safety-updates/medicines-containing-vitamin-b6-pyridoxine-pyridoxal-or-pyridoxamine) Materials actually read: The corresponding Korean and English summaries and bibliographic records in the archived manuscript were read. The linked external original materials have not been read in this task. Findings recorded in the summary: Record at the time of preservation: The change to pharmacist-only status for above 50 mg~up to 200 mg/day was scheduled to take effect on 2027-06-01 and was not treated as a regulation in force at the reference date. Record level: This is content recorded in the archived manuscript, not the result of a new comparison with the current external original materials. Independent replication: Link the original evidence families and explicitly stated same-trial/protocol relationships. Do not assign clinical trial families to reviews or general documents. Registry details and overlap between S19/S02 remain unverified. | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Full text of the official TGA webpage | Currently unverified | Not attempted this time | Not read | The historical access date of each material is unverified. The archived manuscript’s review date, 2026-09-15, is not this file’s access date. Historical access level recorded for this physical material: full_text. Contextual level recorded for the containing document: full_text. The change to pharmacist-only status for above 50 mg~up to 200 mg/day was scheduled to take effect on 2027-06-01 and was not treated as a regulation in force at the reference date. Original location: Published 19 February 2026, updated 7 April 2026; scheduling and neuropathy sections. The historical access level is recorded only when access to this physical material is explicitly stated in the source. Access to separate links, original full texts, indexed/print extracts or the whole PDF is not automatically inherited from the containing document’s access level. The archived summary was read in this task; the external material was not attempted, acquired or read. | ### S13 TGA 2026. Are you unknowingly taking too much vitamin B6? [Source](https://www.tga.gov.au/news/blog/are-you-unknowingly-taking-too-much-vitamin-b6) Materials actually read: The corresponding Korean and English summaries and bibliographic records in the archived manuscript were read. The linked external original materials have not been read in this task. Findings recorded in the summary: Record at the time of preservation: Official safety information on neuropathy and cumulative intake, not PMS efficacy evidence. Record level: This is content recorded in the archived manuscript, not the result of a new comparison with the current external original materials. Independent replication: Link the original evidence families and explicitly stated same-trial/protocol relationships. Do not assign clinical trial families to reviews or general documents. Registry details and overlap between S19/S02 remain unverified. | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Full text of the official TGA webpage | Currently unverified | Not attempted this time | Not read | The historical access date of each material is unverified. The archived manuscript’s review date, 2026-09-15, is not this file’s access date. Historical access level recorded for this physical material: full_text. Contextual level recorded for the containing document: full_text. Official safety information on neuropathy and cumulative intake, not PMS efficacy evidence. Original location: 4 March 2026; peripheral neuropathy, cumulative intake, irreversible injury and stopping advice. The historical access level is recorded only when access to this physical material is explicitly stated in the source. Access to separate links, original full texts, indexed/print extracts or the whole PDF is not automatically inherited from the containing document’s access level. The archived summary was read in this task; the external material was not attempted, acquired or read. | ### S14 EFSA 2023. Scientific opinion on the tolerable upper intake level for vitamin B6 [Source](https://www.efsa.europa.eu/en/efsajournal/pub/8006) Materials actually read: The corresponding Korean and English summaries and bibliographic records in the archived manuscript were read. The linked external original materials have not been read in this task. Findings recorded in the summary: Record at the time of preservation: The upper intake level of 12 mg/day in the officially linked full text concerns chronic total intake, not a treatment dose. Record level: This is content recorded in the archived manuscript, not the result of a new comparison with the current external original materials. Independent replication: Link the original evidence families and explicitly stated same-trial/protocol relationships. Do not assign clinical trial families to reviews or general documents. Registry details and overlap between S19/S02 remain unverified. | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | EFSA official literature link (distinct from the linked Wiley full text) | Currently unverified | Not attempted this time | Not read | The historical access date of each material is unverified. The archived manuscript’s review date, 2026-09-15, is not this file’s access date. Historical access level recorded for this physical material: Unverified. Contextual level recorded for the containing document: full_text. The upper intake level of 12 mg/day in the officially linked full text concerns