# Nicotinamide riboside (NR; salt and product details unverified) × Improvement of usual gait speed in frail older adults Verdict 3093 · Evidence Check Stored-material review date: 2026-10-05 Original evidence date: 2026-09-15 Review-criteria version: NGM-v3093-NR-FRAIL-USUAL-GAIT-1.0 Public page/material preparation date: 2026-11-01 Clinical papers were not read directly; existing review summaries were checked. No new clinical-literature search was performed. Unverified does not mean that research is absent or that there is no effect. ## Assessment scope - Population: Community-dwelling adults aged 75 or older with a Fried Frailty Phenotype score of 3 or higher; baseline gait speed and nutritional status unverified - Ingredient, formulation and route: Nicotinamide riboside (NR; salt and product details unverified) - Dose: Planned 2000 mg/day; amount per dose, frequency, dose escalation, and basis for salt conversion unverified - Comparator: Placebo (exact composition, matching method, and common care unverified) - Measured outcome: Between-group difference in change in usual gait speed from baseline to week 52 (m/s); the page's primary endpoint, with its actual trial hierarchy and usual-speed protocol unverified - Duration: Planned 52 weeks; actual exposure and follow-up after discontinuation unverified - Questions outside this scope: 6-minute walk distance and WIQ self-reported speed; Maximal speed, SPPB, muscle strength, fatigue, and chair rise; Cognition and NAD biomarkers; Direct transfer of findings from MCI, healthy participants, PAD, and prefrailty; NMN, NAM, niacin, NAD/NADH, tryptophan, and combination products; Optimal dose, persistence after discontinuation, prevention of falls/death, and individual safety ## Checklist items ### N01 · Does the table address only the between-group change in usual gait speed in frail older adults? Verification status: Verified Reading scope: The native summaries and values in the retained manuscript were read. External papers, official documents, and registrations remain unread in the current review. - Current findings: The original claim is improvement of usual gait speed in frail older adults. The single question addresses community-dwelling adults aged 75 or older with a Fried score of 3 or higher, a planned oral NR regimen of 2,000 mg/day for 52 weeks versus placebo, and change in usual speed (m/s). - Why unverified: The claim boundaries are specified in the identity of the retained assessment question. Verification of these boundaries does not verify a completed trial yielding that result or verify efficacy. - Reason for missing information: The claim boundaries are specified in the identity of the retained assessment question. Verification of these boundaries does not verify a completed trial yielding that result or verify efficacy. - Required materials and conditions: Explicit boundaries of the original claim, population, planned oral NR, placebo, and change in usual speed at 52 weeks - Materials to obtain first: Explicit boundaries of the original claim, population, planned oral NR, placebo, and change in usual speed at 52 weeks - Further research: In a new study, specify usual speed as a single outcome of interest and prespecify the population, comparison, measurement time points, and analysis. - Conditions for verification: Link the original /ko/effect to the question identity and identify 6-minute walk distance, muscle strength, cognition, and NAD results as separate questions. - Why this condition is needed: Needed to avoid combining the ingredient's overall functions or different walking endpoints into a single effect. - Application exceptions: If the frailty definition or endpoint actually changes, reassess whether separation is needed while retaining the link to the same original ID. Do not automatically create a new table for another combination. - Remaining uncertainty: The claim boundaries are specified in the identity of the retained assessment question. Verification of these boundaries does not verify a completed trial yielding that result or verify efficacy. - Referenced methods: Principles for clarifying the question in M03 §3.1, §3.2.1–3.2.4; detailed separation rules are internally designed / M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptation is internally designed - Related sources: S01, S02 ### N02 · Are the NR salt, product, dosage form, and batch in the plan verified? Verification status: Unverified Reading scope: The native summaries and values in the retained manuscript were read. External papers, official documents, and registrations remain unread in the current review. - Current findings: The ingredient is retained as NR, but its salt, crystal form, brand, manufacturer, manufacturing source, dosage form, purity, batch, and release form are unverified. NIAGEN information from another trial was not copied into this plan. - Why unverified: The retained identity fields are null or unverified. The molecular name NR alone cannot verify an identical salt, product, or basis for exposure conversion. - Reason for missing information: The retained identity fields are null or unverified. The molecular name NR alone cannot verify an identical salt, product, or basis for exposure conversion. - Required materials and conditions: Documentation of the exact NR salt, product, manufacturer, assayed purity, batch, and release form in NADage - Materials to obtain first: Documentation of the exact NR salt, product, manufacturer, assayed purity, batch, and release form in NADage - Further research: A suitable comparative study records the test product's analytical results, batch, and active ingredient together with the placebo composition to define a reproducible exposure. - Conditions for verification: Verify the identity of the substance actually used in this plan; do not substitute NIAGEN or NR chloride information from another trial. - Why this condition is needed: Needed to avoid directly transferring results and safety findings from different salts, dosage forms, or products. - Application exceptions: If the original source does not clarify the relationship between salt mass and active-moiety amount, retain the reported mg without conversion. - Remaining uncertainty: The retained identity fields are null or unverified. The molecular name NR alone cannot verify an identical salt, product, or basis for exposure conversion. - Referenced methods: M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptation are internally designed - Related sources: S01, S02 ### N03 · Are other active ingredients or exercise packages separated from the NR-versus-placebo comparison? Verification status: Partly verified Reading scope: The native summaries and values in the retained manuscript were read. External papers, official documents, and registrations remain unread in the current review. - Current findings: The question requires an NR-versus-placebo contrast. The principle of not transferring effects from NMN, nicotinamide, niacin, resveratrol, or an exercise package is specified, but full product composition and common care have not been verified. - Why unverified: The contrast to be selected is defined, but the actual plan's full composition and concomitant-intervention rules remain unverified. Requesting a single-component contrast differs from having implemented single-component exposure. - Reason for missing information: The contrast to be selected is defined, but the actual plan's full composition and concomitant-intervention rules remain unverified. Requesting a single-component contrast differs from having implemented single-component exposure. - Required materials and conditions: Full product composition and rules for exercise, rehabilitation, diet, and active-ingredient use in both groups - Materials to obtain first: Full product composition and rules for exercise, rehabilitation, diet, and active-ingredient use in both groups - Further research: Specify standard care in both groups and record differences in exercise or rehabilitation, or design these as a separate factor, to estimate the NR contrast. - Conditions for verification: Verify that the selected contrast is the difference between NR and placebo; do not attribute combined active ingredients or differences in exercise between groups to NR alone. - Why this condition is needed: Needed because differences in other active ingredients or rehabilitation may be mixed with the planned contribution of NR. - Application exceptions: The comparison can be retained even when common care is present if its role in both groups is verified. Do not assume that all concomitant interventions were absent. - Remaining uncertainty: The contrast to be selected is defined, but the actual plan's full composition and concomitant-intervention rules remain unverified. Requesting a single-component contrast differs from having implemented single-component exposure. - Referenced methods: M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptation are internally designed / M03 §3.2.3, M08 §8.2.2–8.2.3; internal application - Related sources: S01, S02 ### N04 · Are the criteria of age 75 or older and Fried score 3 or higher, and the population actually selected, verified? Verification status: Partly verified Reading scope: The native summaries and values in the retained manuscript were read. External papers, official documents, and registrations remain unread in the current review. - Current findings: The official registration index records criteria of community dwelling, age 75 or older, and a Fried Frailty Phenotype score of 3 or higher. The relationship between the investigator page's description of mild-to-moderate frailty, detailed exclusion criteria, and the population actually selected is unverified. - Why unverified: The criteria are a description of the plan verified from a limited official index. The full registration and actual baseline table cannot be verified from the retained summary currently held, so a match with the actual population is not established. - Reason for missing information: The criteria are a description of the plan verified from a limited official index. The full registration and actual baseline table cannot be verified from the retained summary currently held, so a match with the actual population is not established. - Required materials and conditions: Full eligibility criteria, selection flow, Fried components, and actual baseline characteristics table - Materials to obtain first: Full eligibility criteria, selection flow, Fried components, and actual baseline characteristics table - Further research: Record the actual selection criteria, baseline Fried components, and comorbidities, and link the analysis denominator for the frail population of interest. - Conditions for verification: Distinguish the plan's age and frailty criteria read in the official index from whether the population actually recruited and analyzed matches those criteria. - Why this condition is needed: Needed to avoid confusing older age alone, prefrailty, MCI, or PAD with the fixed frailty criteria. - Application exceptions: If data from a mixed population are available, retain the definition of the frail subgroup and its separate results. Do not discard results from other populations or combine them as direct results. - Remaining uncertainty: The criteria are a description of the plan verified from a limited official index. The full registration and actual baseline table cannot be verified from the retained summary currently held, so a match with the actual population is not established. - Referenced methods: M03 §3.2.1; detailed population conditions are internally designed - Related sources: S01, S02 ### N05 · Are baseline usual speed, nutrition, and deficiency status verified? Verification status: Unverified Reading scope: The native summaries and values in the retained manuscript were read. External papers, official documents, and registrations remain unread in the current review. - Current