# Oral dispersible methylcobalamin (vitamin B12) × Reduction in reported painDETECT score in metformin-treated diabetic neuropathy with low B12 Verdict 3111 · Evidence Check Stored-material review date: 2026-10-05 Original evidence date: 2026-09-16 Review-criteria version: NGM-v3111-METHYL-B12-METFORMIN-PAINDETECT12M-1.0 Public page/material preparation date: 2026-11-05 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: Adults with type 2 diabetes and confirmed peripheral and autonomic neuropathy; metformin for ≥4 years, B12 <400 pmol/L; stable HbA1c of 6.5–7.5%; pain threshold for entry unverified - Ingredient, formulation and route: Methylcobalamin (mecobalamin), vitamin B12 as the single added active ingredient · B12 fix, UNI-PHARMA; oral dispersible tablet. Historical trial batch and placebo excipients unverified · Oral dispersible formulation; no sublingual holding time is inferred and no injection route is substituted - Dose: 1000 µg, 1 time daily; total product intake and dietary exposure unverified - Comparator: Similar-looking placebo; stable common glycemic management, restrictions on other analgesics and occasional paracetamol permitted - Measured outcome: Primary endpoint selected for this page: between-group comparison of change in reported painDETECT score at 12 months; whether it was the registered primary (1st) endpoint is unverified - Duration: 12 months - Questions outside this scope: Mean pain NRS/VAS; Analgesic efficacy in diabetic neuropathy generally; Supplementation in all patients with absolute deficiency or normal B12; Optimal dose and persistence after discontinuation; Replacement of analgesics and prevention of clinical events; Efficacy of other cobalamins, injections or multicomponent products; Independent determination of harm incidence or causality ## Checklist items ### N01 · Which population and which 12-month score are being compared? Verification status: Met Reading scope: Summary read: the actual locations and values in the current retained summary for case 3111 were read. Access to external or older separate source materials was not attempted in this exercise; they were neither acquired nor read - Current findings: The single question is whether adding oral methylcobalamin 1000 µg/day for 12 months lowers the reported painDETECT score compared with placebo on the same background management in adults with type 2 diabetes and confirmed peripheral and autonomic neuropathy who have used metformin for at least 4 years and have B12 <400 pmol/L. The actual subclaims list is empty. - Why unverified: The identity and exclusions of the original question were verified. This does not mean that efficacy or a general analgesic effect has been established. - Reason for missing information: Pain entry criteria, the exact scale version and the adjusted effect estimate remain unverified in separate rows. - Required materials and conditions: The original question and specifications of the population, ingredient, route, dose, comparator, time point and endpoint - Materials to obtain first: The original question and specifications of the population, ingredient, route, dose, comparator, time point and endpoint - Further research: Fix the original question and eligibility criteria, then separately examine only comparisons involving the same population, formulation and score. - Conditions for verification: Link the population, methylcobalamin, placebo and 12-month painDETECT comparison in the original /ko/effect and fixed question. - Why this condition is needed: The B12 effects discussed across the page must be distinguished from the selected score comparison. - Application exceptions: The actual subclaims list is empty. Mean pain NRS, all diabetic neuropathy and replacement of analgesics are not added as new subclaims. - Remaining uncertainty: The identity and exclusions of the original question were verified. This does not mean that efficacy or a general analgesic effect has been established. - Referenced methods: M03 §3.1, §3.2.1–3.2.4 principles for clarifying the question; detailed separation rules are internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations for each question are internally designed — An internally developed, item-specific adaptation for Separate question. No official methodological tool was applied or certification performed. - Related sources: S01, S04 ### N02 · Was methylcobalamin the trial's single active ingredient? Verification status: Met Reading scope: Summary read: the actual locations and values in the current retained summary for case 3111 were read. Access to external or older separate source materials was not attempted in this exercise; they were neither acquired nor read - Current findings: The manuscript records methylcobalamin (mecobalamin) as the single added active ingredient. Other cobalamins were not combined with it, and B12 fix is identified as a single-ingredient oral product. - Why unverified: The retained identity of the chemical form and single added ingredient was verified. Product purity and the trial batch were not verified. - Reason for missing information: The historical manufacturing batch and purity are unverified. - Required materials and conditions: The original trial's active ingredient, chemical form and whether it was a combination product - Materials to obtain first: The original trial's active ingredient, chemical form and whether it was a combination product - Further research: Compare the active-ingredient specifications with each original trial's composition to distinguish comparisons of a single added ingredient in the same chemical form. - Conditions for verification: Identify methylcobalamin/mecobalamin as the actual added ingredient and distinguish it from other cobalamins. - Why this condition is needed: Needed to avoid combining effects of different chemical forms or combination products solely on the basis of the name B12. - Application exceptions: Cyanocobalamin, hydroxocobalamin and B-vitamin combinations are not direct evidence for this single-ingredient methylcobalamin comparison. - Remaining uncertainty: The retained identity of the chemical form and single added ingredient was verified. Product purity and the trial batch were not verified. - Referenced methods: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed — An internally developed, item-specific adaptation for Active ingredient. No official methodological tool was applied or certification performed. - Related sources: S01 ### N03 · Do the supply identity and historical batch of B12 fix match? Verification status: Partly verified Reading scope: Summary read: the actual locations and values in the current retained summary for case 3111 were read. Access to external or older separate source materials was not attempted in this exercise; they were neither acquired nor read - Current findings: B12 fix and UNI-PHARMA are identified in the retained manuscript. Manufacturing source, historical trial batch and purity are unverified; the current manufacturer page is not used as evidence that the trial batch was identical. - Why unverified: Only the product name and supplier were linked. Comparison of the batch, purity and identity with the current product remains outstanding. - Reason for missing information: Historical trial-batch, purity and manufacturing-source documentation is absent. - Required materials and conditions: Trial-product supply records, batch/purity documentation and the current product description - Materials to obtain first: Trial-product supply records, batch/purity documentation and the current product description - Further research: Obtain the trial supply records and contemporaneous batch documentation, and compare them with the current product description while distinguishing their dates. - Conditions for verification: Record the trial product name and supplier, the current manufacturer description, and historical batch and purity separately. - Why this condition is needed: Needed to avoid treating the current product page as verification of the historical trial batch. - Application exceptions: Linking the UNI-PHARMA name and B12 fix page does not independently confirm the historical batch, purity or efficacy. - Remaining uncertainty: Only the product name and supplier were linked. Comparison of the batch, purity and identity with the current product remains outstanding. - Referenced methods: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed — An internally developed, item-specific adaptation for Trial product. No official methodological tool was applied or certification performed. - Related sources: S01, S10 ### N04 · Has the oral dispersible formulation been reinterpreted as sublingual or injectable? Verification status: Met Reading scope: Summary read: the actual locations and values in the current retained summary for case 3111 were read. Access to external or older separate source materials was not attempted in this exercise; they were neither acquired nor read - Current findings: The actual formulation is an oral dispersible tablet. No sublingual holding time is inferred and no injection route is substituted. - Why unverified: The retained identity of the oral formulation and route was linked. Detailed dosing procedures or absorption mechanisms were not verified. - Reason for missing information: A sublingual holding time is not inferred from the manuscript, and historical batch details are unverified. - Required materials and conditions: Trial administration method and oral dispersible formulation specifications - Materials to obtain first: Trial administration method and oral dispersible formulation specifications - Further research: Compare the contemporaneous administration instructions to distinguish the dosing procedure from the actual route. - Conditions for verification: Preserve the actual oral dispersible formulation and route without filling in an unreported sublingual holding time. - Why this condition is needed: A formulation that disperses in the mouth cannot be assumed to have the same administration route as sublingual holding or injection. - Application exceptions: Do not add a sublingual holding time, injection route or absorption mechanism absent from the source material. - Remaining uncertainty: The retained identity of the oral formulation and route was linked. Detailed dosing procedures or absorption mechanisms were not verified. - Referenced methods: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed — An internally developed, item-specific adaptation for Route of administration. No official methodological tool was applied or certification performed. - Related sources: S01 ### N05 · Has the trial dose been distinguished from total exposure? Verification status: Partly verified Reading scope: Summary read: the actual locations and values in the current retained summary for case 3111 were read. Access to external or older separate source materials was not attempted in this exercise; they were neither acquired nor read - Current findings: The trial administered methylcobalamin alone at 1000 µg 1 time daily for 12 months. Total exposure including diet, fortified foods and other additional supplements, and numerical adherence, are unverified. - Why unverified: The nominal trial dose and frequency were linked, but actual total exposure and adherence were not verified. - Reason for missing information: Exposure from diet, fortified foods and additional supplements, and numerical adherence, are unverified. - Required materials and conditions: Trial dose and frequency, dietary/additional supplementation exposure and adherence records - Materials to obtain first: Trial dose and frequency, dietary/additional supplementation exposure and adherence records - Further research: Compare administration, additional supplementation and dietary records by group to assess differences between nominal dose and actual exposure. - Conditions for verification: Distinguish the trial dose of 1000 µg 1 time daily from total exposure including diet and additional supplementation. - Why this condition is needed: Needed to avoid turning the trial's nominal dose into an individual dosing instruction or actual total intake. - Application exceptions: 1000 µg/day is a trial condition, not an instruction for personal use or a change in diabetes medication. - Remaining uncertainty: The nominal trial dose and frequency were linked, but actual total exposure and adherence were not verified. - Referenced methods: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed; M03 §3.2.3, M08 §8.2.2–8.2.3; internal application — An internally developed, item-specific adaptation for Nominal dose. No official methodological tool was applied or certification performed. - Related sources: S01 ### N06 · Has the manufacturer's 1000 µg versus 1000 mg labeling been resolved? Verification status: Conflicting information Reading scope: Summary read: the actual locations and values in the current retained summary for case 3111 were read. Access to external or older separate source materials was not attempted in this exercise; they were neither acquired nor read - Current findings: The retained manuscript records that the current manufacturer page displays both 1000 µg and 1000 mg. This conflict remains unresolved; the trial dose remains 1000 µg/day as specified in S01. - Why unverified: The manuscript explicitly records inconsistent units on the same product page. Which label, if any, was corrected was not checked in this exercise. - Reason for missing information: A correction resolving the current product-label conflict and comparison with the historical batch are unverified. - Required materials and conditions: Locations of the manufacturer's labels, corrections and contemporaneous trial-dose documentation - Materials to obtain first: Locations of the manufacturer's labels, corrections and contemporaneous trial-dose documentation - Further research: Compare labeling and correction history on the same product page with their original locations to verify the conflict, while maintaining the trial specifications separately. - Conditions for verification: Preserve both printed units on the current product page and handle them separately from the trial dose. - Why this condition is needed: Needed to avoid silently harmonizing conflicting product units or substituting them for the trial dose. - Application exceptions: The conflict on the current product page does not justify changing the original trial's 1000 µg/day to 1000 mg/day. - Remaining uncertainty: The manuscript explicitly records inconsistent units on the same product page. Which label, if any, was corrected was not checked in this exercise. - Referenced methods: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed; M04 §4.6.3, M15 §15.3.1–15.3.3; the separation of statuses is internally designed — An internally developed, item-specific adaptation for Conflicting product units. No official methodological tool was applied or certification performed. - Related sources: S01, S10 ### N07 · Has 12-month administration been separated from results over other durations? Verification status: Met Reading scope: Summary read: the actual locations and values in the current retained summary for case 3111 were read. Access to external or older separate source materials was not attempted in this exercise; they were neither acquired nor read - Current findings: The selected question and actual trial duration are 12 months. The 4-month nerve-conduction result in S05 is separated as a different duration and endpoint. Observation over 12 months is not reinterpreted as persistence after discontinuation. - Why unverified: The selected time point and duration were linked, with the timing of adjacent results distinguished. The preregistered primary time point remains separately unverified. - Reason for missing information: Registered assessment times and follow-up after discontinuation are unverified. - Required materials and conditions: Trial administration and assessment times, and the duration of each adjacent study - Materials to obtain first: Trial administration and assessment times, and the duration of each adjacent study - Further research: Compare the original time-specific tables and trial schedule to separate administration duration, observation duration and the