chronic total intake, not a treatment dose. Original location: Abstract; Conclusions, adult UL derivation. The historical access level is recorded only when access to this physical material is explicitly stated in the source. Access to separate links, original full texts, indexed/print extracts or the whole PDF is not automatically inherited from the containing document’s access level. The archived summary was read in this task; the external material was not attempted, acquired or read. | | Linked original Wiley full text (exact URL currently unverified) | Currently unverified | Not attempted this time | Not read | The historical access date of each material is unverified. The archived manuscript’s review date, 2026-09-15, is not this file’s access date. Historical access level recorded for this physical material: full_text. Contextual level recorded for the containing document: full_text. The upper intake level of 12 mg/day in the officially linked full text concerns chronic total intake, not a treatment dose. Original location: Abstract; Conclusions, adult UL derivation. The historical access level is recorded only when access to this physical material is explicitly stated in the source. Access to separate links, original full texts, indexed/print extracts or the whole PDF is not automatically inherited from the containing document’s access level. The archived summary was read in this task; the external material was not attempted, acquired or read. The direct URL of this physical material is not preserved. A bibliographic link is not substituted for a direct file URL. | ### S15 NIH ODS. Vitamin B6: Fact Sheet for Health Professionals [Source](https://ods.od.nih.gov/factsheets/VitaminB6-HealthProfessional/) Materials actually read: The corresponding Korean and English summaries and bibliographic records in the archived manuscript were read. The linked external original materials have not been read in this task. Findings recorded in the summary: Record at the time of preservation: Direct-request errors occurred, so only content accessed through an index or print view was used. It does not establish the salt used in the trial. Record level: This is content recorded in the archived manuscript, not the result of a new comparison with the current external original materials. Independent replication: Link the original evidence families and explicitly stated same-trial/protocol relationships. Do not assign clinical trial families to reviews or general documents. Registry details and overlap between S19/S02 remain unverified. | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | NIH official full-webpage link (distinct from historical index/print access) | Currently unverified | Not attempted this time | Not read | The historical access date of each material is unverified. The archived manuscript’s review date, 2026-09-15, is not this file’s access date. Historical access level recorded for this physical material: Unverified. Contextual level recorded for the containing document: indexed_text. Direct-request errors occurred, so only content accessed through an index or print view was used. It does not establish the salt used in the trial. Original location: Vitamin forms; Recommended Intakes; Health Risks from Excessive Vitamin B6. The historical access level is recorded only when access to this physical material is explicitly stated in the source. Access to separate links, original full texts, indexed/print extracts or the whole PDF is not automatically inherited from the containing document’s access level. The archived summary was read in this task; the external material was not attempted, acquired or read. | | Indexed/print content at the time of preservation (separate copy not read in this task) | Currently unverified | Not attempted this time | Not read | The historical access date of each material is unverified. The archived manuscript’s review date, 2026-09-15, is not this file’s access date. Historical access level recorded for this physical material: indexed_text. Contextual level recorded for the containing document: indexed_text. Direct-request errors occurred, so only content accessed through an index or print view was used. It does not establish the salt used in the trial. Original location: Vitamin forms; Recommended Intakes; Health Risks from Excessive Vitamin B6. The historical access level is recorded only when access to this physical material is explicitly stated in the source. Access to separate links, original full texts, indexed/print extracts or the whole PDF is not automatically inherited from the containing document’s access level. The archived summary was read in this task; the external material was not attempted, acquired or read. The direct URL of this physical material is not preserved. A bibliographic link is not substituted for a direct file URL. | ### S16 MedlinePlus. Pyridoxine drug information [Source](https://medlineplus.gov/druginfo/meds/a682587.html) Materials actually read: The corresponding Korean and English summaries and bibliographic records in the archived manuscript were read. The linked external original materials have not been read in this task. Findings recorded in the summary: Record at the time of preservation: Used to check medicines, supplements and special populations; no PMS efficacy recommendation was imported. Record level: This is content recorded in the archived manuscript, not the result of a new comparison with the current external original materials. Independent