findings: Upper and lower limits for baseline usual gait speed, nutritional status, dietary NR/NAD precursors, and deficiency tests are unverified. The label frailty alone does not establish NR deficiency. - Why unverified: Values related to baseline speed and deficiency in the original assessment question's identity are null. Data are unavailable to distinguish applicability according to the degree of baseline impairment and nutritional status. - Reason for missing information: Values related to baseline speed and deficiency in the original assessment question's identity are null. Data are unavailable to distinguish applicability according to the degree of baseline impairment and nutritional status. - Required materials and conditions: Data on baseline gait speed, nutrition and dietary assessment, deficiency testing, medications, and walking aids - Materials to obtain first: Data on baseline gait speed, nutrition and dietary assessment, deficiency testing, medications, and walking aids - Further research: Specify baseline functional and nutritional measures, and, if an effect-modification analysis is needed, prespecify its rationale and analysis plan. - Conditions for verification: Verify the actual baseline speed and nutrition-related selection criteria; do not substitute deficiency correction or healthy-participant results for this frailty question. - Why this condition is needed: Needed to avoid interpreting results from people with different baseline function or nutritional status as having the same scope of applicability. - Application exceptions: Do not newly impose a deficiency-treatment condition on a trial that did not select participants for deficiency. Retain deficiency status as unverified. - Remaining uncertainty: Values related to baseline speed and deficiency in the original assessment question's identity are null. Data are unavailable to distinguish applicability according to the degree of baseline impairment and nutritional status. - Referenced methods: M03 §3.2.1; detailed population conditions are internally designed / M03 §3.2.1–3.2.4; details concerning dose, persistence, and effect modification are internally designed - Related sources: S01, S02 ### N06 · Does 2,000 mg/day represent a value for which the actual intake and dosing schedule are also verified? Verification status: Partly verified Reading scope: The native summaries and values in the retained manuscript were read. External papers, official documents, and registrations remain unread in the current review. - Current findings: NADage's 2,000 mg/day is the planned daily NR amount. Amount per dose, daily frequency, dose escalation, basis for salt conversion, and actual intake are unverified. The conversion to 2 g/day in the original historical calculation is only a cross-check of mass units. - Why unverified: The planned daily amount is retained, but it is not actual exposure. The unit conversion also does not verify equivalence in salt or active-moiety amount. - Reason for missing information: The planned daily amount is retained, but it is not actual exposure. The unit conversion also does not verify equivalence in salt or active-moiety amount. - Required materials and conditions: Amount per dose, frequency, dose escalation, basis for salt conversion, and actual medication-taking and adherence records - Materials to obtain first: Amount per dose, frequency, dose escalation, basis for salt conversion, and actual medication-taking and adherence records - Further research: In the trial, collect records of each administration and adherence, discontinuations, and dose reductions, and distinguish the prespecified effect of assignment from analyses of actual exposure. - Conditions for verification: Distinguish the daily amount in the reported plan from actual exposure; do not invent an unknown amount per dose or adherence level. - Why this condition is needed: Needed because confusing the nominal dose with the exposure actually received changes how efficacy and safety apply. - Application exceptions: Do not calculate a new mass or salt conversion or an optimal dose. Distinguish information that may exist in the original paper from what remains unverified in the current input. - Remaining uncertainty: The planned daily amount is retained, but it is not actual exposure. The unit conversion also does not verify equivalence in salt or active-moiety amount. - Referenced methods: M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptation are internally designed / M03 §3.2.3, M08 §8.2.2–8.2.3; internal application - Related sources: S01 ### N07 · Is the 52-week plan linked to actual exposure, measurement, and follow-up after discontinuation? Verification status: Partly verified Reading scope: The native summaries and values in the retained manuscript were read. External papers, official documents, and registrations remain unread in the current review. - Current findings: The plan specifies 52 weeks of treatment and assessment at week 52. Actual exposure duration and separate follow-up after discontinuation are unverified. The original gait-speed result at that time point is also unverified. - Why unverified: The planned duration is known, but actual completion, exposure, and measurement times are unavailable. The plan cannot be read as evidence that long-term results or a maintenance effect exist. - Reason for missing information: The planned duration is known, but actual completion, exposure, and measurement times are unavailable. The plan cannot be read as evidence that long-term results or a maintenance effect exist. - Required materials and conditions: Records of actual initiation, discontinuation, the week 52 visit, observation windows, and follow-up after discontinuation - Materials to obtain first: Records of actual initiation, discontinuation, the week 52 visit, observation windows, and follow-up after discontinuation - Further research: Record visit windows, actual days of exposure, and missing data appropriate to the original question; if persistence is a separate objective, design follow-up after discontinuation separately. - Conditions for verification: Do not turn the planned 52 weeks of treatment and assessment into actual visits or a subsequent maintenance effect. - Why this condition is needed: Needed to distinguish the original question's change at 52 weeks from short-term effects or effects after discontinuation. - Application exceptions: Do not make all post-treatment follow-up studies mandatory for the current question. Separate the 52-week result from a distinct claim of persistence. - Remaining uncertainty: The planned duration is known, but actual completion, exposure, and measurement times are unavailable. The plan cannot be read as evidence that long-term results or a maintenance effect exist. - Referenced methods: M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptation are internally designed / M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptation is internally designed / M03 §3.2.1–3.2.4; details concerning dose, persistence, and effect modification are internally designed - Related sources: S01 ### N08 · Are the placebo composition, matching method, and common care in both groups verified? Verification status: Partly verified Reading scope: The native summaries and values in the retained manuscript were read. External papers, official documents, and registrations remain unread in the current review. - Current findings: The official registration index describes a placebo-comparison plan. The fields for the placebo's exact composition, matching method, and common care in both groups are null or unverified. - Why unverified: The comparator's name is verified, but it cannot be verified whether NR was the only actual difference or how blinding was implemented. - Reason for missing information: The comparator's name is verified, but it cannot be verified whether NR was the only actual difference or how blinding was implemented. - Required materials and conditions: Placebo composition, appearance/sensory matching, and rules for common medications, diet, exercise, and rehabilitation - Materials to obtain first: Placebo composition, appearance/sensory matching, and rules for common medications, diet, exercise, and rehabilitation - Further research: Disclose the placebo and common care, and record blinding for medication taking and assessment and differences in care between groups. - Conditions for verification: Distinguish the existence of a placebo plan from verification of the actual composition, blinding, and common care. - Why this condition is needed: The actual content of the control must be clear to distinguish NR's contribution to the comparison from influences on measurement. - Application exceptions: Do not conclude that an unverified composition means the placebo was absent or blinding failed. - Remaining uncertainty: The comparator's name is verified, but it cannot be verified whether NR was the only actual difference or how blinding was implemented. - Referenced methods: M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptation 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 - Related sources: S02 ### N09 · Are the actual implementation and concealment of the randomized, double-blind plan verified? Verification status: Partly verified Reading scope: The native summaries and values in the retained manuscript were read. External papers, official documents, and registrations remain unread in the current review. - Current findings: S01–S02 are retained as a randomized, double-blind, placebo-controlled plan. The full registration, actual allocation, concealment, baseline balance, and data on actual implementation and results have not been verified. - Why unverified: The design description in the public plan alone does not verify the actual allocation process. Do not reassess unknown implementation as either unbiased or failed. - Reason for missing information: The design description in the public plan alone does not verify the actual allocation process. Do not reassess unknown implementation as either unbiased or failed. - Required materials and conditions: Full protocol, allocation-sequence generation/concealment, and data on actual allocation and baseline balance - Materials to obtain first: Full protocol, allocation-sequence generation/concealment, and data on actual allocation and baseline balance - Further research: Document the actual allocation sequence, concealment, blinding, and baseline characteristics, and report results for the selected effect of assignment. - Conditions for verification: Distinguish the design label from actual allocation implementation; do not describe unverified implementation as actual nonimplementation. - Why this condition is needed: Needed because the label of a planned RCT alone does not establish that an actual causal comparison was implemented. - Application exceptions: Do not replace an unverified design status with nonapplicability of crossover or cluster designs. Retain the plan and actual implementation separately. - Remaining uncertainty: The design description in the public plan alone does not verify the actual allocation process. Do not reassess unknown implementation as either unbiased or failed. - Referenced methods: M08 §8.1–8.2.3; internal application - Related sources: S01, S02 ### N10 · Are the test distance, acceleration section, repetitions, and instrument for usual speed verified? Verification status: Unverified Reading scope: The native summaries and values in the retained manuscript were read. External papers, official documents, and registrations remain unread in the current review. - Current findings: The question concerns change in m/s at a usual, comfortable pace. The actual test distance, acceleration section, instrument, repetitions, walking aids, and assessor blinding are unverified. - Why unverified: target_endpoint defines the measurement concept for the question, but protocol_details is null. Matching units