time point of the selected outcome. - Conditions for verification: Link the selected score's 12-month time point and administration period without combining the adjacent 4-month result with it. - Why this condition is needed: Studies cannot be counted as direct replications when durations and measurements differ, even if they use the same neuropathy label. - Application exceptions: The 4-month nerve-conduction result in S05 is a different outcome from this 12-month painDETECT comparison. - Remaining uncertainty: The selected time point and duration were linked, with the timing of adjacent results distinguished. The preregistered primary time point remains separately unverified. - Referenced methods: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations for each question are internally designed — An internally developed, item-specific adaptation for Observation period. No official methodological tool was applied or certification performed. - Related sources: S01, S05 ### N08 · Which adults with diabetic neuropathy were selected? Verification status: Partly verified Reading scope: Summary read: the actual locations and values in the current retained summary for case 3111 were read. Access to external or older separate source materials was not attempted in this exercise; they were neither acquired nor read - Current findings: The population comprises adults with type 2 diabetes and confirmed peripheral and autonomic neuropathy who have used metformin for at least 4 years and have B12 <400 pmol/L. This scope is not extended to all diabetic neuropathy. - Why unverified: The core population-selection criteria were preserved, but the pain threshold for entry and minimum duration were not verified. - Reason for missing information: Pain entry criteria, minimum duration and detailed implementation of selection are unverified. - Required materials and conditions: Population diagnoses, duration of metformin use and B12 eligibility criterion - Materials to obtain first: Population diagnoses, duration of metformin use and B12 eligibility criterion - Further research: Compare inclusion/exclusion documentation and baseline characteristics to assess the applicability boundaries of the narrowly selected population. - Conditions for verification: Link the actual selection criteria: type 2 diabetes, confirmed peripheral and autonomic neuropathy, metformin for ≥4 years and low B12. - Why this condition is needed: Needed to avoid automatically applying the results to all patients with diabetic neuropathy. - Application exceptions: Do not extend the selected population with low B12 and long-term metformin use to diabetes generally or to populations with normal B12. - Remaining uncertainty: The core population-selection criteria were preserved, but the pain threshold for entry and minimum duration were not verified. - Referenced methods: M03 §3.2.1; detailed population criteria are internally designed — An internally developed, item-specific adaptation for Population selection. No official methodological tool was applied or certification performed. - Related sources: S01 ### N09 · Is B12 <400 pmol/L being interpreted as absolute deficiency in everyone? Verification status: Partly verified Reading scope: Summary read: the actual locations and values in the current retained summary for case 3111 were read. Access to external or older separate source materials was not attempted in this exercise; they were neither acquired nor read - Current findings: The manuscript retains B12 <400 pmol/L as the eligibility criterion. This is not reclassified as confirmed absolute deficiency in everyone or used as evidence for supplementation in all patients with normal B12. - Why unverified: The low-B12 selection boundary was linked, but diagnoses of absolute deficiency and effects in a normal-B12 population were not verified. - Reason for missing information: Individual deficiency diagnoses, baseline distribution and direct comparisons in a normal-B12 population are unverified. - Required materials and conditions: Baseline B12 criterion, diagnosis of deficiency and population-specific results - Materials to obtain first: Baseline B12 criterion, diagnosis of deficiency and population-specific results - Further research: Compare diagnostic evidence of deficiency with the eligibility value, and assess extension to a normal-B12 population through a separate comparison. - Conditions for verification: Distinguish the trial's low-B12 criterion from confirmed absolute deficiency and the effects of supplementation in people with normal B12. - Why this condition is needed: A low eligibility value and correction of confirmed deficiency are different questions of applicability. - Application exceptions: Do not classify every participant as having confirmed absolute deficiency solely on the basis of B12 <400 pmol/L. - Remaining uncertainty: The low-B12 selection boundary was linked, but diagnoses of absolute deficiency and effects in a normal-B12 population were not verified. - Referenced methods: M03 §3.2.1; detailed population criteria are internally designed; M03 §3.2.1–3.2.4; details on dose, duration and effect modification are internally designed — An internally developed, item-specific adaptation for Low-B12 boundary. No official methodological tool was applied or certification performed. - Related sources: S01 ### N10 · Were the pain NRS entry threshold and minimum duration verified? Verification status: Unverified Reading scope: Summary read: the actual locations and values in the current retained summary for case 3111 were read. Access to external or older separate source materials was not attempted in this exercise; they were neither acquired nor read - Current findings: The authors' description of painful neuropathy is preserved, but the entry NRS criterion and minimum pain duration are unverified. - Why unverified: The exact pain entry criteria cannot be established within the retained material read. This does not mean that participants did not experience pain. - Reason for missing information: Documentation of the pain NRS entry threshold, minimum duration and diagnostic implementation is absent. - Required materials and conditions: Pain diagnosis, entry NRS criterion and minimum duration in the eligibility documentation - Materials to obtain first: Pain diagnosis, entry NRS criterion and minimum duration in the eligibility documentation - Further research: Compare the eligibility documentation and diagnostic procedures to verify actual pain-intensity and duration entry criteria. - Conditions for verification: Distinguish the description of painful neuropathy from the verification status of the exact pain threshold and duration for entry. - Why this condition is needed: The description 'painful' alone does not establish a population with a particular pain intensity or duration of chronic pain. - Application exceptions: Do not reinterpret unverified entry criteria as a population without pain or absence of analgesic efficacy. - Remaining uncertainty: The exact pain entry criteria cannot be established within the retained material read. This does not mean that participants did not experience pain. - Referenced methods: M03 §3.2.1; detailed population criteria are internally designed; M08 Table 8.2.a, M03 §3.2.4; internal application — An internally developed, item-specific adaptation for Pain entry criteria. No official methodological tool was applied or certification performed. - Related sources: S01 ### N11 · Was selection for stable HbA1c of 6.5–7.5% preserved? Verification status: Partly verified Reading scope: Summary read: the actual locations and values in the current retained summary for case 3111 were read. Access to external or older separate source materials was not attempted in this exercise; they were neither acquired nor read - Current findings: The original population is described as adults with stable HbA1c of 6.5–7.5%. Background glycemic management was maintained; the same score effect is not generalized to patients with other glycemic states. - Why unverified: The retained stability criterion and range were linked, but details of actual glycemic-medication changes and management by group are lacking. - Reason for missing information: Detailed records of actual glycemic-medication changes and management exposure by group are unverified. - Required materials and conditions: Baseline glycemic status, stability criteria and glycemic-medication records by group - Materials to obtain first: Baseline glycemic status, stability criteria and glycemic-medication records by group - Further research: Compare baseline glycemic selection criteria and management/medication records by group to assess applicability and concomitant-treatment boundaries. - Conditions for verification: Link the stable HbA1c range with the population receiving common glycemic management. - Why this condition is needed: Needed to avoid applying the result of adjunctive treatment on stable glycemic management to all glycemic states. - Application exceptions: A nonsignificant result for HbA1c change is not a direct substitute for this stable-range selection criterion or the painDETECT result. - Remaining uncertainty: The retained stability criterion and range were linked, but details of actual glycemic-medication changes and management by group are lacking. - Referenced methods: M03 §3.2.1; detailed population criteria are internally designed; M03 §3.2.3, M08 §8.2.2–8.2.3; internal application — An internally developed, item-specific adaptation for Glycemic-status selection. No official methodological tool was applied or certification performed. - Related sources: S01 ### N12 · Was the full composition of the similar-looking placebo verified? Verification status: Partly verified Reading scope: Summary read: the actual locations and values in the current retained summary for case 3111 were read. Access to external or older separate source materials was not attempted in this exercise; they were neither acquired nor read - Current findings: The comparator conditions are a similar-looking placebo and stable common glycemic management. Full placebo excipients and the historical batch are unverified. - Why unverified: The framework of the placebo comparison was linked, but full composition and batch identity were not verified. - Reason for missing information: Documentation of full placebo excipients, batch and implementation of blinding is unverified. - Required materials and conditions: Placebo appearance, composition and batch, and common management in each group - Materials to obtain first: Placebo appearance, composition and batch, and common management in each group - Further research: Compare contemporaneous placebo specifications and manufacturing records to assess comparator composition and implementation of blinding. - Conditions for verification: Record the similar-looking placebo comparison separately from the unverified full excipient composition. - Why this condition is needed: Needed to avoid confusing similar appearance with complete placebo identity or biological inactivity. - Application exceptions: Do not conclude that the placebo was an active treatment or that blinding was broken because its full composition is unverified. - Remaining uncertainty: The framework of the placebo comparison was linked, but full composition and batch identity were not verified. - Referenced methods: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed; M03 §3.2.3, M08 §8.2.2–8.2.3; internal application; M08 Table 8.2.a, M03 §3.2.4; internal application — An internally developed, item-specific adaptation for Placebo specifications. No official methodological tool was applied or certification performed. - Related sources: S01 ### N13 · Were common glycemic management and adjustment variables distinguished? Verification status: Partly verified Reading scope: Summary read: the actual locations and values in the current retained summary for case 3111 were read. Access to external or older separate source materials was not attempted in this exercise; they were neither acquired nor read - Current findings: Background glycemic management was maintained, and the formal comparison of change adjusted for HbA1c and glycemic medications. A common management policy and actual changes by group are different information; detailed change records are unverified. - Why unverified: The policy and adjustment variables were linked, but detailed comparison of actual concomitant exposure by group and the handling of changes remains outstanding. - Reason for missing information: Glycemic-medication changes by group, details of the adjustment model and specification of the effect of interest are unverified. - Required materials and conditions: Glycemic medications and management changes by group, and ANCOVA adjustment specifications - Materials to obtain first: Glycemic medications and management changes by group, and ANCOVA adjustment specifications - Further research: Compare concomitant-treatment changes by group and analysis specifications to assess the selected intervention's contribution and the effect of interest. - Conditions for verification: Record the common management policy, actual treatment changes by group, and adjustment for HbA1c/glycemic medications separately. - Why this condition is needed: Needed to avoid using a common policy as proof that all actual treatments were identical. - Application exceptions: Do not indicate that all differences in concomitant treatment, confounding and adherence were resolved merely because adjustment variables were used. - Remaining uncertainty: The policy and adjustment variables were linked, but detailed comparison of actual concomitant exposure by group and the handling of changes remains outstanding. - Referenced methods: M03 §3.2.3, M08 §8.2.2–8.2.3; internal application; M08 §8.2.2, M15 §15.3.1; internal application — An internally developed, item-specific adaptation for Common treatment. No official methodological tool was applied or certification performed. - Related sources: S01 ### N14 · Is the policy permitting paracetamol the same as actual use? Verification status: Partly verified Reading scope: Summary read: the actual locations and values in the current retained summary for case 3111 were read. Access to external or older separate source materials was not attempted in this exercise; they were neither acquired nor read - Current findings: The retained policy restricted other analgesics and permitted occasional paracetamol for only 2–3 days. The actual amount of rescue medication used is unverified. - Why unverified: The analgesic policy was verified, but actual amounts used by group and handling in the analysis were not verified. - Reason for missing information: Data on the amount and frequency of paracetamol use by group and handling in the analysis are unverified. - Required materials and conditions: Rescue-analgesic policy, amount used and changes by group, and handling in the analysis - Materials to obtain first: Rescue-analgesic policy, amount used and changes by group, and handling in the analysis - Further research: Compare rescue-medication use records by group to assess the relationship between the score comparison and concurrent treatment. - Conditions for verification: Distinguish restrictions on other analgesics and occasional paracetamol permitted for 2–3 days from the actual amounts used by group. - Why this condition is needed: A permission rule alone cannot establish that actual analgesic exposure was identical between groups. - Application exceptions: Do not interpret the policy restricting analgesics as an effect replacing analgesics, or fill in actual use as 0. - Remaining uncertainty: The analgesic policy was verified, but actual amounts used by group and handling in the analysis were not verified. - Referenced methods: M03 §3.2.3, M08 §8.2.2–8.2.3; internal application — An internally developed, item-specific adaptation for Rescue analgesics. No official methodological tool was applied or certification performed. - Related sources: S01 ### N15 · Were numerical adherence and additional B12 exposure verified? Verification status: Unverified Reading scope: Summary read: the actual locations and values in the current retained summary for case 3111 were read. Access to