replication: Link the original evidence families and explicitly stated same-trial/protocol relationships. Do not assign clinical trial families to reviews or general documents. Registry details and overlap between S19/S02 remain unverified. | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Full text of the official MedlinePlus webpage | Currently unverified | Not attempted this time | Not read | The historical access date of each material is unverified. The archived manuscript’s review date, 2026-09-15, is not this file’s access date. Historical access level recorded for this physical material: full_text. Contextual level recorded for the containing document: full_text. Used to check medicines, supplements and special populations; no PMS efficacy recommendation was imported. Original location: Special precautions; side effects; revised 15 August 2017. The historical access level is recorded only when access to this physical material is explicitly stated in the source. Access to separate links, original full texts, indexed/print extracts or the whole PDF is not automatically inherited from the containing document’s access level. The archived summary was read in this task; the external material was not attempted, acquired or read. | ### S17 ACOG 2023. Management of Premenstrual Disorders, Clinical Practice Guideline No. 7 [Source](https://www.acog.org/clinical/clinical-guidance/clinical-practice-guideline/articles/2023/12/management-of-premenstrual-disorders) Materials actually read: The corresponding Korean and English summaries and bibliographic records in the archived manuscript were read. The linked external original materials have not been read in this task. Findings recorded in the summary: Record at the time of preservation: Full-text access to the guideline failed. Its recommendations were not used for efficacy grading. It is separate from pregnancy-nausea guidance. Record level: This is content recorded in the archived manuscript, not the result of a new comparison with the current external original materials. Independent replication: Link the original evidence families and explicitly stated same-trial/protocol relationships. Do not assign clinical trial families to reviews or general documents. Registry details and overlap between S19/S02 remain unverified. | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | ACOG guideline literature link (historical full-text access failed) | Currently unverified | Not attempted this time | Not read | The historical access date of each material is unverified. The archived manuscript’s review date, 2026-09-15, is not this file’s access date. Historical access level recorded for this physical material: access_failed. Contextual level recorded for the containing document: access_failed. Full-text access to the guideline failed. Its recommendations were not used for efficacy grading. It is separate from pregnancy-nausea guidance. Original location: Bibliographic identity and official URL only. The historical access level is recorded only when access to this physical material is explicitly stated in the source. Access to separate links, original full texts, indexed/print extracts or the whole PDF is not automatically inherited from the containing document’s access level. The archived summary was read in this task; the external material was not attempted, acquired or read. | ### S18 IRCT201106216854N1 registration pointer [Source](https://trialsearch.who.int/Trial2.aspx?TrialID=IRCT201106216854N1) Materials actually read: The corresponding Korean and English summaries and bibliographic records in the archived manuscript were read. The linked external original materials have not been read in this task. Findings recorded in the summary: Record at the time of preservation: The registration identifier appears in the original article, but registry details, history and whether registration was prospective could not be verified. Record level: This is content recorded in the archived manuscript, not the result of a new comparison with the current external original materials. Independent replication: Link the original evidence families and explicitly stated same-trial/protocol relationships. Do not assign clinical trial families to reviews or general documents. Registry details and overlap between S19/S02 remain unverified. | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | WHO registration-record link (detailed history unverified) | Currently unverified | Not attempted this time | Not read | The historical access date of each material is unverified. The archived manuscript’s review date, 2026-09-15, is not this file’s access date. Historical access level recorded for this physical material: access_failed. Contextual level recorded for the containing document: access_failed. The registration identifier appears in the original article, but registry details, history and whether registration was prospective could not be verified. Original location: Registration number in S02 article header. The historical access level is recorded only when access to this physical material is explicitly stated in the source. Access to separate links, original full texts, indexed/print extracts or the whole PDF is not automatically inherited from the containing document’s access level. The archived summary was read in this task; the external material was not attempted, acquired or read. | ### S19 Fathizadeh et al. 2010. Evaluating the effect of magnesium and magnesium plus vitamin B6 