or the word gait alone does not establish that the tests are identical. - Reason for missing information: target_endpoint defines the measurement concept for the question, but protocol_details is null. Matching units or the word gait alone does not establish that the tests are identical. - Required materials and conditions: Usual-speed measurement manual, walking aids, assessors, repetitions, and unit definitions - Materials to obtain first: Usual-speed measurement manual, walking aids, assessors, repetitions, and unit definitions - Further research: Standardize the usual gait-speed procedure and specify assessment time points, aids, assessor blinding, and repeated measurements. - Conditions for verification: Verify the actual m/s test method for habitual/comfortable pace; do not substitute maximal speed or endurance speed. - Why this condition is needed: Needed to prevent differences in measurement methods from being mixed with actual functional change. - Application exceptions: Do not assume measurement is free of problems because the test is objective. Do not declare that information is unreported throughout the original source merely because it is absent from the plan. - Remaining uncertainty: target_endpoint defines the measurement concept for the question, but protocol_details is null. Matching units or the word gait alone does not establish that the tests are identical. - Referenced methods: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptation is internally designed / M08 Table 8.2.a, M03 §3.2.4; internal application - Related sources: S01, S02 ### N11 · Is NADage's 6-minute walk with concurrent sensors the same endpoint as usual speed over a short course? Verification status: Partly verified Reading scope: The native summaries and values in the retained manuscript were read. External papers, official documents, and registrations remain unread in the current review. - Current findings: The public plan for NADage, the closest study, describes a 6-minute walk with concurrent sensor gait assessment. Whether this is an endpoint equivalent to usual short-course gait speed has not been verified. - Why unverified: The endpoint's actual name in the plan is verified, but usual_gait_equivalence is not_verified. Creating usual gait speed from distance÷time does not resolve this gap. - Reason for missing information: The endpoint's actual name in the plan is verified, but usual_gait_equivalence is not_verified. Creating usual gait speed from distance÷time does not resolve this gap. - Required materials and conditions: Definitions of the 6-minute walk/sensors and data on equivalence with the usual-speed test and separately reported results - Materials to obtain first: Definitions of the 6-minute walk/sensors and data on equivalence with the usual-speed test and separately reported results - Further research: Measure the two tests separately, describe their protocols, units and observation windows, and report a usual gait speed estimate that matches the question. - Conditions for verification: Do not currently equate the planned 6-minute walk with usual gait speed; require actual verification of equivalence or a separate result. - Why this condition is needed: This is a key endpoint condition for upgrading the closest study to direct evidence of the effect. - Application exceptions: Do not deem it equivalent to comfortable walking over a short course merely because sensors collect speed. - Remaining uncertainty: The endpoint's actual name in the plan is verified, but usual_gait_equivalence is not_verified. Creating usual gait speed from distance÷time does not resolve this gap. - Referenced methods: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptation is internally designed / M08 Table 8.2.a, M03 §3.2.4; internal application - Related sources: S01, S02 ### N12 · Are the page's usual gait speed endpoint and its actual trial hierarchy as primary, secondary or post hoc verified? Verification status: Partly verified Reading scope: The native summaries and values in the retained manuscript were read. External papers, official documents, and registrations remain unread in the current review. - Current findings: Usual gait speed is this page's single editorial endpoint. The investigator page describes the 6-minute walk and sensor assessment as primary, but the field for the hierarchy of usual gait speed within the actual trial is null. - Why unverified: The two descriptions concern different things, so this alone is not designated a data conflict. The prespecified hierarchy and analysis plan for usual gait speed, and their agreement with the actual report, remain unverified. - Reason for missing information: The two descriptions concern different things, so this alone is not designated a data conflict. The prespecified hierarchy and analysis plan for usual gait speed, and their agreement with the actual report, remain unverified. - Required materials and conditions: The hierarchy of usual gait speed and reasons for changes in dated registration histories, protocols and analysis plans - Materials to obtain first: The hierarchy of usual gait speed and reasons for changes in dated registration histories, protocols and analysis plans - Further research: Specify the hierarchy and analysis of usual gait speed in the advance plan, and compare the reasons for changes in the actual report together with their dates. - Conditions for verification: Do not turn the page's single primary endpoint and the investigator page's description of the 6-minute walk as primary into a primary usual gait speed outcome within the trial. - Why this condition is needed: The editor's chosen question must be distinguished from the original trial's prespecified outcome selection. - Application exceptions: Do not treat failure to acquire the registration history as confirmation of nonregistration or selective reporting. - Remaining uncertainty: The two descriptions concern different things, so this alone is not designated a data conflict. The prespecified hierarchy and analysis plan for usual gait speed, and their agreement with the actual report, remain unverified. - Referenced methods: M08 Table 8.2.a, M04 §4.6.3; project-specific application / M03 §3.2.4, M15 §15.3.1–15.3.3; adaptation of outcomes to each question is project-specific - Related sources: S01, S02 ### N13 · Are the planned 100 participants distinguished from the actual enrolled, randomized, completed and usual gait speed analysis counts? Verification status: Partly verified Reading scope: The native summaries and values in the retained manuscript were read. External papers, official documents, and registrations remain unread in the current review. - Current findings: NADage's 100 participants are a planned count. Actual enrollment, randomization, completion and usual gait speed analysis counts remain unverified. - Why unverified: The nature of the planned n is clear, but actual sample-flow data are unavailable. The 100 participants cannot be converted into a per-group n or an analysis denominator. - Reason for missing information: The nature of the planned n is clear, but actual sample-flow data are unavailable. The 100 participants cannot be converted into a per-group n or an analysis denominator. - Required materials and conditions: Participant flow diagram; enrollment, allocation and completion by group; usual gait speed analysis denominators and reasons for exclusion - Materials to obtain first: Participant flow diagram; enrollment, allocation and completion by group; usual gait speed analysis denominators and reasons for exclusion - Further research: Report the actual sample flow at each stage, the corresponding usual gait speed analysis n and reasons for missingness alongside the results. - Conditions for verification: Do not use planned enrollment as the outcome analysis n; link the actual denominators at each stage. - Why this condition is needed: This is needed to avoid claiming precision of an effect or completion on the basis of a planned number. - Application exceptions: Do not create a recruitment status or analysis count at the cutoff solely from historical wording that enrollment had actually begun. - Remaining uncertainty: The nature of the planned n is clear, but actual sample-flow data are unavailable. The 100 participants cannot be converted into a per-group n or an analysis denominator. - Referenced methods: M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; adaptation by study design is project-specific - Related sources: S01, S02 ### N14 · Can the latest recruitment and results-posting status as of the reference date be verified? Verification status: Unverified Reading scope: The native summaries and values in the retained manuscript were read. External papers, official documents, and registrations remain unread in the current review. - Current findings: The wording on the investigator page about recruitment starting is a historical record. S02's directly accessed body was a glossary-only application shell, and the latest status, registration history and posted results were not verified at that time. - Why unverified: The registry was not accessed in the current work. Do not read the generic word Withdrawn in the shell seen at that time as this trial's withdrawal status, or conclude that no latest results exist. - Reason for missing information: The registry was not accessed in the current work. Do not read the generic word Withdrawn in the shell seen at that time as this trial's withdrawal status, or conclude that no latest results exist. - Required materials and conditions: NCT06208527 registration history, status and posted results documents as of the relevant reference date - Materials to obtain first: NCT06208527 registration history, status and posted results documents as of the relevant reference date - Further research: Verification of suitable materials means linking registry versions and results documents to their dates at the time; it is distinct from conducting a new trial itself. - Conditions for verification: Distinguish the historical description of recruitment starting and the registry index from the actual status/posted results as of the reference date. - Why this condition is needed: This is needed to avoid wrongly attributing generic wording on the registry screen to the trial's actual progress. - Application exceptions: Distinguish the current status of access not attempted from the failure to acquire the body text at that earlier time. Do not use a valid response with 0 results or an unverified status to mean that research does not exist. - Remaining uncertainty: The registry was not accessed in the current work. Do not read the generic word Withdrawn in the shell seen at that time as this trial's withdrawal status, or conclude that no latest results exist. - Referenced methods: M04 §4.5–4.6 principles for data collection/selection; separation of access from reading and the hyperlink contract are project-specific / M04 §4.5, §4.6.3; limits on conversion of current materials follow the user's scope and project-specific design / M08 Table 8.2.a, M04 §4.6.3; project-specific application - Related sources: S01, S02 ### N15 · Are the actual between-group analysis, ITT/PP and adjustment for usual gait speed verified? Verification status: Unverified Reading scope: The native summaries and values in the retained manuscript were read. External papers, official documents, and registrations remain unread in the current review. - Current findings: The question concerns the between-group difference in change in usual gait speed from baseline to 52 weeks under treatment assignment. The actual analysis population, ITT/PP, adjusted model and results remain unverified. - Why unverified: The estimand in the original question identity is the requested question. It cannot automatically be elevated to an analysis performed in the actual trial. - Reason for missing information: The estimand in the original question identity is the