external or older separate source materials was not attempted in this exercise; they were neither acquired nor read - Current findings: Diet, fortified foods, total additional-supplement exposure and numerical adherence are unverified. The report that everyone completed 12 months does not guarantee actual intake or full adherence. - Why unverified: The material read contains no numerical data on actual exposure or adherence. Unverified information is not treated as proof of nonadherence or absence of additional supplementation. - Reason for missing information: Numerical adherence, diet and additional-supplement exposure data by group are lacking. - Required materials and conditions: Dosing records and numerical adherence by group, and records of diet, fortified foods and additional supplementation - Materials to obtain first: Dosing records and numerical adherence by group, and records of diet, fortified foods and additional supplementation - Further research: Compare dosing, diet and additional-exposure records, and assess their handling in relation to the effect of interest. - Conditions for verification: Distinguish nominal administration from actual dosing, diet, fortified foods and other supplementation exposure. - Why this condition is needed: Needed because reported completion by everyone differs from actual adherence. - Application exceptions: Do not substitute 90 fully adherent participants or identical total intake for the 90 reported completers. - Remaining uncertainty: The material read contains no numerical data on actual exposure or adherence. Unverified information is not treated as proof of nonadherence or absence of additional supplementation. - Referenced methods: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed; M03 §3.2.3, M08 §8.2.2–8.2.3; internal application — An internally developed, item-specific adaptation for Adherence and diet. No official methodological tool was applied or certification performed. - Related sources: S01 ### N16 · Is the painDETECT total score a mean pain-intensity NRS? Verification status: Met Reading scope: Summary read: the actual locations and values in the current retained summary for case 3111 were read. Access to external or older separate source materials was not attempted in this exercise; they were neither acquired nor read - Current findings: The original paper-form total score in S04 has a range of −1–38. It sums sensory qualities, pain course and radiation; the items recording pain intensity are not included in the total score. The selected painDETECT score is not a mean pain NRS/VAS. - Why unverified: The retained scale components and endpoint boundaries were verified. The exact language/version used in the trial and an applicable criterion for clinically important change remain separately unverified. - Reason for missing information: The exact questionnaire language/version used in the trial and clinical importance are unverified. - Required materials and conditions: Original scale definition, total-score components, range and direction - Materials to obtain first: Original scale definition, total-score components, range and direction - Further research: Compare the original scale definition with the items actually used in the trial to assess how the total score relates to the intensity items. - Conditions for verification: Distinguish the screening composite of sensory qualities, pain course and radiation from items recording pain intensity. - Why this condition is needed: Needed to avoid elevating a screening total score to a reduction in mean pain NRS/VAS. - Application exceptions: Preserve the scale's original screening purpose while retaining the comparison of the patient-reported score itself selected for this page. - Remaining uncertainty: The retained scale components and endpoint boundaries were verified. The exact language/version used in the trial and an applicable criterion for clinically important change remain separately unverified. - Referenced methods: M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations for each question are internally designed; M08 Table 8.2.a, M03 §3.2.4; internal application; M03 §3.2.4; internally defined boundaries for extending the claim — An internally developed, item-specific adaptation for Scale definition. No official methodological tool was applied or certification performed. - Related sources: S01, S04 ### N17 · Were the trial questionnaire's language, version and recall period verified? Verification status: Unverified Reading scope: Summary read: the actual locations and values in the current retained summary for case 3111 were read. Access to external or older separate source materials was not attempted in this exercise; they were neither acquired nor read - Current findings: The exact questionnaire language, version and recall period are unverified. A historical record of reading the original painDETECT definition does not substitute for the trial's actual questionnaire implementation. - Why unverified: The trial's measurement implementation cannot be established from the stored materials read. This is not a judgment that the scale is invalid. - Reason for missing information: The questionnaire language, version, recall period and scoring procedure are unverified. - Required materials and conditions: Trial questionnaire, language/translation, version, recall period and scoring procedure - Materials to obtain first: Trial questionnaire, language/translation, version, recall period and scoring procedure - Further research: Compare the contemporaneous questionnaire and scoring procedure with the original scale definition to assess how the actual measurement corresponds to it. - Conditions for verification: Distinguish the original scale description from the verification status of the language, version and recall period actually used in the trial. - Why this condition is needed: The original scale definition does not verify all aspects of how measurement was actually implemented in the trial. - Application exceptions: Do not infer the trial questionnaire version or recall period from the original scale's total-score range. - Remaining uncertainty: The trial's measurement implementation cannot be established from the stored materials read. This is not a judgment that the scale is invalid. - Referenced methods: M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations for each question are internally designed; M08 Table 8.2.a, M03 §3.2.4; internal application — An internally developed, item-specific adaptation for Questionnaire implementation. No official methodological tool was applied or certification performed. - Related sources: S01, S04 ### N18 · Was the page's primary endpoint at 12 months distinguished from a registered primary (1st) endpoint? Verification status: Partly verified Reading scope: Summary read: the actual locations and values in the current retained summary for case 3111 were read. Access to external or older separate source materials was not attempted in this exercise; they were neither acquired nor read - Current findings: The selected outcome is the between-group comparison of change in reported painDETECT score at 12 months. It is the page's primary endpoint, but whether it was prespecified as primary (1st) in the original registration is unverified. - Why unverified: The reported time point and the page's selection were verified, but the preregistered hierarchy could not be compared. - Reason for missing information: The registration's initial posting, amendment history and pain-endpoint hierarchy are unverified. - Required materials and conditions: Outcome time points, original registration hierarchy, initial posting and amendment history - Materials to obtain first: Outcome time points, original registration hierarchy, initial posting and amendment history - Further research: Compare the initial registration and timing of outcome reporting to assess how selection occurred and why changes were made. - Conditions for verification: Record the reported score at 12 months selected for this page separately from the verification status of the preregistered primary endpoint. - Why this condition is needed: Needed to avoid automatically turning the page's primary endpoint into a preregistered primary (1st) outcome. - Application exceptions: Do not reinterpret an unverified registration hierarchy as confirmed absence of registration or confirmed selective reporting. - Remaining uncertainty: The reported time point and the page's selection were verified, but the preregistered hierarchy could not be compared. - Referenced methods: M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations for each question are internally designed; M08 Table 8.2.a, M04 §4.6.3; internal application — An internally developed, item-specific adaptation for Selected time point. No official methodological tool was applied or certification performed. - Related sources: S01, S03 ### N19 · Was the RCT designation distinguished from implementation of allocation concealment? Verification status: Partly verified Reading scope: Summary read: the actual locations and values in the current retained summary for case 3111 were read. Access to external or older separate source materials was not attempted in this exercise; they were neither acquired nor read - Current findings: The original trial is retained as randomized, placebo-controlled and double-blind. How allocation concealment was implemented was not reported and was included in the original B2 rationale separately from the small trial size. - Why unverified: The design designation and limitations in the original assessment were linked. Detailed implementation was not compared, and no new bias-assessment tool was applied. - Reason for missing information: Detailed source documentation of allocation concealment and implementation of blinding is unverified. - Required materials and conditions: Original trial design, allocation/concealment, implementation of blinding and baseline data - Materials to obtain first: Original trial design, allocation/concealment, implementation of blinding and baseline data - Further research: Compare allocation procedures, placebo specifications and assessment-blinding documentation to assess potential bias in the selected score. - Conditions for verification: Link the randomized, placebo-controlled, double-blind design and the unreported implementation of allocation concealment to each outcome. - Why this condition is needed: Needed because a design designation alone cannot establish absence of allocation or measurement bias. - Application exceptions: Do not present unreported implementation of allocation concealment as actual concealment failure or an established magnitude of bias. - Remaining uncertainty: The design designation and limitations in the original assessment were linked. Detailed implementation was not compared, and no new bias-assessment tool was applied. - Referenced methods: M08 §8.1–8.2.3; internal application; M08 Table 8.2.a, M03 §3.2.4; internal application — An internally developed, item-specific adaptation for Allocation and blinding. No official methodological tool was applied or certification performed. - Related sources: S01 ### N20 · Are allocation of 90 participants, 44/46 by group, and completion being read as analysis denominators? Verification status: Partly verified Reading scope: Summary read: the actual locations and values in the current retained summary for case 3111 were read. Access to external or older separate source materials was not attempted in this exercise; they were neither acquired nor read - Current findings: Of 90 participants, 44 were allocated to methylcobalamin and 46 to placebo; all reportedly completed 12 months. Separate endpoint-specific analysis denominators were not reported. - Why unverified: The retained allocation and completion values were linked, but the actual painDETECT analysis denominators were not verified. - Reason for missing information: Endpoint-specific measurement and analysis denominators and documentation of exclusions/missing-data handling are unverified. - Required materials and conditions: Flow diagram and denominators for allocation, completion, measurement and analysis by group - Materials to obtain first: Flow diagram and denominators for allocation, completion, measurement and analysis by group - Further research: Compare the flow diagram and endpoint-specific analysis tables to link participant counts for allocation → completion → measurement → analysis. - Conditions for verification: Preserve allocation and reported completion of 44/46 separately from endpoint-specific analysis denominators. - Why this condition is needed: Needed to avoid automatically using a statement that everyone completed the trial as the analysis denominator for each outcome. - Application exceptions: Do not treat the 90 reported completers as a verified painDETECT analysis n=90 or group-specific n=44/46. - Remaining uncertainty: The retained allocation and completion values were linked, but the actual painDETECT analysis denominators were not verified. - Referenced methods: M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; adaptations for each study design are internally designed; M08 §8.2.2, M15 §15.3.1; internal application — An internally developed, item-specific adaptation for Allocation and completion. No official methodological tool was applied or certification performed. - Related sources: S01 ### N21 · Were the painDETECT analysis population and missing-data handling verified? Verification status: Unverified Reading scope: Summary read: the actual locations and values in the current retained summary for case 3111 were read. Access to external or older separate source materials was not attempted in this exercise; they were neither acquired nor read - Current findings: Endpoint-specific analysis denominators were not reported. Reported completion of 44/46 does not establish ITT, PP or 0 missing data; the original assessment also did not provide a standardized effect for endpoint values because the denominators were unverified. - Why unverified: The analysis population and missing-data handling for the selected score cannot be established from the material read. These are distinguished from the report that everyone completed the trial. - Reason for missing information: Exact analysis n, ITT/PP, reasons for missing data/exclusions and handling specifications are unverified. - Required materials and conditions: PainDETECT analysis denominators by group, analysis population, reasons for missing data/exclusions and their handling - Materials to obtain first: PainDETECT analysis denominators by group, analysis population, reasons for missing data/exclusions and their handling - Further research: Compare outcome-specific analysis specifications and missing-data/exclusion records to assess the effect of interest and the actual analysis population. - Conditions for verification: Distinguish endpoint-specific analysis populations, ITT/PP and missing-data handling from reported completion. - Why this condition is needed: Needed to avoid filling in absent analysis populations and denominators as ITT or all completers. - Application exceptions: Do not arbitrarily label an unreported analysis population as ITT/PP or fill in dropouts and missing data as 0. - Remaining uncertainty: The analysis population and missing-data handling for the selected score cannot be established from the material read. These are distinguished from the report that everyone completed the trial. - Referenced methods: M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; adaptations for each study design are internally designed; M08 §8.2.2, M15 §15.3.1; internal application — An internally developed, item-specific adaptation for Analysis population and missing data. No official methodological tool was applied or certification performed. - Related sources: S01 ### N22 · Are the original scores, existing change contrast and endpoint difference being read as the same estimate? Verification status: Met Reading scope: Summary read: the actual locations and values in the current retained summary for case 3111 were read. Access to external or older separate source materials was not attempted in this exercise; they were neither acquired nor read - Current