supplement on the severity of premenstrual syndrome [Source](https://pmc.ncbi.nlm.nih.gov/articles/PMC3208934/) Materials actually read: The corresponding Korean and English summaries and bibliographic records in the archived manuscript were read. The linked external original materials have not been read in this task. Findings recorded in the summary: Record at the time of preservation: Excluded because this was a combination trial. Possible overlap with S02 is unverified, and it was not counted as independent replication. Actual comparison/role: Comparisons such as magnesium versus magnesium+B6. Denominator: Not added as participants in an independent B6-only replication. Endpoint: Not an overall effect of B6 alone. Result: Excluded from the direct effect because this was a combination intervention. Funding: Unverified. Limitations: Excluded; overlap with S02 unverified. Record level: This is content recorded in the archived manuscript, not the result of a new comparison with the current external original materials. Independent replication: Link the original evidence families and explicitly stated same-trial/protocol relationships. Do not assign clinical trial families to reviews or general documents. Registry details and overlap between S19/S02 remain unverified. | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | PMC original-article link (historical verification was indexed bibliographic information) | Currently unverified | Not attempted this time | Not read | The historical access date of each material is unverified. The archived manuscript’s review date, 2026-09-15, is not this file’s access date. Historical access level recorded for this physical material: Unverified. Contextual level recorded for the containing document: metadata. Excluded because this was a combination trial. Possible overlap with S02 is unverified, and it was not counted as independent replication. Original location: Indexed title/metadata and related trial discussion. The historical access level is recorded only when access to this physical material is explicitly stated in the source. Access to separate links, original full texts, indexed/print extracts or the whole PDF is not automatically inherited from the containing document’s access level. The archived summary was read in this task; the external material was not attempted, acquired or read. | ### S20 2025. Comparison of the Effects of Vitagnus, Soy, and Vitagnus-soy Capsules on the Severity of Premenstrual Syndrome [Source](https://ijcbnm.sums.ac.ir/article_50585_7dd12040edca4d010200928714a1ba05.pdf) Materials actually read: The corresponding Korean and English summaries and bibliographic records in the archived manuscript were read. The linked external original materials have not been read in this task. Findings recorded in the summary: Record at the time of preservation: Excluded as a false-positive search result with no B6 intervention. Actual comparison/role: Vitagnus, soy and combination; no B6 arm. Denominator: Not counted as participants for a B6 effect. Endpoint: Not applicable to the present B6 endpoint. Result: Excluded as a wrong-intervention search result. Funding: No separate funding extraction was performed for this excluded study. Limitations: Excluded. Record level: This is content recorded in the archived manuscript, not the result of a new comparison with the current external original materials. Independent replication: Link the original evidence families and explicitly stated same-trial/protocol relationships. Do not assign clinical trial families to reviews or general documents. Registry details and overlap between S19/S02 remain unverified. | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Original-article PDF link (historical verification was the p.1 abstract section) | Currently unverified | Not attempted this time | Not read | The historical access date of each material is unverified. The archived manuscript’s review date, 2026-09-15, is not this file’s access date. Historical access level recorded for this physical material: Unverified. Contextual level recorded for the containing document: full_text. Excluded as a false-positive search result with no B6 intervention. Original location: PDF p.1 abstract visually checked. The historical access level is recorded only when access to this physical material is explicitly stated in the source. Access to separate links, original full texts, indexed/print extracts or the whole PDF is not automatically inherited from the containing document’s access level. The archived summary was read in this task; the external material was not attempted, acquired or read. | ### S21 Retallick-Brown et al. 2016. Micronutrients for premenstrual symptoms: study protocol [Source](https://www.mdpi.com/2305-6320/3/4/32) Materials actually read: The corresponding Korean and English summaries and bibliographic records in the archived manuscript were read. The linked external original materials have not been read in this task. Findings recorded in the summary: Record at the time of preservation: Access was restricted, and this was grouped as the protocol for S08. It is not a separate trial or effect. Record level: This is content recorded in the archived manuscript, not the result of a new comparison with the current external original materials. Independent replication: Link the original evidence families and explicitly stated same-trial/protocol relationships. Do not assign clinical trial families to reviews or general documents. Registry