requested question. It cannot automatically be elevated to an analysis performed in the actual trial. - Required materials and conditions: Documents defining the estimand of interest, analysis population, model, adjustment and actual results - Materials to obtain first: Documents defining the estimand of interest, analysis population, model, adjustment and actual results - Further research: Prespecify the effect of interest, handling of missingness and adherence, and adjustment in the analysis plan, and report an estimate for that contrast. - Conditions for verification: Distinguish the question of the NR−placebo effect of assignment on change from baseline to 52 weeks from the actual analysis. - Why this condition is needed: This is needed to avoid treating within-group change, the effect of adherence and the planned effect of assignment as the same actual between-group value. - Application exceptions: Do not fill unverified analysis information with an arbitrary ITT, complete-case or PP analysis. - Remaining uncertainty: The estimand in the original question identity is the requested question. It cannot automatically be elevated to an analysis performed in the actual trial. - Referenced methods: M08 §8.2.2, M15 §15.3.1; project-specific application - Related sources: S01, S02 ### N16 · Who was missing from the 52-week speed measurement, and how was this handled? Verification status: Unverified Reading scope: The native summaries and values in the retained manuscript were read. External papers, official documents, and registrations remain unread in the current review. - Current findings: Actual completion and usual gait speed analysis counts and the reasons for missing measurements are not verified in the retained materials. Observation losses cannot be assessed solely from the planned 52 weeks and 100 participants. - Why unverified: Without actual sample flow and analysis data, the adequacy of missing-data handling or completeness of follow-up cannot be judged. - Reason for missing information: Without actual sample flow and analysis data, the adequacy of missing-data handling or completeness of follow-up cannot be judged. - Required materials and conditions: Missed visits, discontinuation, death/illness, inability to measure, handling of missingness and sensitivity analyses by group - Materials to obtain first: Missed visits, discontinuation, death/illness, inability to measure, handling of missingness and sensitivity analyses by group - Further research: Report visit flow, including discontinuation, death and inability to measure, together with prespecified handling of missingness and sensitivity analyses. - Conditions for verification: Link actual measurement and analysis denominators to reasons for missingness; do not turn unverified information into no attrition or 0 events. - Why this condition is needed: This is needed to distinguish values from only those with measured outcomes from the effect of assignment during long-term observation of frail participants. - Application exceptions: Do not turn the possibility of missingness into a confirmed magnitude of actual bias or a finding that the trial is invalid. - Remaining uncertainty: Without actual sample flow and analysis data, the adequacy of missing-data handling or completeness of follow-up cannot be judged. - Referenced methods: M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; adaptation by study design is project-specific / M08 §8.2.2, M15 §15.3.1; project-specific application - Related sources: S01, S02 ### N17 · Are direct usual gait speed changes, the between-group difference and CI verified? Verification status: Unverified Reading scope: The native summaries and values in the retained manuscript were read. External papers, official documents, and registrations remain unread in the current review. - Current findings: The original values, changes, between-group estimate and CI for directly eligible usual gait speed remain unverified. target_between_group_effect_mps and target_ci are null. - Why unverified: The currently retained materials include plans and results for other questions. Failure to verify direct results does not mean that the effect is 0 or that all human research is absent. - Reason for missing information: The currently retained materials include plans and results for other questions. Failure to verify direct results does not mean that the effect is 0 or that all human research is absent. - Required materials and conditions: Group-specific original usual gait speed values/changes, between-group estimate and CI for the fixed population, exposure and time point - Materials to obtain first: Group-specific original usual gait speed values/changes, between-group estimate and CI for the fixed population, exposure and time point - Further research: An eligible study reports group-specific results for the defined usual gait speed test together with the estimate, CI and denominator for the selected contrast. - Conditions for verification: Link the m/s result corresponding to the original question; if absent, leave the value null. - Why this condition is needed: This is a key condition for distinguishing the existence of direct results from plans and adjacent numerical findings. - Application exceptions: Do not convert distance, within-group P values or NAD values into a direct between-group effect in m/s. - Remaining uncertainty: The currently retained materials include plans and results for other questions. Failure to verify direct results does not mean that the effect is 0 or that all human research is absent. - Referenced methods: M03 §3.2.4, M15 §15.3.1–15.3.3; adaptation of outcomes to each question is project-specific / M15 §15.3.1–15.3.3; project-specific application - Related sources: S01, S02 ### N18 · Are the SD, SE, covariance and interval type for the target change verified? Verification status: Unverified Reading scope: The native summaries and values in the retained manuscript were read. External papers, official documents, and registrations remain unread in the current review. - Current findings: The analysis denominator and CI for the target result remain unverified. The manuscript states that it did not estimate or fill in the target CI, SD, SE or covariance. - Why unverified: No observed variance is available for calculating a new standardized effect or precision. The one-sided 90% interval from PAD pertains to a different endpoint. - Reason for missing information: No observed variance is available for calculating a new standardized effect or precision. The one-sided 90% interval from PAD pertains to a different endpoint. - Required materials and conditions: Variance type, analysis n and model for usual gait speed change, and the reported between-group interval - Materials to obtain first: Variance type, analysis n and model for usual gait speed change, and the reported between-group interval - Further research: Disclose the variance type, denominator, interval construction and analysis model for the relevant usual gait speed result. - Conditions for verification: Use only variance and intervals belonging to the direct result; do not import SD or a one-sided CI from another trial. - Why this condition is needed: This is needed to avoid creating a nonexistent interval by combining numerical values with different variance types or targets. - Application exceptions: Do not use an assumed variance in a plan as an actually observed variance. Do not make a broad declaration of nonreporting by saying it is absent from the original text either. - Remaining uncertainty: No observed variance is available for calculating a new standardized effect or precision. The one-sided 90% interval from PAD pertains to a different endpoint. - Referenced methods: M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; adaptation by study design is project-specific / M15 §15.3.1–15.3.3; project-specific application - Related sources: S01, S02 ### N19 · Is a clinically important between-group difference appropriate to this frail population and test verified? Verification status: Unverified Reading scope: The native summaries and values in the retained manuscript were read. External papers, official documents, and registrations remain unread in the current review. - Current findings: The applicable between-group MCID field is null. The original question separately requires a valid between-group estimate and an interpretation of clinical importance appropriate to the population and test. - Why unverified: The clinical importance for this question cannot be determined from another gait test, a threshold for individual change or a planned participant count. Exclusion of an important benefit has not been verified either. - Reason for missing information: The clinical importance for this question cannot be determined from another gait test, a threshold for individual change or a planned participant count. Exclusion of an important benefit has not been verified either. - Required materials and conditions: Evidence for a clinically important between-group difference for the relevant frail population and usual gait speed protocol - Materials to obtain first: Evidence for a clinically important between-group difference for the relevant frail population and usual gait speed protocol - Further research: First justify the evidence for an important difference appropriate to the population, test and between-group contrast, then interpret it alongside the estimated interval. - Conditions for verification: Distinguish statistical success from clinical importance, and do not set an unsupported common MCID, minimum participant count or duration. - Why this condition is needed: This is needed to avoid equating nominal statistical significance with a clinically important improvement in usual gait speed. - Application exceptions: Because the usual gait speed value itself is the original question, do not impose a separate mortality trial as a prerequisite for that value. - Remaining uncertainty: The clinical importance for this question cannot be determined from another gait test, a threshold for individual change or a planned participant count. Exclusion of an important benefit has not been verified either. - Referenced methods: M15 §15.3.1–15.3.3; project-specific application - Related sources: S01, S02 ### N20 · Are the plan's funding, product provision and authors' conflicts of interest directly verified? Verification status: Partly verified Reading scope: The native summaries and values in the retained manuscript were read. External papers, official documents, and registrations remain unread in the current review. - Current findings: The record that S01 contains funding information and the relevant location are retained. Because no directly eligible result has been verified, the original independence axis is null. This retained summary contains no extracted values for the specific funding source, product provision or all author roles, so their content was not inferred. - Why unverified: The existence and location of funding information are recorded, but the level of actual content in the current input is limited. Do not copy ChromaDex relationships from other NR trials as NADage's provision information. - Reason for missing information: The existence and location of funding information are recorded, but the level of actual content in the current input is limited. Do not copy ChromaDex relationships from other NR trials as NADage's provision information. - Required materials and conditions: NADage's original funding information, product provision, author roles, and patent/employment/declared conflicts of interest - Materials to obtain first: NADage's original funding information, product provision, author roles, and patent/employment/declared conflicts of interest - Further research: Link funding, product provision and author roles to the results data, and verify the actual study families when claiming independent replication. - Conditions