findings: Table 4 reports scores of 18.4→17.1 in the methylcobalamin group and 19.3→20.9 in the placebo group. The manuscript's simple change contrast of −2.9 points and endpoint difference of −3.8 points are existing unadjusted descriptive values; neither is an unreported adjusted estimate. No new calculation was performed in this exercise. - Why unverified: The definitions, directions and attribution of the original scores and existing descriptive differences were preserved. The formal adjusted effect estimate and CI were not verified. - Reason for missing information: The formal adjusted coefficient, SE, CI and endpoint-specific analysis denominators are unverified. - Required materials and conditions: Scores and time points in the original results table, definitions of existing descriptive differences and adjusted results - Materials to obtain first: Scores and time points in the original results table, definitions of existing descriptive differences and adjusted results - Further research: Compare the original table and analysis definitions to assess the correspondence among original scores, descriptive differences and the formal adjusted effect. - Conditions for verification: Preserve 18.4→17.1 versus 19.3→20.9 and the manuscript's descriptive values of −2.9/−3.8 separately. - Why this condition is needed: Needed to avoid confusing within-group change, between-group difference in change, endpoint difference and an adjusted coefficient. - Application exceptions: Do not present the existing −2.9 and −3.8 as new calculations or unreported adjusted estimates. - Remaining uncertainty: The definitions, directions and attribution of the original scores and existing descriptive differences were preserved. The formal adjusted effect estimate and CI were not verified. - Referenced methods: M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations for each question are internally designed; M04 §4.6.3, M15 §15.3.1–15.3.3; the separation of statuses is internally designed; M08 §8.2.2, M15 §15.3.1; internal application — An internally developed, item-specific adaptation for Original scores and descriptive differences. No official methodological tool was applied or certification performed. - Related sources: S01 ### N23 · Has P<0.001 been turned into an adjusted coefficient, SE or CI? Verification status: Partly verified Reading scope: Summary read: the actual locations and values in the current retained summary for case 3111 were read. Access to external or older separate source materials was not attempted in this exercise; they were neither acquired nor read - Current findings: The formal comparison of change adjusted for HbA1c and glycemic medications reports P<0.001. The original assessment records adjusted ANCOVA, but the adjusted coefficient, SE and CI were not reported. formal_adjusted_CI is null, not 0. It is not replaced by an unadjusted descriptive difference. - Why unverified: The formal analysis type, adjustment variables and P reported as an inequality were linked. The formal effect magnitude and interval were not verified. - Reason for missing information: The adjusted coefficient, SE, CI, exact analysis denominators and model output are unverified. - Required materials and conditions: ANCOVA specifications, adjusted coefficient, SE, CI, denominators and results table - Materials to obtain first: ANCOVA specifications, adjusted coefficient, SE, CI, denominators and results table - Further research: Compare formal model output and the results table to verify the formal effect of interest, interval and denominators. - Conditions for verification: Link the formal ANCOVA comparison of change, adjustment variables and reported P separately from the unreported coefficient/SE/CI. - Why this condition is needed: Needed to avoid establishing effect magnitude or precision from statistical significance alone. - Application exceptions: P<0.001 is not an exact P value; no adjusted CI or standardized effect is newly back-calculated. - Remaining uncertainty: The formal analysis type, adjustment variables and P reported as an inequality were linked. The formal effect magnitude and interval were not verified. - Referenced methods: M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations for each question are internally designed; M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; adaptations for each study design are internally designed; M08 §8.2.2, M15 §15.3.1; internal application; M15 §15.3.1–15.3.3; internal application — An internally developed, item-specific adaptation for Adjusted effect and interval. No official methodological tool was applied or certification performed. - Related sources: S01 ### N24 · Have the baseline SD values of 9.2 and 9.7 been silently harmonized? Verification status: Conflicting information Reading scope: Summary read: the actual locations and values in the current retained summary for case 3111 were read. Access to external or older separate source materials was not attempted in this exercise; they were neither acquired nor read - Current findings: The manuscript preserves the baseline SD conflict of 9.2 versus 9.7 in the original table, without harmonizing the values as though resolved. The exact table cell, group attribution or correction status of each value is not newly established from the current stored summary alone. - Why unverified: The manuscript explicitly records inconsistent values for the same baseline SD. The conflict remains unresolved because the original PDF/table was not reopened in this exercise. - Reason for missing information: Exact table cells, group/time-point attribution and correction history are unverified. - Required materials and conditions: Locations of baseline SD in the original Table 4 and text, corrections, and group/time-point specifications - Materials to obtain first: Locations of baseline SD in the original Table 4 and text, corrections, and group/time-point specifications - Further research: Compare the original table, relevant text and correction history for the same group/time point to verify the location and attribution of the SD conflict. - Conditions for verification: Retain the conflict between the two baseline SD values reported in the retained manuscript and their unresolved attribution. - Why this condition is needed: Needed to avoid arbitrarily selecting or correcting conflicting variability values, or using them as established inputs for a CI calculation. - Application exceptions: Preserve only the recorded conflict of 9.2 versus 9.7 without filling in table cells or group attribution absent from the current stored summary. - Remaining uncertainty: The manuscript explicitly records inconsistent values for the same baseline SD. The conflict remains unresolved because the original PDF/table was not reopened in this exercise. - Referenced methods: M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; adaptations for each study design are internally designed; M04 §4.6.3, M15 §15.3.1–15.3.3; the separation of statuses is internally designed — An internally developed, item-specific adaptation for Conflicting baseline SD. No official methodological tool was applied or certification performed. - Related sources: S01 ### N25 · Is there an applicable MCID for painDETECT change in this population? Verification status: Unverified Reading scope: Summary read: the actual locations and values in the current retained summary for case 3111 were read. Access to external or older separate source materials was not attempted in this exercise; they were neither acquired nor read - Current findings: An applicable criterion for clinical importance is unverified. The manuscript did not assign EX solely because an MCID was absent; it separately records the unverified adjusted estimate, SE, CI and analysis denominators. - Why unverified: The clinical importance of the score change in the selected population cannot be established within the current scope. - Reason for missing information: An applicable MCID, scale implementation and formal effect interval are unverified. - Required materials and conditions: Evidence for an MCID applicable to this population, scale version and change estimate - Materials to obtain first: Evidence for an MCID applicable to this population, scale version and change estimate - Further research: Compare evidence on important change in the same population and scale version with the score definition, and interpret it alongside the reported interval. - Conditions for verification: Distinguish a criterion for an important difference applicable to the selected score, population and time point from a diagnostic screening threshold. - Why this condition is needed: Needed to avoid elevating a statistically significant score difference to a clinically important mean analgesic effect. - Application exceptions: Do not turn a screening total-score threshold into an MCID or substitute thresholds from another disease or language. Do not reassess the original EX solely because an MCID is absent. - Remaining uncertainty: The clinical importance of the score change in the selected population cannot be established within the current scope. - Referenced methods: M15 §15.3.1–15.3.3; internal application; M08 Table 8.2.a, M03 §3.2.4; internal application — An internally developed, item-specific adaptation for Clinical importance. No official methodological tool was applied or certification performed. - Related sources: S01, S04 ### N26 · Was the identity of NCT04706377 distinguished from reading its content? Verification status: Partly verified Reading scope: Summary read: the actual locations and values in the current retained summary for case 3111 were read. Access to external or older separate source materials was not attempted in this exercise; they were neither acquired nor read - Current findings: NCT04706377 is the registration number linked to the original trial. Historical access was registration_shell_only; the record states that the initial posting date, amendment history, primary pain-endpoint hierarchy and prespecified analysis plan could not be verified. The registration was not queried in this exercise either. - Why unverified: The registration identity is preserved, but comparison of the registration content and prespecified hierarchy remains incomplete. - Reason for missing information: The initial posting, amendment history, readable endpoint hierarchy and protocol/SAP are unverified. - Required materials and conditions: Original registration record, initial posting, amendment history and outcome hierarchy - Materials to obtain first: Original registration record, initial posting, amendment history and outcome hierarchy - Further research: Compare the initial registration and amendment history with outcome reporting to assess temporal order, the selected endpoint and reasons for changes. - Conditions for verification: Distinguish linking a registration number from obtaining the initial posting, amendment history and readable endpoint hierarchy. - Why this condition is needed: Needed to avoid turning the existence of a registration number into verification of a prespecified primary (1st) endpoint or registration timing. - Application exceptions: Do not present historical access classified as registration_shell_only as reading the full registration or as confirmation that the trial was unregistered. - Remaining uncertainty: The registration identity is preserved, but comparison of the registration content and prespecified hierarchy remains incomplete. - Referenced methods: M04 §4.5–4.6 principles for collecting/selecting material; the separation of access from reading and the hyperlink contract are internally designed; M08 Table 8.2.a, M04 §4.6.3; internal application — An internally developed, item-specific adaptation for Registration history. No official methodological tool was applied or certification performed. - Related sources: S01, S03 ### N27 · Were the protocol and SAP compared with the selection of actual results? Verification status: Unverified Reading scope: Summary read: the actual locations and values in the current retained summary for case 3111 were read. Access to external or older separate source materials was not attempted in this exercise; they were neither acquired nor read - Current findings: The protocol, SAP and registered endpoint hierarchy are unverified. The original assessment describes multiple endpoints, prespecified hierarchy and inconsistent diagnostic criteria as separate risks; primary_failed_secondary_positive and coprimary_split in axes are null. - Why unverified: Without a direct comparison of plans and reporting, prespecification, the circumstances of changes and handling of multiple endpoints are not established. - Reason for missing information: The protocol, SAP, handling of multiple endpoints and documentation of reasons for changes are unverified. - Required materials and conditions: Protocol, SAP, prespecified endpoints/analyses/time points, handling of multiple endpoints and reporting - Materials to obtain first: Protocol, SAP, prespecified endpoints/analyses/time points, handling of multiple endpoints and reporting - Further research: Compare the registration, protocol and SAP with all reported endpoints, analyses and time points to assess changes to the plan and reasons for selection. - Conditions for verification: Distinguish unavailable plans and unverified multiple-endpoint handling and prespecified hierarchy from confirmed selective reporting. - Why this condition is needed: Needed to expose the lack of materials for assessing whether only favorable scores were selected. - Application exceptions: Do not treat unavailable materials as confirmation of selective reporting or arbitrarily fill in primary_failed_secondary_positive as true/false. - Remaining uncertainty: Without a direct comparison of plans and reporting, prespecification, the circumstances of changes and handling of multiple endpoints are not established. - Referenced methods: M08 Table 8.2.a, M04 §4.6.3; internal application; M04 §4.6.3, M15 §15.3.1–15.3.3; the separation of statuses is internally designed — An internally developed, item-specific adaptation for Plans and multiple endpoints. No official methodological tool was applied or certification performed. - Related sources: S01, S03 ### N28 · Were nonsignificant results for MNSIE and HbA1c preserved? Verification status: Met Reading scope: Summary read: the actual locations and values in the current retained summary for case 3111 were read. Access to external or older separate source materials was not attempted in this exercise; they were neither acquired nor read - Current findings: The manuscript also preserves the between-group MNSIE P=0.607 and HbA1c P=0.876. Nonsignificance for these two different endpoints is not reinterpreted as direct refutation of painDETECT, equivalence or an effect of 0. - Why unverified: The manuscript's other endpoints, results without a significant difference and attribution boundaries were preserved. Their full analyses and intervals were not verified. - Reason for missing information: Detailed denominators, analyses and intervals for the two endpoints are unverified in the current summary. - Required materials and conditions: All reported endpoints, denominators, time points and analyses, including favorable results and results without a significant difference - Materials to obtain first: All reported endpoints, denominators, time points and analyses, including favorable results and results without a significant difference - Further research: Compare each endpoint, denominator and analysis in the complete results table to assess how favorable results and those without a significant difference relate to the selected score. - Conditions for verification: Attribute P=0.607 and P=0.876 to their other endpoints separately from the selected painDETECT outcome. - Why this condition is needed: Other endpoints without a significant difference must be preserved alongside favorable scores, rather than retaining only favorable scores. - Application exceptions: Do not reinterpret nonsignificance as an effect of 0, equivalence or direct refutation of the painDETECT result. - Remaining uncertainty: The manuscript's other endpoints, results without a significant difference and attribution boundaries