details and overlap between S19/S02 remain unverified. | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | MDPI protocol link (historical direct 429 response/indexed information) | Currently unverified | Not attempted this time | Not read | The historical access date of each material is unverified. The archived manuscript’s review date, 2026-09-15, is not this file’s access date. Historical access level recorded for this physical material: access_failed. Contextual level recorded for the containing document: access_failed. Access was restricted, and this was grouped as the protocol for S08. It is not a separate trial or effect. Original location: Indexed protocol information only. The historical access level is recorded only when access to this physical material is explicitly stated in the source. Access to separate links, original full texts, indexed/print extracts or the whole PDF is not automatically inherited from the containing document’s access level. The archived summary was read in this task; the external material was not attempted, acquired or read. | ## Review criteria and methods These are Chamgap's own application conditions, informed by the relevant sections of official methodological guidance. They do not constitute official assessment-tool certification or a new efficacy score. - M03 [Cochrane Handbook 6.5 (2024), chapter updated 2023-08](https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-03) · §3.1, §3.2.1–3.2.3, MECIR C5/C7/C13 · Clearly record the question, eligibility conditions and reasons for changes, and distinguish variations of the intervention. · Historical reuse, from 1585, of the original-byte/SHA inspection copies and principles of the 5 methodological HTML documents. This is not a new reading of the full methods texts or an official assessment/certification. - M04 [Cochrane Handbook 6.5.1 (2025), chapter updated 2025-03](https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-04) · §4.5, §4.6.1–4.6.3, MECIR C42 · Distinguish studies from reports and link them; do not omit a study solely because a result was not reported. · Historical reuse, from 1585, of the original-byte/SHA inspection copies and principles of the 5 methodological HTML documents. This is not a new reading of the full methods texts or an official assessment/certification. - M08 [Cochrane Handbook 6.5 (2024), chapter updated 2019-10](https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-08) · §8.1–8.2.3, Table 8.2.a · Fix the outcome and effect of interest when reviewing randomization, deviations, missing data, measurement and selective reporting. · Historical reuse, from 1585, of the original-byte/SHA inspection copies and principles of the 5 methodological HTML documents. This is not a new reading of the full methods texts or an official assessment/certification. - M15 [Cochrane Handbook 6.5 (2024), chapter updated 2023-08](https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-15) · §15.2.4, §15.3.1–15.3.3 · Distinguish effect estimates, intervals, importance and applicability. Sample size alone does not determine precision. · Historical reuse, from 1585, of the original-byte/SHA inspection copies and principles of the 5 methodological HTML documents. This is not a new reading of the full methods texts or an official assessment/certification. - M19 [Cochrane Handbook 6.5 (2024), chapter updated 2019-10](https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-19) · §19.1.2, §19.2.1–19.2.4 · Harm questions may require different designs, populations and follow-up from efficacy questions. Case reports do not establish incidence. · Historical reuse, from 1585, of the original-byte/SHA inspection copies and principles of the 5 methodological HTML documents. This is not a new reading of the full methods texts or an official assessment/certification. ## What the statuses mean - Met: The specific narrow condition concerning identity, attribution of numbers, records or interpretive boundaries is met. This does not certify a clinical effect, absence of risk or current verification of external full texts. - Partly verified: Some substantive content is available, but verification of the question’s product, diagnosis, denominators, analysis/materials is incomplete. - Unverified: Cannot be established within the currently preserved scope. This does not mean an effect of 0, absence of research worldwide or an access failure in this task. - Conflicting records: Inconsistent reports of the same fact remain. Successful preservation of a conflict is distinguished from verification of actual consistency. - Not reported: Not reported only within the explicitly identified content obtained at that time. Do not extend this to the entire full text that has not been read in this task. - Not applicable: Use only when there is a reason the condition does not apply to the current claim. This is not a substitute for unverified or unread. - Inaccessible: Distinguish an actual failure in this task from a historical failure. Do not assign this to external materials not attempted in this task. - Review incomplete: Limited to the fact that current external comparison has not been performed. This does not mean that reading of the local archived summaries or individual judgments actually completed is incomplete. ## Change history 2026-11-01 · Public page/materials 1.0. The public view and materials were prepared from the existing 37 items. No new clinical search, change in verification status or scoring was performed.