for verification: Separate the existence of a funding description from full verification of provision/conflicts of interest, and do not assign an independence score to a missing result. - Why this condition is needed: This is needed to avoid inferring independent funding or manufacturer involvement from an unverified supply chain. - Application exceptions: Do not exclude a result solely because a conflict of interest exists. Do not use unverified information as evidence of independence. - Remaining uncertainty: The existence and location of funding information are recorded, but the level of actual content in the current input is limited. Do not copy ChromaDex relationships from other NR trials as NADage's provision information. - Referenced methods: Chamgap's own conditions for independence and attribution. The official methods sections used in this pilot do not endorse all of these detailed items - Related sources: S01 ### N21 · Are plans, papers, registrations and corrections kept from being double-counted as independent trials of effect? Verification status: Partly verified Reading scope: The native summaries and values in the retained manuscript were read. External papers, official documents, and registrations remain unread in the current review. - Current findings: The native evidence distinguishes NADage F01, NR-VETS F02, Orr MCI F03, the healthy-adult crossover F04 and NICE PAD F05. S01–S02, S03–S04 and S09–S10 are related reports within their respective families; retain the narrow original record that the number of directly eligible results is 0. - Why unverified: The 5 family descriptions and 15 actual citations record existence; they are not counts of direct usual gait speed trials or unique participants. Within the S05–S07 range notation in evidence, individual S06/S07 citations are absent from the current list and must not be created. - Reason for missing information: The 5 family descriptions and 15 actual citations record existence; they are not counts of direct usual gait speed trials or unique participants. Within the S05–S07 range notation in evidence, individual S06/S07 citations are absent from the current list and must not be created. - Required materials and conditions: A mapping of report identifiers, native F01–F05 relationships, and eligible results/endpoints/time points - Materials to obtain first: A mapping of report identifiers, native F01–F05 relationships, and eligible results/endpoints/time points - Further research: When collecting materials, verify the relationships between registration numbers/DOIs and results/time points/analyses to link multiple reports of the same study. - Conditions for verification: Group the investigator page and registration for the same plan, and papers/corrections for the same trial, leaving unresolved unique trial and participant counts null. - Why this condition is needed: This is needed to avoid erasing gaps by counting materials as human trials or replication confirmations. - Application exceptions: If bibliographic details or report families are unresolved, retain provisional relationships and omissions; do not create new reports. - Remaining uncertainty: The 5 family descriptions and 15 actual citations record existence; they are not counts of direct usual gait speed trials or unique participants. Within the S05–S07 range notation in evidence, individual S06/S07 citations are absent from the current list and must not be created. - Referenced methods: M04 §4.6.1–4.6.2 distinction between studies and reports; cohort/outcome linkage is a project-specific application / M04 §4.6.1–4.6.2, M15 §15.3.1; project-specific application - Related sources: S01, S02, S03, S04, S05, S08, S09, S10 ### N22 · Is the NR-VETS population the same as the selected frail population with Fried scores of 3 or higher? Verification status: Not met Reading scope: The native summaries and values in the retained manuscript were read. External papers, official documents, and registrations remain unread in the current review. - Current findings: The institutional index for NR-VETS describes non-frail and prefrail participants, Fried<3. This does not match the Fried≥3 population criterion for this question, and the complete protocol and target results remain unverified. - Why unverified: The population described in the currently retained index differs from the fixed question. This does not mean that NR-VETS has no efficacy or that exclusion of frail participants across all amended versions has been established. - Reason for missing information: The population described in the currently retained index differs from the fixed question. This does not mean that NR-VETS has no efficacy or that exclusion of frail participants across all amended versions has been established. - Required materials and conditions: Complete NR-VETS eligibility criteria, amendment history and usual gait speed results by frailty stratum - Materials to obtain first: Complete NR-VETS eligibility criteria, amendment history and usual gait speed results by frailty stratum - Further research: Verify separate results by frailty stratum in that study, or perform the same usual gait speed comparison in the selected Fried≥3 population. - Conditions for verification: Distinguish the Fried<3 description in the currently retained official institutional index from the selected frailty criterion, leaving the latest amendments or target-stratum results unverified. - Why this condition is needed: This is needed to avoid repurposing prefrail or non-frail results as direct results for the target frail population. - Application exceptions: Reconsider eligibility if the latest complete registration is acquired and shows population amendments or separate results. - Remaining uncertainty: The population described in the currently retained index differs from the fixed question. This does not mean that NR-VETS has no efficacy or that exclusion of frail participants across all amended versions has been established. - Referenced methods: M03 §3.2.1; detailed population conditions are project-specific / M04 §4.6.1–4.6.2, M15 §15.3.1; project-specific application - Related sources: S03, S04 ### N23 · Are Orr's two p-values a between-group effect on usual gait speed in frail participants? Verification status: Not met Reading scope: The native summaries and values in the retained manuscript were read. External papers, official documents, and registrations remain unread in the current review. - Current findings: In Orr MCI, placebo p=0.0402 and NR p=0.4698 are tests of within-group walking-speed change in each group. They are not a between-group effect in m/s, and the clinical MCI eligibility criteria differ from the frailty eligibility conditions for this question. - Why unverified: A difference in significance between the two within-group tests is not a test of the between-group effect. The target population, protocol and between-group estimate have not been verified, so these cannot be used as direct results. - Reason for missing information: A difference in significance between the two within-group tests is not a test of the between-group effect. The target population, protocol and between-group estimate have not been verified, so these cannot be used as direct results. - Required materials and conditions: Orr's gait test, actual between-group m/s estimate/CI and results tables by population - Materials to obtain first: Orr's gait test, actual between-group m/s estimate/CI and results tables by population - Further research: Report a direct between-group estimate appropriate to the population of interest and usual gait speed test, and distinguish it from within-group results. - Conditions for verification: Do not read the respective within-group p-values for placebo and NR as a between-group test or a result for the target frail population. - Why this condition is needed: Within-group contrasts must be distinguished from an actual between-group difference. - Application exceptions: Retain within-group p-values as original adjacent results, but do not calculate a new difference or CI. - Remaining uncertainty: A difference in significance between the two within-group tests is not a test of the between-group effect. The target population, protocol and between-group estimate have not been verified, so these cannot be used as direct results. - Referenced methods: M03 §3.2.4, M15 §15.3.1–15.3.3; adaptation of outcomes to each question is project-specific / M08 §8.2.2, M15 §15.3.1; project-specific application / M04 §4.6.1–4.6.2, M15 §15.3.1; project-specific application - Related sources: S05 ### N24 · Are Orr's actual completion count, gait analysis denominator and dosing schedule verified? Verification status: Partly verified Reading scope: The native summaries and values in the retained manuscript were read. External papers, official documents, and registrations remain unread in the current review. - Current findings: Orr’s abstract and figure captions record 20 completers. The total number randomized and the gait-outcome analysis denominator are unverified in this manuscript. The historical calculation cross-checking the phases 1+1+1+6 against 9 weeks records ambiguity in the abstract’s duration wording; it does not constitute a correction of the original table or a target 52-week result. - Why unverified: Only the completed count and a cross-check of the historical schedule are available; an analysis count for the target population is absent. That calculation is not presented as a new clinical calculation or as confirmed actual treatment days. - Reason for missing information: Only the completed count and a cross-check of the historical schedule are available; an analysis count for the target population is absent. That calculation is not presented as a new clinical calculation or as confirmed actual treatment days. - Required materials and conditions: Orr’s participant flow by stage, gait-analysis n, dose escalation/treatment days, and data for the target frail population - Materials to obtain first: Orr’s participant flow by stage, gait-analysis n, dose escalation/treatment days, and data for the target frail population - Further research: For adjacent evidence, verify the actual participant flow and analysis denominator in its original table; assess the target comparison using a separate eligible population and 52-week results. - Conditions for verification: Do not repurpose the 20 completers or descriptions of schedules from other trials as the analysis denominator or 52-week duration for the target usual gait speed. - Why this condition is needed: Needed to prevent the completed counts and schedules of adjacent trials from being imported as the exposure and denominator for the direct question. - Application exceptions: Detailed counts that may appear in another retained assessment of the same Orr family are not automatically imported into this manuscript. - Remaining uncertainty: Only the completed count and a cross-check of the historical schedule are available; an analysis count for the target population is absent. That calculation is not presented as a new clinical calculation or as confirmed actual treatment days. - Referenced methods: M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; adaptations by study design are internally designed / M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptations are internally designed / M03 §3.2.1–3.2.4; details on dose, persistence, and effect modification are internally designed - Related sources: S05 ### N25 · Are Martens’ motor-function results in healthy participants equivalent to the target frailty comparison? Verification status: Not met Reading scope: The native summaries and values in the retained manuscript were read. External papers, official documents, and registrations remain unread in the current review. - Current findings: Martens’ crossover trial in healthy middle-aged and older adults reported no improvement in overall motor function. Baseline function