were preserved. Their full analyses and intervals were not verified. - Referenced methods: M04 §4.6.3, M15 §15.3.1–15.3.3; the separation of statuses is internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations for each question are internally designed — An internally developed, item-specific adaptation for Results without a significant difference. No official methodological tool was applied or certification performed. - Related sources: S01 ### N29 · Are S01, S02 and S03 being counted as three replications? Verification status: Met Reading scope: Summary read: the actual locations and values in the current retained summary for case 3111 were read. Access to external or older separate source materials was not attempted in this exercise; they were neither acquired nor read - Current findings: S01's DOI 10.3390/nu13020395, PMID 33513879 and PMCID PMC7912007 correspond to the S02 bibliographic record, and NCT04706377 is linked to S03. The original trial, index and registration records in F01 are not counted as 3 independent replications. - Why unverified: The retained identifiers and registration linkage for the same original trial were verified. The full registration and all related reports were not exhaustively checked in this exercise. - Reason for missing information: Exhaustive comparison of all related reports and study families, and the total number of unique participants, remain undetermined. - Required materials and conditions: DOI, PMID, PMCID, registration number and report-family linkage - Materials to obtain first: DOI, PMID, PMCID, registration number and report-family linkage - Further research: Compare identifiers, trial numbers and original-report identities to link reports belonging to the same trial family. - Conditions for verification: Link the original trial, NLM bibliographic record and registration number within F01, distinguishing them from independent replication. - Why this condition is needed: Needed to avoid converting the number of article, bibliographic and registration reports into a count of unique trials. - Application exceptions: Do not delete bibliographic/registration records because they lack separate results, or add linked records as new independent trials. - Remaining uncertainty: The retained identifiers and registration linkage for the same original trial were verified. The full registration and all related reports were not exhaustively checked in this exercise. - Referenced methods: M04 §4.6.1–4.6.2 distinction between studies and reports; cohort/outcome linkage is an internal application; M04 §4.6.1–4.6.2, M15 §15.3.1; internal application — An internally developed, item-specific adaptation for Same-trial family. No official methodological tool was applied or certification performed. - Related sources: S01, S02, S03 ### N30 · Are improvement and the absence of a significant nerve-conduction difference in S05 being read as replication of the same question? Verification status: Partly verified Reading scope: Summary read: the actual locations and values in the current retained summary for case 3111 were read. Access to external or older separate source materials was not attempted in this exercise; they were neither acquired nor read - Current findings: The 1992 abstract for F02 reported improvement in somatic and autonomic symptoms, but stated that nerve-conduction changes at 4 months were not significant. Exact between-group painDETECT values, the same population, dose and relevant denominators are unverified; it was not counted as a direct replication. - Why unverified: Favorable symptom results, nerve-conduction results without a significant difference and the reasons for exclusion were preserved together. Replication within the exact boundaries was not verified. - Reason for missing information: The same population, dose, scale, between-group scores, denominators and original full text are unverified. - Required materials and conditions: S05 original abstract, population/dose/scale, denominators, duration and results - Materials to obtain first: S05 original abstract, population/dose/scale, denominators, duration and results - Further research: Compare population, dose, measurements and denominators in the original abstract and full text to distinguish direct replication from adjacent symptom results. - Conditions for verification: Record F02's symptom improvement and nonsignificant nerve-conduction result at 4 months alongside the unverified selected score, population and dose. - Why this condition is needed: Needed to avoid creating an exact painDETECT replication from favorable related symptom results alone. - Application exceptions: Do not substitute nonsignificant nerve-conduction results at 4 months for no effect on the selected 12-month painDETECT outcome. - Remaining uncertainty: Favorable symptom results, nerve-conduction results without a significant difference and the reasons for exclusion were preserved together. Replication within the exact boundaries was not verified. - Referenced methods: M04 §4.6.1–4.6.2 distinction between studies and reports; cohort/outcome linkage is an internal application; M04 §4.6.3, M15 §15.3.1–15.3.3; the separation of statuses is internally designed; M04 §4.6.1–4.6.2, M15 §15.3.1; internal application — An internally developed, item-specific adaptation for Adjacent 1992 trial. No official methodological tool was applied or certification performed. - Related sources: S05 ### N31 · Is a comparison of 1000 versus 2000 µg a placebo-controlled replication? Verification status: Partly verified Reading scope: Summary read: the actual locations and values in the current retained summary for case 3111 were read. Access to external or older separate source materials was not attempted in this exercise; they were neither acquired nor read - Current findings: F03's 2026 title compares oral B12 at 1000 µg versus 2000 µg. It has no control without supplementation, and the record states that direct numerical pain results could not be verified from the accessed metadata. It was not counted as a direct replication of the placebo comparison. - Why unverified: The active-dose comparison's identity and reason for exclusion as a direct replication were preserved. Exact pain outcomes, population and chemical form were not verified. - Reason for missing information: The original full text, numerical pain results, denominators and exact correspondence of chemical form/population are unverified. - Required materials and conditions: S06 population, chemical form, active doses, endpoints, denominators and full results - Materials to obtain first: S06 population, chemical form, active doses, endpoints, denominators and full results - Further research: Compare the original trial's population, chemical form, doses, comparator and endpoints, and assess dose comparison as a separate question. - Conditions for verification: Distinguish F03's comparison of two active doses from a placebo comparison without supplementation, without filling in unverified pain values. - Why this condition is needed: A comparison of two active doses differs from the efficacy question of added B12 versus no supplementation. - Application exceptions: Do not automatically establish that oral B12 in the title means the exact methylcobalamin form, the same painDETECT endpoint or the same population. - Remaining uncertainty: The active-dose comparison's identity and reason for exclusion as a direct replication were preserved. Exact pain outcomes, population and chemical form were not verified. - Referenced methods: M04 §4.6.1–4.6.2 distinction between studies and reports; cohort/outcome linkage is an internal application; M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed; M04 §4.6.1–4.6.2, M15 §15.3.1; internal application; M03 §3.2.1–3.2.4; details on dose, duration and effect modification are internally designed — An internally developed, item-specific adaptation for 2026 active-dose comparison. No official methodological tool was applied or certification performed. - Related sources: S06 ### N32 · Are S11 and S12 being counted as new independent replications? Verification status: Partly verified Reading scope: Summary read: the actual locations and values in the current retained summary for case 3111 were read. Access to external or older separate source materials was not attempted in this exercise; they were neither acquired nor read - Current findings: S11 is retained as a discovery excerpt with failed full-text access, and S12 as discovery metadata for a review/meta-analysis of mixed B-vitamin types, routes and formulations. Neither is counted toward direct effects; no included-study table or exact replication count is newly created here. - Why unverified: Discovery identities and historical access limitations were linked. Comparison of included studies and families addressing the same question remains incomplete. - Reason for missing information: Review full texts, included-study tables, original-report families and results within the same boundaries are unverified. - Required materials and conditions: Reviews' included-study tables, original-trial identities, chemical forms/routes/endpoints and duplicate-report linkage - Materials to obtain first: Reviews' included-study tables, original-trial identities, chemical forms/routes/endpoints and duplicate-report linkage - Further research: Link the trials included in reviews to original reports, then individually compare family overlap, differences in conditions and unverified results. - Conditions for verification: Distinguish review identities used for discovery from comparison of the actual inclusion and results of independent original trials. - Why this condition is needed: Needed to avoid adding discovery citations to the number of independent trials addressing the same question. - Application exceptions: Do not use reviews of mixed B-vitamin types, routes and formulations as direct results for a single-ingredient methylcobalamin painDETECT comparison. - Remaining uncertainty: Discovery identities and historical access limitations were linked. Comparison of included studies and families addressing the same question remains incomplete. - Referenced methods: M04 §4.6.1–4.6.2 distinction between studies and reports; cohort/outcome linkage is an internal application; M04 §4.5, §4.6.3; limits on the present conversion of material reflect the user-defined scope and internal design; M04 §4.6.1–4.6.2, M15 §15.3.1; internal application — An internally developed, item-specific adaptation for Reviews and discovery leads. No official methodological tool was applied or certification performed. - Related sources: S11, S12 ### N33 · Were product supply and no external funding reinterpreted as independent funding? Verification status: Partly verified Reading scope: Summary read: the actual locations and values in the current retained summary for case 3111 were read. Access to external or older separate source materials was not attempted in this exercise; they were neither acquired nor read - Current findings: The original trial retains declarations of no external research funding, in-kind company supply of product and placebo, no company involvement and no conflicts of interest. The original assessment's I1 is not changed to public independent funding I2 or manufacturer-only I0. - Why unverified: The reported declarations were linked, but no verification by an independent institution or new exhaustive review of interests was performed. - Reason for missing information: Detailed contracts, author/institutional relationships and independent verification are unverified. - Required materials and conditions: Research funding, product/placebo supply, company role, COI and institutional/author declarations - Materials to obtain first: Research funding, product/placebo supply, company role, COI and institutional/author declarations - Further research: Compare funding, supply, company roles and author declarations report by report, recording the scope of verification and omissions. - Conditions for verification: Preserve separately the scope of declarations of no external research funding, company product/placebo supply, no involvement and no COI. - Why this condition is needed: Needed to avoid confusing in-kind product supply with funding and independent replication. - Application exceptions: Do not use company supply as an automatic reason for exclusion or infer public independent funding I2 or manufacturer-only I0 from no external funding. - Remaining uncertainty: The reported declarations were linked, but no verification by an independent institution or new exhaustive review of interests was performed. - Referenced methods: Chamgap's own criteria for independence and attribution. The official methods sections used in this pilot do not endorse all of these detailed items — An internally developed, item-specific adaptation for Funding and independence. No official methodological tool was applied or certification performed. - Related sources: S01 ### N34 · Is nonreporting of suspected B12-related AEs being read as 0 AEs of any kind? Verification status: Partly verified Reading scope: Summary read: the actual locations and values in the current retained summary for case 3111 were read. Access to external or older separate source materials was not attempted in this exercise; they were neither acquired nor read - Current findings: The manuscript retains the report that no suspected B12-related adverse reactions were reported in the limited trial. Group-specific denominators for all AEs/SAEs, collection methods, discontinuations and safety over the long term or in special populations are unverified. This is not reinterpreted as 0 events of any kind or as harm incidence. - Why unverified: The narrow scope of the original harms report was preserved. The complete event and discontinuation records, denominators and collection system were not verified. - Reason for missing information: All AEs, SAEs, discontinuations, collection methods, events/people and denominators by group, and long-term/special-population data, are unverified. - Required materials and conditions: All AEs, SAEs, relatedness, discontinuations, collection methods, events/people and denominators/duration by group - Materials to obtain first: All AEs, SAEs, relatedness, discontinuations, collection methods, events/people and denominators/duration by group - Further research: Compare original safety tables and collection, relatedness and discontinuation records by group to distinguish people, events, duration and unreported information. - Conditions for verification: Distinguish the report that no suspected B12-related adverse reactions were observed from all AEs/SAEs, discontinuations, denominators and the scope of collection. - Why this condition is needed: Needed to avoid turning limited reporting of relatedness into absence of all events or verified safety. - Application exceptions: Do not substitute 0 AEs, SAEs or discontinuations for the report that everyone completed the trial, or newly calculate event rates. - Remaining uncertainty: The narrow scope of the original harms report was preserved. The complete event and discontinuation records, denominators and collection system were not verified. - Referenced methods: M19 §19.1.2–19.2.4; internal application; M19 §19.1.2–19.2.4; detailed differentiation is internally designed; M19 §19.1.2–19.2.4, M04 §4.6.3; internal application — An internally developed, item-specific adaptation for Trial reporting of harms. No official methodological tool was applied or certification performed. - Related sources: S01, S07, S08, S09 ### N35 · Is the safety context of metformin and low B12 an analgesic effect? Verification status: Met Reading scope: Summary read: the actual locations and values in the current retained summary for case 3111 were read. Access to external or older separate source materials was not attempted in this exercise; they were neither acquired nor read - Current findings: S07 is an MHRA safety document concerning the association between metformin and low B12 and risk monitoring. The retained manuscript uses it as population and safety context, not as evidence for a methylcobalamin pain effect or individual medication changes. - Why unverified: The retained role of the official