and the regimen differ, and no target usual-speed values were reconstructed from the supplementary motor-function figures. - Why unverified: The population and regimen differ from the fixed question of frailty, 2,000 mg/day, and 52 weeks. The adjacent trial’s no-difference result is retained, but it is not used as evidence that the target effect is 0. - Reason for missing information: The population and regimen differ from the fixed question of frailty, 2,000 mg/day, and 52 weeks. The adjacent trial’s no-difference result is retained, but it is not used as evidence that the target effect is 0. - Required materials and conditions: Exposure, duration, baseline function, usual-speed results, and crossover analysis in the healthy-participant crossover trial - Materials to obtain first: Exposure, duration, baseline function, usual-speed results, and crossover analysis in the healthy-participant crossover trial - Further research: Verify results using the same frail population, exposure, and test; when using crossover data, report period, sequence, and carryover effects and a paired analysis. - Conditions for verification: Do not aggregate statements of no difference in motor function among healthy participants as repeated refutations of the target frailty comparison. - Why this condition is needed: Needed to retain the existence of contrary results while preventing refutation in a different population from being transferred to this question. - Application exceptions: Retain the original crossover design, but do not estimate the paired variance for the target usual speed from these data. - Remaining uncertainty: The population and regimen differ from the fixed question of frailty, 2,000 mg/day, and 52 weeks. The adjacent trial’s no-difference result is retained, but it is not used as evidence that the target effect is 0. - Referenced methods: M03 §3.2.1; detailed population criteria are internally designed / M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses is internally designed / M08 §8.2.2, M15 §15.3.1; internal application / M04 §4.6.1–4.6.2, M15 §15.3.1; internal application - Related sources: S08 ### N26 · Is NICE’s +17.6 m an effect on usual gait speed in m/s in the frail population? Verification status: Not met Reading scope: The native summaries and values in the retained manuscript were read. External papers, official documents, and registrations remain unread in the current review. - Current findings: NICE PAD randomized 90 participants overall. The 6-month between-group result for 6-minute walk distance, +17.6 m, is a positive adjacent result. WIQ speed is a self-reported score; these values are not usual-gait-speed results in m/s for the target frail population. - Why unverified: The positive signal is retained, but the population, endpoint, and time point differ from the fixed question. Do not use the 90 randomized overall as the analysis n for the target speed or calculate distance÷time. - Reason for missing information: The positive signal is retained, but the population, endpoint, and time point differ from the fixed question. Do not use the 90 randomized overall as the analysis n for the target speed or calculate distance÷time. - Required materials and conditions: NICE’s original 6-minute-walk table and separate usual-speed results for the selected frail population - Materials to obtain first: NICE’s original 6-minute-walk table and separate usual-speed results for the selected frail population - Further research: Measure usual speed separately in the target frail population and report the selected contrast, time point, and denominator. - Conditions for verification: Retain the positive 6-month result for 6-minute walk distance in its original unit, population, and contrast; do not divide by time to create a usual-speed result. - Why this condition is needed: Needed to retain positive adjacent results without elevating them to direct efficacy evidence. - Application exceptions: Attribute the original +17.6 m and the historical 7.0−(−10.6) cross-check only to that PAD distance result. - Remaining uncertainty: The positive signal is retained, but the population, endpoint, and time point differ from the fixed question. Do not use the 90 randomized overall as the analysis n for the target speed or calculate distance÷time. - Referenced methods: M03 §3.2.4, M15 §15.3.1–15.3.3; adaptations of outcomes to each question are internally designed / M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; adaptations by study design are internally designed / M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses is internally designed / M04 §4.6.1–4.6.2, M15 §15.3.1; internal application - Related sources: S09 ### N27 · Are NICE’s one-sided 90% CI and p=0.08 distinguished from its study-specific criterion? Verification status: Verified Reading scope: The native summaries and values in the retained manuscript were read. External papers, official documents, and registrations remain unread in the current review. - Current findings: NICE’s adjacent distance result is a one-sided 90% CI [+1.77,+∞) m and p=0.08. The manuscript explains that it met the study’s prespecified significance criterion. It was not reclassified as a failure under a universal p<.05 criterion. - Why unverified: The manuscript retains the interval type, lower bound, open upper bound, and explanation of the study-specific criterion. This does not mean that statistical or clinical success for the target usual speed has been verified. - Reason for missing information: The manuscript retains the interval type, lower bound, open upper bound, and explanation of the study-specific criterion. This does not mean that statistical or clinical success for the target usual speed has been verified. - Required materials and conditions: NICE’s prespecified statistical criterion, definition of the one-sided interval, and location of the original between-group report - Materials to obtain first: NICE’s prespecified statistical criterion, definition of the one-sided interval, and location of the original between-group report - Further research: Future direct studies should disclose the prespecified statistical criterion, interval type, and contrast of interest alongside the results, distinguishing these from clinical importance. - Conditions for verification: Do not convert the reported one-sided 90% interval’s lower bound and open upper bound +∞, or p=0.08, into a two-sided 95% interval or a CI in the target m/s unit. - Why this condition is needed: Needed to avoid changing the meaning by misrepresenting the adjacent study’s interval type and study-specific criterion. - Application exceptions: Do not calculate a new two-sided CI, standardized effect, or MCID. Verify only at the level of the explanation in the manuscript at that time. - Remaining uncertainty: The manuscript retains the interval type, lower bound, open upper bound, and explanation of the study-specific criterion. This does not mean that statistical or clinical success for the target usual speed has been verified. - Referenced methods: M03 §3.2.4, M15 §15.3.1–15.3.3; adaptations of outcomes to each question are internally designed / M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses is internally designed / M15 §15.3.1–15.3.3; internal application / M08 Table 8.2.a, M04 §4.6.3; internal application - Related sources: S09 ### N28 · Are the actual content of the NICE correction notice and its impact on the results verified? Verification status: Partly verified Reading scope: The native summaries and values in the retained manuscript were read. External papers, official documents, and registrations remain unread in the current review. - Current findings: The record states that the existence and identifier of the 2024-08-12 NICE publisher correction were verified in the original article’s change history. The content of the correction notice was not acquired at that time. - Why unverified: The existence of the correction notice is retained, but its body, what was changed, and its impact on the results are unverified. Do not automatically describe it as a retraction or a correction to an effect estimate. - Reason for missing information: The existence of the correction notice is retained, but its body, what was changed, and its impact on the results are unverified. Do not automatically describe it as a retraction or a correction to an effect estimate. - Required materials and conditions: The original article’s change history, the full correction notice, and links between results/tables before and after the correction - Materials to obtain first: The original article’s change history, the full correction notice, and links between results/tables before and after the correction - Further research: When reviewing materials, compare what the full correction notice changes with the original table and record it. This is a verification task distinct from designing a new clinical trial. - Conditions for verification: Distinguish the correction notice’s existence/DOI from its content, and do not speculate about what was corrected. - Why this condition is needed: Needed to prevent bibliographic information about a correction from being overstated as a review of its content or verification of changes to results. - Application exceptions: Do not label the lack of an attempt this time as an actual access failure at that earlier time. - Remaining uncertainty: The existence of the correction notice is retained, but its body, what was changed, and its impact on the results are unverified. Do not automatically describe it as a retraction or a correction to an effect estimate. - Referenced methods: M04 §4.5–4.6 principles for data collection/selection; separation of access from reading and the hyperlink contract are internally designed / M04 §4.5, §4.6.3; limits on conversion to current materials derive from the user-defined scope and internal design / M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses is internally designed - Related sources: S09, S10 ### N29 · Are NMN, NAM, niacin, and tryptophan materials evidence for NR alone? Verification status: Not met Reading scope: The native summaries and values in the retained manuscript were read. External papers, official documents, and registrations remain unread in the current review. - Current findings: S13 concerns tryptophan, nicotinic acid, and nicotinamide; S14 concerns NMN. The S17 NICE-FIT title contains nicotinamide. Candidates not verified as NR are not used as direct NR evidence. - Why unverified: The retained substance identity differs from the requested NR or is not verified as NR. Positive gait results for NMN also do not verify a direct NR effect because the molecule differs. - Reason for missing information: The retained substance identity differs from the requested NR or is not verified as NR. Positive gait results for NMN also do not verify a direct NR effect because the molecule differs. - Required materials and conditions: The actual active ingredient, product composition, endpoint, and population identity of candidate studies - Materials to obtain first: The actual active ingredient, product composition, endpoint, and population identity of candidate studies - Further research: When checking study eligibility, verify the active molecule, salt, and composition, and design a separate direct study for the NR question. - Conditions for verification: Do not use other molecules as synonyms for NR, and do not change nicotinamide in the NICE-FIT title to NR. - Why this condition is needed: Needed to prevent distinct exposures from being merged under the collective term NAD precursors. - Application exceptions: Do not elevate a record of screening the substance from the title to verification of the full product composition or reading of the full results text. - Remaining uncertainty: The retained substance identity differs from the requested NR or is not verified as NR. Positive gait results for NMN also do not verify a direct NR effect because the molecule differs. - Referenced methods: M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptations are internally designed / M04 §4.6.1–4.6.2, M15 §15.3.1; internal application - Related sources: S13, S14, S17 ### N30 · Is the NR+exercise trial in hypertension a contrast of NR alone for gait speed in frailty? Verification status: Not met Reading scope: The native summaries and values in the retained manuscript were read. External papers, official documents, and registrations remain unread in the current review. - Current findings: S15 is a pilot trial of NR+exercise in middle-aged and older adults with hypertension. The record is of screening at the level of the publisher’s abstract and bibliographic back matter; it was not counted as a direct replication of usual-speed results in the target frail population. - Why unverified: The population and concurrent intervention in the screening record differ from the fixed question. Separation of exercise by arm and the target speed results were not verified. - Reason for missing information: The population and concurrent intervention in the screening record differ from the fixed question. Separation of exercise by arm and the target speed results were not verified. - Required materials and conditions: S15’s exercise requirements in both arms, NR contrast, frail stratum, and usual-speed results - Materials to obtain first: S15’s exercise requirements in both arms, NR contrast, frail stratum, and usual-speed results - Further research: Specify the exercise common to both arms and the NR difference, or separate their contributions using a factorial design, and measure usual speed in the target frail stratum. - Conditions for verification: Distinguish the combination with aerobic exercise in participants with hypertension from the target contrast of NR alone versus placebo. - Why this condition is needed: Needed to avoid confusing the contribution of exercise with that of NR alone. - Application exceptions: Do not state that review of the full results and exercise control is complete on the basis of screening only the publisher’s abstract. - Remaining uncertainty: The population and concurrent intervention in the screening record differ from the fixed question. Separation of exercise by arm and the target speed results were not verified. - 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 / M04 §4.6.1–4.6.2, M15 §15.3.1; internal application - Related sources: S15 ### N31 · Does the combination-product cognition study in senior dogs address the NR gait question in older humans? Verification status: Not met Reading scope: The native summaries and values in the retained manuscript were read. External papers, official documents, and registrations remain unread in the current review. - Current findings: S18 concerns a senolytic/NAD-precursor combination and owner-assessed cognition in senior dogs. It was excluded at screening because the species, intervention, and endpoint differ, and no dog effect estimates were used. - Why unverified: The actual question in the archived bibliographic record differs from the selected question about gait with NR alone in humans. The title/abstract screening record is not a refutation of human research. - Reason for missing information: The actual question in the archived bibliographic record differs from the selected question about gait with NR alone in humans. The title/abstract screening record is not a refutation of human research. - Required materials and conditions: S18’s species, active ingredients, and measured outcomes, and direct evidence in humans - Materials to obtain first: S18’s species, active ingredients, and measured outcomes, and direct evidence in humans - Further research: A direct comparison with the target human population, exposure to the single intervention, and a usual-speed test is needed. - Conditions for verification: Do not transfer combination-product and owner-assessed cognition results in dogs to usual speed with NR alone in humans. - Why this condition is needed: Needed to prevent automatic attribution of nonhuman, combination-product, and other-function data to this question. - Application exceptions: Retain nonhuman materials as identity-screening records, but do not add them to the count of human trials. - Remaining uncertainty: The actual question in the archived bibliographic record differs from the selected question about gait with NR alone in humans. The title/abstract screening record is not a refutation of human research. - Referenced methods: M03 §3.2.1; detailed population criteria are internally designed / M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptations are internally designed / M03 §3.2.4, M15 §15.3.1–15.3.3; adaptations of outcomes to each question are internally designed - Related sources: S18 ### N32 · Are direct usual-speed results verified separately from NAD increases, SPPB, strength, and fatigue? Verification status: Unverified Reading scope: The native summaries and values in the retained manuscript were read. External papers, official documents, and registrations remain unread in the current review. - Current findings: NAD increases, SPPB, chair rises, strength, fatigue, and usual gait speed are different outcomes. P on the original axis denotes a functional endpoint performed by the patient; it does not mean that a direct effect has been verified. - Why unverified: Signals from other measures or the existence of a functional-test battery cannot fill in the between-group difference for the target usual speed. That direct value is currently null. - Reason for missing information: Signals from other measures or the existence of a functional-test battery cannot fill in the between-group difference for the target usual speed. That direct value is currently null. - Required materials and conditions: A report distinguishing direct results for the target usual speed from other functional and biochemical results - Materials to obtain first: A report distinguishing direct results for the target usual speed from other functional and biochemical results - Further research: Measure the selected usual speed separately from mechanisms and other functions, and prespecify and report each contrast of interest. - Conditions for verification: Do not substitute mechanism or other tests for the selected functional endpoint, or vice versa; require direct results for this question. - Why this condition is needed: Needed to prevent mechanism and function from automatically being interpreted as the same outcome. - Application exceptions: Because the functional score itself is the original question, do not require separate death events as a prerequisite for that value. - Remaining uncertainty: Signals from other measures or the existence of a functional-test battery cannot fill in the between-group difference for the target usual speed. That direct value is currently null. - Referenced methods: M03 §3.2.4, M15 §15.3.1–15.3.3; adaptations of outcomes to each question are internally designed / M03 §3.2.4; internally defined scope-expansion boundary - Related sources: S05, S08, S09 ### N33 · Are events, discontinuations, and denominators verified for this plan in the frail population at 2,000 mg/day for 52 weeks? Verification status: Unverified Reading scope: The native summaries and values in the retained manuscript were read. External papers, official documents, and registrations remain unread in the current review. - Current findings: Adverse events, discontinuations, and long-term safety are unverified for the high-dose, long-term plan in the target frail population. Caution in the original safety label does not mean that NR harm has been established. - Why unverified: Event frequency or causality cannot be assessed because records are absent for event definitions, systematic/spontaneous collection, exposure denominators, temporal order, discontinuation/recovery, between-arm comparisons, other causes, and missing data. - Reason for missing information: Event frequency or causality cannot be assessed because records are absent for event definitions, systematic/spontaneous collection, exposure denominators, temporal order, discontinuation/recovery, between-arm comparisons, other causes, and missing data. - Required materials and conditions: Arm-specific AE/SAE, numbers of people and events, discontinuations, collection periods, and collection methods for the same population, product, and exposure - Materials to obtain first: Arm-specific AE/SAE, numbers of people and events, discontinuations, collection periods, and collection methods for the same population, product, and exposure - Further research: In long-term comparisons, collect event definitions, collection schedules, discontinuations, exposure time, concomitant treatments, and arm-specific numbers of people and events. Consider follow-up designs suited to rare events separately. - Conditions for verification: Distinguish an efficacy plan from direct safety data, and do not record unverified events as 0 or as confirmation of safety. - Why this condition is needed: Needed to prevent data gaps from being elevated to a guarantee of safety or confirmation of NR harm. - Application exceptions: Even if a signal without a denominator is added, do not convert it into an incidence rate; retain separate efficacy and harm statuses. - Remaining uncertainty: Event frequency or causality cannot be assessed because records are absent for event definitions, systematic/spontaneous collection, exposure denominators, temporal order, discontinuation/recovery, between-arm comparisons, other causes, and missing data. - Referenced methods: M19 §19.1.2–19.2.4; internal application / M19 §19.1.2–19.2.4; detailed distinctions are internally designed / M19 §19.2 harm questions by study design; details of temporal relationships are internally designed / M19 §19.2.2–19.2.4, M03 §3.2.3; internal application / M19 §19.2.2–19.2.4 design considerations; detailed confounding records are internally designed / M19 §19.1.2–19.2.4, M04 §4.6.3; internal application / Chamgap’s own interpretive boundary. References M19 principles; not an application of an official causality tool - Related sources: S01, S02 ### N34 · Does EFSA’s assessment of specified NR chloride for use at 300 mg/day in healthy adults guarantee safety for the target question? Verification status: Not met Reading scope: The native summaries and values in the retained manuscript were read. External papers, official documents, and registrations remain unread in the current review. - Current findings: S11/S12 are official safety and use assessments of specified NR chloride. Assessment of use at 300 mg/day in healthy adults is neither a safety guarantee for this frail population’s plan of 2,000 mg/day for 52 weeks nor approval of walking efficacy. - Why unverified: The populations, substances, and conditions of use in the official materials are not equivalent to direct safety information for the target plan. The manuscript also did not copy nicotinic-acid flushing or hepatic harm to NR. - Reason for missing information: The populations, substances, and conditions of use in the official materials are not equivalent to direct safety information for the target plan. The manuscript also did not copy nicotinic-acid flushing or hepatic harm to NR. - Required materials and conditions: The substance, use amount, population, and duration in the EFSA assessment, and direct safety data from the target trial - Materials to obtain first: The substance, use amount, population, and duration in the EFSA assessment, and direct safety data from the target trial - Further research: Separately review long-term safety follow-up appropriate to the target product, dose, and frail population, along with data on concomitant treatments and vulnerable groups. - Conditions for verification: State the scope of the official use assessment, and do not transfer assessments of different substances, doses, or