document and the boundaries excluding efficacy claims and personal instructions were verified. The official source text was not read in this exercise. - Reason for missing information: Changes to the current official document and applicability to individuals were not checked in this exercise. - Required materials and conditions: Population, scope of recommendations and original location in official document S07 - Materials to obtain first: Population, scope of recommendations and original location in official document S07 - Further research: Compare the official document's exposure, population and recommendations with the original trial question to distinguish safety context from efficacy claims. - Conditions for verification: Distinguish the MHRA risk-monitoring context from efficacy of the selected methylcobalamin intervention and individual medication changes. - Why this condition is needed: Needed to avoid reversing an association between medication and B12 status into an analgesic effect of supplementation. - Application exceptions: Do not use the official monitoring document to justify a methylcobalamin painDETECT effect or an individual change in metformin. - Remaining uncertainty: The retained role of the official document and the boundaries excluding efficacy claims and personal instructions were verified. The official source text was not read in this exercise. - Referenced methods: M03 §3.2.1; detailed population criteria are internally designed; M19 §19.1.2–19.2.4; internal application; Chamgap's own interpretive boundaries. M19 principles are referenced; no official causality assessment tool was applied — An internally developed, item-specific adaptation for Official metformin document. No official methodological tool was applied or certification performed. - Related sources: S07 ### N36 · Has the cobalt warning been repurposed as a methylcobalamin event rate? Verification status: Met Reading scope: Summary read: the actual locations and values in the current retained summary for case 3111 were read. Access to external or older separate source materials was not attempted in this exercise; they were neither acquired nor read - Current findings: The MHRA cobalt-sensitivity notice in S08 explicitly names hydroxocobalamin and cyanocobalamin. This warning was not repurposed as harm incidence in the methylcobalamin trial; warnings for other products and individual safety are distinguished. - Why unverified: The chemical forms explicitly named in the retained notice and limits on transferring it were verified. This does not mean that methylcobalamin has no allergy risk. - Reason for missing information: Direct chemical-form-specific methylcobalamin events, denominators and individual applicability are unverified. - Required materials and conditions: Specified products, chemical forms and scope of sensitivity reactions in official notice S08 - Materials to obtain first: Specified products, chemical forms and scope of sensitivity reactions in official notice S08 - Further research: Compare the notice's specified chemical forms and reactions with the trial formulation and population to assess the scope of the warning's applicability. - Conditions for verification: Preserve the chemical-form and event scope of the warning explicitly naming hydroxocobalamin and cyanocobalamin. - Why this condition is needed: Needed to avoid transferring warnings for other cobalamins to harm incidence in this trial or individual safety. - Application exceptions: Do not turn a cobalt-sensitivity warning into confirmation that methylcobalamin is risk-free, or that causality or frequency of harm is established. - Remaining uncertainty: The chemical forms explicitly named in the retained notice and limits on transferring it were verified. This does not mean that methylcobalamin has no allergy risk. - Referenced methods: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed; M19 §19.1.2–19.2.4; internal application; Chamgap's own interpretive boundaries. M19 principles are referenced; no official causality assessment tool was applied — An internally developed, item-specific adaptation for Warnings for other chemical forms. No official methodological tool was applied or certification performed. - Related sources: S08 ### N37 · Does the ODS statement that no UL is established mean unlimited safety? Verification status: Partly verified Reading scope: Summary read: the actual locations and values in the current retained summary for case 3111 were read. Access to external or older separate source materials was not attempted in this exercise; they were neither acquired nor read - Current findings: S09 is a record reusing a citation/safety excerpt from prior record 110, with original verified_date=2026-07-07. NIH's statement that no UL is established is not a guarantee of unlimited safety. The ODS original and prior record 110 file were not read in this exercise; that record was checked only in the current case 3111 summary. - Why unverified: The inherited description and historical source were linked. The original ODS text, original bytes of prior record 110 and long-term/special-population safety were not compared in this exercise. - Reason for missing information: The current ODS original, original bytes of the prior record 110 excerpt and long-term/special-population harms data are unverified. - Required materials and conditions: Original S09 ODS text, actual content/review history of the excerpt from prior record 110, and long-term/special-population safety data - Materials to obtain first: Original S09 ODS text, actual content/review history of the excerpt from prior record 110, and long-term/special-population safety data - Further research: Separately compare the original location of the ODS description, the prior excerpt and long-term/special-population harms data to assess how absence of an upper limit can be interpreted. - Conditions for verification: Distinguish the inherited UL description and source-material review date from prior record 110 from actual reading in the current exercise. - Why this condition is needed: Needed because absence of a UL differs from a guarantee of safety at high doses, over the long term or in all populations. - Application exceptions: Do not present the review date 2026-07-07 from prior record 110 as the actual access date of S09 or the date of reading ODS in this exercise. - Remaining uncertainty: The inherited description and historical source were linked. The original ODS text, original bytes of prior record 110 and long-term/special-population safety were not compared in this exercise. - Referenced methods: M04 §4.5–4.6 principles for collecting/selecting material; the separation of access from reading and the hyperlink contract are internally designed; M19 §19.1.2–19.2.4; internal application; Chamgap's own interpretive boundaries. M19 principles are referenced; no official causality assessment tool was applied — An internally developed, item-specific adaptation for UL and reused source. No official methodological tool was applied or certification performed. - Related sources: S09 ### N38 · Does this also answer optimal dose, persistence after stopping and effects in people with normal B12? Verification status: Unverified Reading scope: Summary read: the actual locations and values in the current retained summary for case 3111 were read. Access to external or older separate source materials was not attempted in this exercise; they were neither acquired nor read - Current findings: The selected conditions are 1000 µg/day for 12 months in people with long-term metformin use and low B12. Optimal dose, maintenance after discontinuation and effects in a normal-B12 population are unverified. S06's comparison of different active doses is not automatically used to verify these extensions. - Why unverified: The direct evidence required for extensions beyond the selected scope was not verified. No new mandatory conditions were added to the original score comparison. - Reason for missing information: Direct estimates for optimal dose, post-discontinuation follow-up and normal-B12 populations/subgroups are unverified. - Required materials and conditions: Direct dose comparisons, follow-up after discontinuation and prespecified interaction results for normal-B12 populations/subgroups - Materials to obtain first: Direct dose comparisons, follow-up after discontinuation and prespecified interaction results for normal-B12 populations/subgroups - Further research: Define dose, post-discontinuation follow-up and subgroup questions separately, then assess the corresponding direct comparisons and interaction results. - Conditions for verification: Distinguish 1000 µg/day for 12 months in the selected low-B12 population from extensions concerning dose, post-discontinuation follow-up and normal B12. - Why this condition is needed: Needed to avoid extending the main effect to an optimal dose, permanent effect or effects at all B12 levels. - Application exceptions: Do not make every dose, discontinuation or normal-B12 study mandatory for the narrow original question. Do not determine an optimal dose solely from S06's active-dose title. - Remaining uncertainty: The direct evidence required for extensions beyond the selected scope was not verified. No new mandatory conditions were added to the original score comparison. - Referenced methods: M03 §3.2.1–3.2.4; details on dose, duration and effect modification are internally designed; M03 §3.2.1; detailed population criteria are internally designed — An internally developed, item-specific adaptation for Dose, persistence and subgroups. No official methodological tool was applied or certification performed. - Related sources: S01, S06 ### N39 · Are NRS, replacement of analgesics and clinical events being required for this score question? Verification status: Not applicable Reading scope: Summary read: the actual locations and values in the current retained summary for case 3111 were read. Access to external or older separate source materials was not attempted in this exercise; they were neither acquired nor read - Current findings: Direct results for mean pain NRS/VAS, replacement of analgesics and clinical events are not imposed as additional mandatory conditions for the currently selected painDETECT score question. Those extended efficacy claims were not verified, and the manuscript does not extend the result to a general analgesic effect. - Why unverified: A requirement to impose studies of other clinical questions as mandatory for the current narrow score comparison does not apply. This does not eliminate unread or unverified material. - Reason for missing information: Direct effects and intervals for mean NRS, medication replacement and clinical events remain unverified as separate questions. - Required materials and conditions: Interpretive boundaries of the selected question and corresponding direct clinical results if the claim is extended - Materials to obtain first: Interpretive boundaries of the selected question and corresponding direct clinical results if the claim is extended - Further research: When extending the question to mean pain, medication replacement or clinical events, define and assess separate populations, endpoints, comparators and direct results. - Conditions for verification: Distinguish the selected painDETECT score itself from separate questions about mean pain NRS, replacement of analgesics and clinical events. - Why this condition is needed: Needed to avoid unconditionally requiring studies of other clinical questions for the narrow score question. - Application exceptions: Does not apply does not mean that other clinical outcomes were verified. Mean pain intensity and replacement of analgesics remain unverified. - Remaining uncertainty: A requirement to impose studies of other clinical questions as mandatory for the current narrow score comparison does not apply. This does not eliminate unread or unverified material. - Referenced methods: M03 §3.1, §3.2.1–3.2.4 principles for clarifying the question; detailed separation rules are internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations for each question are internally designed; M03 §3.2.4; internally defined boundaries for extending the claim — An internally developed, item-specific adaptation for Other clinical questions. No official methodological tool was applied or certification performed. - Related sources: S01, S04 ### N40 · Were the stored summary, historical full-text reading and current unread status distinguished? Verification status: Met Reading scope: Summary read: the actual locations and values in the current retained summary for case 3111 were read. Access to external or older separate source materials was not attempted in this exercise; they were neither acquired nor read - Current findings: What was actually read in this exercise was the Korean text, structure, evidence, citations and historical records in the current case 3111 stored summary. Historical access_level values for the S01 PDF, S04 author-hosted web full text, official/manufacturer documents and other materials are preserved as manuscript records. Access to external originals, the registration, prior record 110, and older ZIP/audit/calculation logs was not attempted in this exercise; they were neither acquired nor read. Report-specific actual access dates are null because the original citations do not provide them. - Why unverified: The distinction between actual summary reading and historical/current access to each material was documented. External source content was not newly verified. - Reason for missing information: Current original bytes of external or older separate source materials, and actual access dates for individual materials, are unverified. - Required materials and conditions: Exact locations in retained summaries, physical material types, historical access, current acquisition/reading and dates - Materials to obtain first: Exact locations in retained summaries, physical material types, historical access, current acquisition/reading and dates - Further research: Record each material's identity, original location, access events and acquisition/reading separately, and distinguish summary links from external links when comparing them. - Conditions for verification: Separate actual reading of the current stored summary from each material's historical access, lack of original bytes and unattempted access in this exercise. - Why this condition is needed: Needed to avoid upgrading full-text access recorded in an original citation to full-text reading in this exercise. - Application exceptions: Leave missing report-specific access dates null. Do not infer access dates from the global verified_date. - Remaining uncertainty: The distinction between actual summary reading and historical/current access to each material was documented. External source content was not newly verified. - Referenced methods: M04 §4.5–4.6 principles for collecting/selecting material; the separation of access from reading and the hyperlink contract are internally designed; M04 §4.5, §4.6.3; limits on the present conversion of material reflect the user-defined scope and internal design — An internally developed, item-specific adaptation for Actual reading. No official methodological tool was applied or certification performed. - Related sources: S01, S02, S03, S04, S05, S06, S07, S08, S09, S10, S11, S12 ### N41 · Is the review of 2026-09-16 being read as a current exhaustive search? Verification status: Partly verified Reading scope: Summary read: the actual locations and values in the current retained summary for case 3111 were read. Access to external or older separate source materials was not attempted in this exercise; they were neither acquired nor read - Current findings: The evidence reference date is 2026-09-16, and the review date for this conversion is 2026-10-05. evidence_status records verification of direct human evidence and eligible comparisons within the historical ChatGPT search scope, but absence_proven is false. The current corrections list is empty; no new search or correction/retraction lookup was performed in this exercise. - Why unverified: The historical search scope and current conversion scope were linked, but no current exhaustive search or correction check was performed. - Reason for missing information: No new search or exhaustive check of current corrections/retractions and unpublished/registered materials was performed. - Required materials and conditions: Historical search scope, list of unverified matters, correction/retraction records and reasons for updates - Materials to obtain first: Historical search scope, list of unverified matters, correction/retraction records and reasons for updates - Further research: During an authorized update, compare the historical search scope with the scope of new materials, and link corrections, retractions and unpublished/registered records to original reports. - Conditions for verification: Distinguish the evidence reference date, the review date for this conversion, the historical search scope and the absence of a new search. - Why this condition is needed: Needed to avoid exaggerating a check of stored materials into a current search of all literature or a guarantee of completeness. - Application exceptions: Do not present the absence of a new search as proof of 0 studies, an effect of 0 or no new corrections. - Remaining uncertainty: The historical search scope and current conversion scope were linked, but no current exhaustive search or correction check was performed. - Referenced methods: M04 §4.5, §4.6.3; limits on the present conversion of material reflect the user-defined scope and internal design; M04 §4.6.3, M15 §15.3.1–15.3.3; the separation of statuses is internally designed — An internally developed, item-specific adaptation for Scope of searches and corrections. No official methodological tool was applied or certification performed. - Related sources: S01, S03, S05, S06, S11, S12 ### N42 · Have C, 46 and the existing EX/CX been turned into verdicts produced by this new table? Verification status: Met Reading scope: Summary read: the actual locations and values in the current retained summary for case 3111 were read. Access to external or older separate source materials was not attempted in this exercise; they were neither acquired nor read - Current findings: The original verdict is C, 46 points, with B/P/R1/I1/EX/B2/CX. The manuscript's reruns of the calculator and scoring table are historical records; they were not rerun in this exercise. formal_adjusted_CI and some auxiliary axis fields are null, not 0. The existing −2.9/−3.8 are historical descriptive values; this table creates no new grade, effect or score. - Why unverified: The original values, the historical nature of the calculations and the meaning of null values were preserved. No clinical reassessment or official methodological certification was performed. - Reason for missing information: Original bytes of the original ZIP/audit/calculation logs were not read in this exercise, and the gaps in the adjusted coefficient and CI remain. - Required materials and conditions: Original grade, score, axes, null values, sources of existing calculations and reasons for unverified information - Materials to obtain first: Original grade, score, axes, null values, sources of existing calculations and reasons for unverified information - Further research: Preserve the original assessment inputs, historical calculations and correction records to distinguish original values from new evidence events, and compare before and after an authorized revision. - Conditions for verification: Preserve the original grade/score, 7 axes, null values and references to existing calculations, distinguishing them from statuses in the unscored evidence-gap table. - Why this condition is needed: Needed to avoid automatically carrying the existing assessment over as new table scores, efficacy probabilities or fulfillment of criteria. - Application exceptions: Do not rerun the original calculator or precedents in this exercise. Link the original C, 46, EX, CX and null values only as historical source values. - Remaining uncertainty: The original values, the historical nature of the calculations and the meaning of null values were preserved. No clinical reassessment or official methodological certification was performed. - Referenced methods: M03 §3.1, §3.2.1–3.2.4 principles for clarifying the question; detailed separation rules are internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations for each question are internally designed; M04 §4.5, §4.6.3; limits on the present conversion of material reflect the user-defined scope and internal design — An internally developed, item-specific adaptation for Original verdict and historical calculations. No official methodological tool was applied or certification performed. - Related sources: ### N43 · Is historical deployment metadata being read as completed publication of this table? Verification status: Partly verified Reading scope: Summary read: the actual locations and values in the current retained summary for case 3111 were read. Access to external or older separate source materials was not attempted in this exercise; they were neither acquired nor read - Current findings: The original first_published_at is null and publication_status is ready_with_uncertainty. The record also contains server_deployed=true, server_write_performed=false and deployed_at=2026-09-16. These different historical metadata statements are not read as completed public release of the current table; original values and the policy of revisions under the same ID/URL are preserved. - Why unverified: The original metadata statements and event boundaries were linked. Actual historical deployment receipts and website publication in this exercise were not verified. - Reason for missing information: Comparison of actual historical deployment events, the initial public-release time and a publication receipt for the current table are unverified. - Required materials and conditions: Original ID, canonical URL, initial-publication/server metadata and revision policy/history - Materials to obtain first: Original ID, canonical URL, initial-publication/server metadata and revision policy/history - Further research: Compare receipts for each publication event and actual public-release times with original metadata and revision history, preserving the full before-and-after content under the same ID/URL. - Conditions for verification: Distinguish events in the existing ID/URL and publication/server metadata from this creation and future website posting. - Why this condition is needed: Needed to avoid using historical metadata statements as evidence of public release in this exercise. - Application exceptions: Do not arbitrarily correct original values such as server_deployed=true, server_write_performed=false and first_published_at=null. For this creation, published is false. - Remaining uncertainty: The original metadata statements and event boundaries were linked. Actual historical deployment receipts and website publication in this exercise were not verified. - Referenced methods: M03 §3.1, §3.2.1–3.2.4 principles for clarifying the question; detailed separation rules are internally designed; M04 §4.5, §4.6.3; limits on the present conversion of material reflect the user-defined scope and internal design — An internally developed, item-specific adaptation for Publication metadata and updates. No official methodological tool was applied or certification performed. - Related sources: ## Evidence and sources ### S01 Didangelos et al. 2021. Vitamin B12 Supplementation in Diabetic Neuropathy: A 1-Year, Randomized, Double-Blind, Placebo-Controlled Trial [Source](https://mdpi-res.com/d_attachment/nutrients/nutrients-13-00395/article_deploy/nutrients-13-00395.pdf) Materials actually read: Retained summary read; access to the external or separate original materials was not attempted in this exercise, and they were neither acquired nor read Findings recorded in the summary: Of 90 participants, 44 were allocated to methylcobalamin and 46 to placebo, and all reportedly completed the trial. painDETECT scores were 18.4→17.1 versus 19.3→20.9; the comparison adjusted for HbA1c and glycemic medications reported P<0.001. The existing simple change contrast of −2.9 points and endpoint difference of −3.8 points are unadjusted descriptive values; the adjusted coefficient, SE, CI and endpoint-specific denominators are unverified. MNSIE P=0.607, HbA1c P=0.876 and the baseline SD conflict of 9.2/9.7 are also preserved. Record level: A summary based on reading actual results/attribution and the limits of retained detail in the current case 3111 retained summary. It is not a reading of the original document in this exercise or a new result. Independent replication: The original trial, reports/registration of the same trial, scale, official/manufacturer sources, discovery reviews and adjacent F02/F03 were distinguished. No new unique-trial count was generated automatically. | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Full article text in PDF | Unverified (only retained historical access is linked; no lookup in this exercise) | Not attempted in this exercise | Not read | The existence of a link/bibliographic record is separate from actual acquisition, reading and suitability for the selected question. | ### S02 Didangelos et al. — NLM bibliographic record [Source](https://pubmed.ncbi.nlm.nih.gov/33513879/) Materials actually read: Retained summary read; access to the external or separate original materials was not attempted in this exercise, and they were neither acquired nor read Findings recorded in the summary: This NLM record corresponds to S01 through DOI 10.3390/nu13020395, PMID 33513879 and PMCID PMC7912007. As a discovery source, it was not counted toward direct effects, and this stored summary contains no separate detailed results specific to S02. Record level: A summary based on reading actual results/attribution and the limits of retained detail in the current case 3111 retained summary. It is not a reading of the original document in this exercise or a new result. Independent replication: The original trial, reports/registration of the same trial, scale, official/manufacturer sources, discovery reviews and adjacent F02/F03 were distinguished. No new unique-trial count was generated automatically. | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | PubMed bibliographic record and abstract | Unverified (only retained historical access is linked; no lookup in this exercise) | Not attempted in this exercise | Not read | The existence of a link/bibliographic record is separate from actual acquisition, reading and suitability for the selected question. | ### S03 ClinicalTrials.gov NCT04706377 [Source](https://clinicaltrials.gov/study/NCT04706377) Materials actually read: Retained summary read; access to the external or separate original materials was not attempted in this exercise, and they were neither acquired nor read Findings recorded in the summary: Registration number NCT04706377 was linked. Historical registration_shell_only access and the unverified initial posting, amendment history, pain-endpoint hierarchy and protocol/SAP are retained. Registration identity is not an independent replication or a completed result. Record level: A summary based on reading actual results/attribution and the limits of retained detail in the current case 3111 retained summary. It is not a reading of the original document in this exercise or a new result. Independent replication: The original trial, reports/registration of the same trial, scale, official/manufacturer sources, discovery reviews and adjacent F02/F03 were distinguished. No new unique-trial count was generated automatically. | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Full web clinical-trial registration record | Unverified (only retained historical access is linked; no lookup in this exercise) | Not attempted in this exercise | Not read | The existence of a link/bibliographic record is separate from actual acquisition, reading and suitability for the selected question. | ### S04 Freynhagen et al. 2006. painDETECT: a new screening questionnaire to detect neuropathic components in patients with back pain [Source](https://www.researchgate.net/publication/6771902_Freynhagen_R_Baron_R_Gockel_U_Tolle_TpainDETECT_a_new_screening_questionnaire_to_detect_neuropathic_components_in_patients_with_back_pain_Curr_Med_Res_Opin_22_1911-1920) Materials actually read: Retained summary read; access to the external or separate original materials was not attempted in this exercise, and they were neither acquired nor read Findings recorded in the summary: The original paper-form painDETECT total score has a range of −1–38 and sums sensory qualities, pain course and radiation. Items recording pain intensity are not included in the total score. The trial's exact language, version, recall period and MCID remain separately unverified. Historical rejection of access to the publisher PDF and reading of the author-hosted web full text were not actions performed in this exercise. Record level: A summary based on reading actual results/attribution and the limits of retained detail in the current case 3111 retained summary. It is not a reading of the original document in this exercise or a new result. Independent replication: The original trial, reports/registration of the same trial, scale, official/manufacturer sources, discovery reviews and adjacent F02/F03 were distinguished. No new unique-trial count was generated automatically. | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Full original article text on the author's website | Unverified (only retained historical access is linked; no lookup in this exercise) | Not attempted in this exercise | Not read | The existence of a link/bibliographic record is separate from actual acquisition, reading and suitability for the selected question. | | Publisher's full article text in PDF | Unverified (only retained historical access is linked; no lookup in this exercise) | Not attempted in this exercise | Not read | The existence of a link/bibliographic record is separate from actual acquisition, reading and suitability for the selected question. | ### S05 Yaqub, Siddique, Sulimani. 1992. Effects of methylcobalamin on diabetic neuropathy [Source](https://pubmed.ncbi.nlm.nih.gov/1324807/) Materials actually read: Retained summary read; access to the external or separate original materials was not attempted in this exercise, and they were neither acquired nor read Findings recorded in the summary: The 1992 abstract reported improvement in somatic and autonomic symptoms, but stated that nerve-conduction changes at 4 months were not significant. Between-group values for the selected painDETECT score, the same population, dose and relevant denominators are unverified. Record level: A summary based on reading actual results/attribution and the limits of retained detail in the current case 3111 retained summary. It is not a reading of the original document in this exercise or a new result. Independent replication: The original trial, reports/registration of the same trial, scale, official/manufacturer sources, discovery reviews and adjacent F02/F03 were distinguished. No new unique-trial count was generated automatically. | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | PubMed bibliographic record and abstract | Unverified (only retained historical access is linked; no lookup in this exercise) | Not attempted in this exercise | Not read | The existence of a link/bibliographic record is separate from actual acquisition, reading and suitability for the selected question. | ### S06 Mansour et al. 2026. Efficacy of Oral Vitamin B-12 at 1000 micrograms Compared with 2000 micrograms on Neuropathic Outcomes [Source](https://pubmed.ncbi.nlm.nih.gov/41548600/) Materials actually read: Retained summary read; access to the external or separate original materials was not attempted in this exercise, and they were neither acquired nor read Findings recorded in the summary: The 2026 title is an active-dose comparison of oral B12 at 1000 µg versus 2000 µg. It has no control without supplementation, and direct numerical pain results could not be verified from the accessed metadata. The original full text, chemical form, exact endpoint and correspondence of the population are not filled in from the title alone. Record level: A summary based on reading actual results/attribution and the limits of retained detail in the current case 3111 retained summary. It is not a reading of the original document in this exercise or a new result. Independent replication: The original trial, reports/registration of the same trial, scale, official/manufacturer sources, discovery reviews and adjacent F02/F03 were distinguished. No new unique-trial count was generated automatically. | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | PubMed bibliographic record and search-result title | Unverified (only retained historical access is linked; no lookup in this exercise) | Not attempted in this exercise | Not read | The existence of a link/bibliographic record is separate from actual acquisition, reading and suitability for the selected question. | | Publisher's full article text | Unverified (only retained historical access is linked; no lookup in this exercise) | Not attempted in this exercise | Not read | The existence of a link/bibliographic record is separate from actual acquisition, reading and suitability for the selected question. | ### S07 MHRA. Metformin and reduced vitamin B12 levels: new advice for monitoring patients at risk [Source](https://www.gov.uk/drug-safety-update/metformin-and-reduced-vitamin-b12-levels-new-advice-for-monitoring-patients-at-risk) Materials actually read: Retained summary read; access to the external or separate original materials was not attempted in this exercise, and they were neither acquired nor read Findings recorded in the summary: This is the MHRA monitoring and risk-factor document dated 2022-06-20. The association between metformin and low B12 provides population and safety context; it is not used as evidence for a methylcobalamin pain effect or individual medication changes. Record level: A summary based on reading actual results/attribution and the limits of retained detail in the current case 3111 retained summary. It is not a reading of the original document in this exercise or a new result. Independent replication: The original trial, reports/registration of the same trial, scale, official/manufacturer sources, discovery reviews and adjacent F02/F03 were distinguished. No new unique-trial count was generated automatically. | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Full official safety notice on the web | Unverified (only retained historical access is linked; no lookup in this exercise) | Not attempted in this exercise | Not read | The existence of a link/bibliographic record is separate from actual acquisition, reading and suitability for the selected question. | ### S08 MHRA. Vitamin B12 (hydroxocobalamin, cyanocobalamin): cobalt sensitivity reactions [Source](https://www.gov.uk/drug-safety-update/vitamin-b12-hydroxocobalamin-cyanocobalamin-advise-patients-with-known-cobalt-allergy-to-be-vigilant-for-sensitivity-reactions) Materials actually read: Retained summary read; access to the external or separate original materials was not attempted in this exercise, and they were neither acquired nor read Findings recorded in the summary: The MHRA cobalt-sensitivity notice dated 2023-12-18 explicitly names hydroxocobalamin and cyanocobalamin. It is not repurposed as harm incidence in the methylcobalamin trial or as individual safety. Record level: A summary based on reading actual results/attribution and the limits of retained detail in the current case 3111 retained summary. It is not a reading of the original document in this exercise or a new result. Independent replication: The original trial, reports/registration of the same trial, scale, official/manufacturer sources, discovery reviews and adjacent F02/F03 were distinguished. No new unique-trial count was generated automatically. | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Full official safety notice on the web | Unverified (only retained historical access is linked; no lookup in this exercise) | Not attempted in this exercise | Not read | The existence of a link/bibliographic record is separate from actual acquisition, reading and suitability for the selected question. | ### S09 NIH ODS. Vitamin B12: Fact Sheet for Health Professionals — supplied record 110 citation [Source](https://ods.od.nih.gov/factsheets/VitaminB12-HealthProfessional/) Materials actually read: Retained summary read; access to the external or separate original materials was not attempted in this exercise, and they were neither acquired nor read Findings recorded in the summary: This is NIH ODS's description that no UL is established, inherited from citations/6 and a safety excerpt in prior record 110. The original verified_date=2026-07-07 is not an access date. The statement that no upper limit is established is not reinterpreted as unlimited safety of long-term high doses or in all special populations. Prior record 110 and the external ODS original were not read in this exercise. Record level: A summary based on reading actual results/attribution and the limits of retained detail in the current case 3111 retained summary. It is not a reading of the original document in this exercise or a new result. Independent replication: The original trial, reports/registration of the same trial, scale, official/manufacturer sources, discovery reviews and adjacent F02/F03 were distinguished. No new unique-trial count was generated automatically. | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Full fact sheet on the web | Unverified (only retained historical access is linked; no lookup in this exercise) | Not attempted in this exercise | Not read | The existence of a link/bibliographic record is separate from actual acquisition, reading and suitability for the selected question. | | Excerpted citation from the stored summary of prior record 110 | Unverified (only retained historical access is linked; no lookup in this exercise) | Not attempted in this exercise | Not read | The existence of a link/bibliographic record is separate from actual acquisition, reading and suitability for the selected question. | ### S10 UNI-PHARMA. B12 fix product and food-supplement catalogue [Source](https://www.uni-pharma.gr/en/nonprescriptive/b12-fix/) Materials actually read: Retained summary read; access to the external or separate original materials was not attempted in this exercise, and they were neither acquired nor read Findings recorded in the summary: The conflict between 1000 µg/1000 mg labeling on the current manufacturer page is preserved as unresolved. The trial dose is 1000 µg/day from S01; the current product page does not establish the historical trial batch. Record level: A summary based on reading actual results/attribution and the limits of retained detail in the current case 3111 retained summary. It is not a reading of the original document in this exercise or a new result. Independent replication: The original trial, reports/registration of the same trial, scale, official/manufacturer sources, discovery reviews and adjacent F02/F03 were distinguished. No new unique-trial count was generated automatically. | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Full manufacturer's product description on the web | Unverified (only retained historical access is linked; no lookup in this exercise) | Not attempted in this exercise | Not read | The existence of a link/bibliographic record is separate from actual acquisition, reading and suitability for the selected question. | | Manufacturer's food-supplement catalogue (file format unverified) | Unverified (only retained historical access is linked; no lookup in this exercise) | Not attempted in this exercise | Not read | The existence of a link/bibliographic record is separate from actual acquisition, reading and suitability for the selected question. | ### S11 Jayabalan et al. 2016. Vitamin B supplementation for diabetic peripheral neuropathy [Source](https://www.smj.org.sg/article/vitamin-b-supplementation-diabetic-peripheral-neuropathy) Materials actually read: Retained summary read; access to the external or separate original materials was not attempted in this exercise, and they were neither acquired nor read Findings recorded in the summary: A discovery excerpt from the related 2016 review and failure to access its full text directly at that time were recorded. The current stored summary lacks detailed included studies and results; exact independent replications and effect values are not filled in. Record level: A summary based on reading actual results/attribution and the limits of retained detail in the current case 3111 retained summary. It is not a reading of the original document in this exercise or a new result. Independent replication: The original trial, reports/registration of the same trial, scale, official/manufacturer sources, discovery reviews and adjacent F02/F03 were distinguished. No new unique-trial count was generated automatically. | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Full review article text | Unverified (only retained historical access is linked; no lookup in this exercise) | Not attempted in this exercise | Not read | The existence of a link/bibliographic record is separate from actual acquisition, reading and suitability for the selected question. | ### S12 Mandra et al. 2026. Vitamin B Supplementation for Diabetic Peripheral Neuropathy: A Review and Meta-Analysis [Source](https://www.mdpi.com/2077-0383/15/13/5156) Materials actually read: Retained summary read; access to the external or separate original materials was not attempted in this exercise, and they were neither acquired nor read Findings recorded in the summary: The historical verification locations for the 2026 review/meta-analysis are the publisher's search results and an abstract reproduction including the authors' references. It concerns mixed B-vitamin types, routes and formulations; the current stored summary lacks a detailed included-study table and values for the selected score. No direct replications are added. Record level: A summary based on reading actual results/attribution and the limits of retained detail in the current case 3111 retained summary. It is not a reading of the original document in this exercise or a new result. Independent replication: The original trial, reports/registration of the same trial, scale, official/manufacturer sources, discovery reviews and adjacent F02/F03 were distinguished. No new unique-trial count was generated automatically. | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Full review article text | Unverified (only retained historical access is linked; no lookup in this exercise) | Not attempted in this exercise | Not read | The existence of a link/bibliographic record is separate from actual acquisition, reading and suitability for the selected question. | ## 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 criteria and reasons for changes, and distinguish variations in the intervention. · Reuse of actual bytes/SHA and historical principles from the retained methods HTML copy for case 1585. No new reading of the full methods text, official application or certification was performed in this exercise. - 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 and link studies and reports, and do not omit a study solely because its outcomes are not reported. · Reuse of actual bytes/SHA and historical principles from the retained methods HTML copy for case 1585. No new reading of the full methods text, official application or certification was performed in this exercise. - 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 · Hold the outcome and effect of interest fixed, then assess randomization, deviations, missing data, measurement and selective reporting. · Reuse of actual bytes/SHA and historical principles from the retained methods HTML copy for case 1585. No new reading of the full methods text, official application or certification was performed in this exercise. - 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. · Reuse of actual bytes/SHA and historical principles from the retained methods HTML copy for case 1585. No new reading of the full methods text, official application or certification was performed in this exercise. - 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 · Questions about harms may require designs, populations and follow-up different from efficacy questions. Case reports do not establish incidence. · Reuse of actual bytes/SHA and historical principles from the retained methods HTML copy for case 1585. No new reading of the full methods text, official application or certification was performed in this exercise. ## What the statuses mean - Met: The criterion's identity, attribution within retained materials and interpretive boundaries were verified. This is not confirmation of clinical efficacy/safety or official certification. - Partly verified: Some facts were linked within the currently retained material, but further dimensions of evidence or comparisons remain outstanding. - Unverified: The material read lacks necessary values, criteria or source materials. This does not mean a count or value of 0 for studies, effects or events, or incomplete review in preparing the table. - Conflicting information: The current retained manuscript explicitly states a discrepancy for the same item. The exact scope is preserved without selecting or correcting an original value. - Not applicable: A requirement to impose other extension studies as mandatory for the current narrow score question does not apply. This does not verify other effects or replace an unread status. - Does not apply: A display alias for Not applicable. The original criterion/status is preserved as Not applicable. - Not read: The relevant external or older separate source material was not directly read in this exercise. This is separate from actual reading of the retained summary. - Review incomplete: Actual review of individual criteria/observations for preparation of the table remains outstanding. This is distinct from unverified source information. ## Change history 2026-11-05 · Public page/materials 1.0. The public-facing display and data were prepared from the existing 43 items. No new clinical search, change to verification statuses or scoring was performed. ## Material-specific source addresses - [S01-M1 · Full article text in PDF](https://mdpi-res.com/d_attachment/nutrients/nutrients-13-00395/article_deploy/nutrients-13-00395.pdf) - [S02-M1 · PubMed bibliographic record and abstract](https://pubmed.ncbi.nlm.nih.gov/33513879/) - [S03-M1 · Full web clinical-trial registration record](https://clinicaltrials.gov/study/NCT04706377) - [S04-M1 · Full original article text on the author's website](https://www.researchgate.net/publication/6771902_Freynhagen_R_Baron_R_Gockel_U_Tolle_TpainDETECT_a_new_screening_questionnaire_to_detect_neuropathic_components_in_patients_with_back_pain_Curr_Med_Res_Opin_22_1911-1920) - S04-M2 · Publisher's full article text in PDF: Material URL unverified; external material unread. - [S05-M1 · PubMed bibliographic record and abstract](https://pubmed.ncbi.nlm.nih.gov/1324807/) - [S06-M1 · PubMed bibliographic record and search-result title](https://pubmed.ncbi.nlm.nih.gov/41548600/) - [S06-M2 · Publisher's full article text](https://doi.org/10.1016/j.tjnut.2026.101368) - [S07-M1 · Full official safety notice on the web](https://www.gov.uk/drug-safety-update/metformin-and-reduced-vitamin-b12-levels-new-advice-for-monitoring-patients-at-risk) - [S08-M1 · Full official safety notice on the web](https://www.gov.uk/drug-safety-update/vitamin-b12-hydroxocobalamin-cyanocobalamin-advise-patients-with-known-cobalt-allergy-to-be-vigilant-for-sensitivity-reactions) - [S09-M1 · Full fact sheet on the web](https://ods.od.nih.gov/factsheets/VitaminB12-HealthProfessional/) - S09-M2 · Excerpted citation from the stored summary of prior record 110: Material URL unverified; external material unread. - [S10-M1 · Full manufacturer's product description on the web](https://www.uni-pharma.gr/en/nonprescriptive/b12-fix/) - S10-M2 · Manufacturer's food-supplement catalogue (file format unverified): Material URL unverified; external material unread. - [S11-M1 · Full review article text](https://www.smj.org.sg/article/vitamin-b-supplementation-diabetic-peripheral-neuropathy) - [S12-M1 · Full review article text](https://www.mdpi.com/2077-0383/15/13/5156)