populations to the overall safety of the target plan. - Why this condition is needed: Needed to avoid extending the authority of an official assessment to a guarantee of safety for all other exposures. - Application exceptions: Official documents are not independent new events or trials; do not double-count safety data they cite again. Do not use a use assessment as personal dosing instructions. - Remaining uncertainty: The populations, substances, and conditions of use in the official materials are not equivalent to direct safety information for the target plan. The manuscript also did not copy nicotinic-acid flushing or hepatic harm to NR. - Referenced methods: M19 §19.1.2–19.2.4; internal application / M04 §4.6.1–4.6.2; adaptations of harm data are internally designed / Chamgap’s own interpretive boundary. References M19 principles; not an application of an official causality tool - Related sources: S11, S12 ### N35 · Are arm-specific changes in medicines, diet, exercise, rehabilitation, and dose reduction/discontinuation verified? Verification status: Unverified Reading scope: The native summaries and values in the retained manuscript were read. External papers, official documents, and registrations remain unread in the current review. - Current findings: Policies for common medicines, diet, exercise, and rehabilitation in both arms, and actual dosing frequency, dose escalation, adherence, and changes, are unverified. Do not attribute effects of other medicines or rehabilitation to NR. - Why unverified: The full registration and actual implementation records have not been verified, so the effects of concurrent changes and discontinuations cannot be assessed. Do not fill these gaps with an absence of concomitant treatment or completed medication use. - Reason for missing information: The full registration and actual implementation records have not been verified, so the effects of concurrent changes and discontinuations cannot be assessed. Do not fill these gaps with an absence of concomitant treatment or completed medication use. - Required materials and conditions: Lists and timing of concomitant treatments in both arms, medication adherence, dose reduction/discontinuation, rescue treatment, and analytical handling - Materials to obtain first: Lists and timing of concomitant treatments in both arms, medication adherence, dose reduction/discontinuation, rescue treatment, and analytical handling - Further research: Collect the timing of medication changes and concurrent treatments, and explicitly distinguish the effect of assignment, the effect of adherence, and attribution of harms. - Conditions for verification: Connect differences in actual exposure and concurrent treatments to interpretation of results and safety, and do not confirm actual implementation from planned rules alone. - Why this condition is needed: Concurrent exposures, selection, and losses must be distinguished when attributing the actual effect of interest and harms. - Application exceptions: Do not exclude solely because concomitant treatment is present; compare differences between arms, the contrast of interest, and handling methods. - Remaining uncertainty: The full registration and actual implementation records have not been verified, so the effects of concurrent changes and discontinuations cannot be assessed. Do not fill these gaps with an absence of concomitant treatment or completed medication use. - Referenced methods: M03 §3.2.3, M08 §8.2.2–8.2.3; internal application / M19 §19.2.2–19.2.4 design considerations; detailed confounding records are internally designed / M19 §19.1.2–19.2.4, M04 §4.6.3; internal application - Related sources: S01, S02 ### N36 · Does the claim also extend to the optimal dose, maintenance after discontinuation, and effects in other frailty strata? Verification status: Not applicable Reading scope: The native summaries and values in the retained manuscript were read. External papers, official documents, and registrations remain unread in the current review. - Current findings: The current table concerns usual speed under the planned conditions of 2,000 mg/day, 52 weeks, and Fried≥3. It does not establish the optimal dose, persistence after discontinuation, or effects across all frailty strata at the same time. - Why unverified: Extended claims are outside the scope of this independent question. Not applicable does not mean that those extended effects are absent or that external full text has been read. - Reason for missing information: Extended claims are outside the scope of this independent question. Not applicable does not mean that those extended effects are absent or that external full text has been read. - Required materials and conditions: Direct dose comparisons, follow-up after discontinuation, and prespecified subgroup/interaction data needed when making such extended claims - Materials to obtain first: Direct dose comparisons, follow-up after discontinuation, and prespecified subgroup/interaction data needed when making such extended claims - Further research: If a new extension question is requested, first define separate questions and plans for dose comparisons, follow-up after discontinuation, and effect modification. - Conditions for verification: Separate the narrow planned contrast from effects at other doses, after discontinuation, and in subgroups; do not require extension trials unnecessary for the current question. - Why this condition is needed: A boundary condition to prevent a narrow result from being extended to optimal treatment, maintenance, or all subgroups. - Application exceptions: Actual 52-week results for the original question are needed. Separate evidence of maintenance effects after discontinuation is not imposed as a mandatory requirement for this table. - Remaining uncertainty: Extended claims are outside the scope of this independent question. Not applicable does not mean that those extended effects are absent or that external full text has been read. - Referenced methods: M03 §3.2.1–3.2.4; details on dose, persistence, and effect modification are internally designed - Related sources: S01, S02 ### N37 · Does the claim also encompass prevention of falls, hospitalization, and death, and improvement in quality of life? Verification status: Not applicable Reading scope: The native summaries and values in the retained manuscript were read. External papers, official documents, and registrations remain unread in the current review. - Current findings: The original question concerns usual walking function itself. Prevention of falls, hospitalization, and death, and improvement in quality of life are not adjudicated together with it. - Why unverified: Separate clinical events are outside the fixed question. This boundary of non-applicability does not imply an absence of effects on those events, nor does it remove the necessary conditions for the current speed outcome. - Reason for missing information: Separate clinical events are outside the fixed question. This boundary of non-applicability does not imply an absence of effects on those events, nor does it remove the necessary conditions for the current speed outcome. - Required materials and conditions: Event definitions, observation windows, comparison denominators, and direct estimation data required when making claims about those events - Materials to obtain first: Event definitions, observation windows, comparison denominators, and direct estimation data required when making claims about those events - Further research: If event prevention becomes a new question, a design with definitions, follow-up, denominators, and comparisons for those events is reviewed separately. - Conditions for verification: Direct evidence on other clinical events and quality of life is addressed separately from the usual-speed question. - Why this condition is needed: This is needed to prevent a functional-measurement question from automatically being extended to prevention of separate events. - Application exceptions: A mortality trial is not uniformly required for a question about change in usual speed itself. If the claim is extended, separate direct-evidence conditions are fixed. - Remaining uncertainty: Separate clinical events are outside the fixed question. This boundary of non-applicability does not imply an absence of effects on those events, nor does it remove the necessary conditions for the current speed outcome. - Referenced methods: M03 §3.2.4; internally designed boundaries for extensions / M03 §3.1, §3.2.1–3.2.4 principles for clarifying the question; detailed separation rules are internally designed - Related sources: ### N38 · Do 0 direct results and no_human_study mean that all human NR research amounts to 0? Verification status: Verified Reading scope: The native summaries and values in the retained manuscript were read. External papers, official documents, and registrations remain unread in the current review. - Current findings: In the logged search as of 2026-09-15, no directly eligible result for the fixed question was verified; that is the meaning of the original 0. human_NR_trials_exist=true and no_human_study=true coexist; the latter has the narrow meaning of a gate for calculator compatibility. - Why unverified: The original grade_semantics specifies the scope. The original ? and null score are preserved, without carrying them over as this table's verification status, an efficacy probability, or a new judgment. - Reason for missing information: The original grade_semantics specifies the scope. The original ? and null score are preserved, without carrying them over as this table's verification status, an efficacy probability, or a new judgment. - Required materials and conditions: The original search reference date, selection records, and explicit scope within which directly eligible results were checked - Materials to obtain first: The original search reference date, selection records, and explicit scope within which directly eligible results were checked - Further research: Future evidence updates retain the same boundaries, search dates, and eligibility records, and distinguish new results from existing plans and other outcomes. - Conditions for verification: The scope of the original 0 and the compatibility boolean is preserved, without extending it to 0 effect, 0 human studies, or worldwide absence. - Why this condition is needed: This is needed so that the different meanings of the numeric value 0 and the historical boolean do not produce a false declaration of absence. - Application exceptions: The original log files and ZIP were not opened this time, so the search as of the reference date is neither rerun nor presented as a current, up-to-date comprehensive review. - Remaining uncertainty: The original grade_semantics specifies the scope. The original ? and null score are preserved, without carrying them over as this table's verification status, an efficacy probability, or a new judgment. - Referenced methods: M04 §4.5, §4.6.3; limits on the current data transformation follow the user's scope and internal design / M03 §3.1, §3.2.1–3.2.4 principles for clarifying the question; detailed separation rules are internally designed - Related sources: ### N39 · Are the currently preserved archived summaries distinguished from external access and full-text reading at that earlier time? Verification status: Verified Reading scope: The native summaries and values in the retained manuscript were read. External papers, official documents, and registrations remain unread in the current review. - Current findings: This time, the entire KO/EN text, structure, bibliography, and history of the preserved archived summaries, identical to the current source, were read. Report-specific access records dated 2026-09-15 for official indexes, application shells, abstracts, figure legends, HTML, and correction metadata are historical records. External materials have not been accessed or read this time; access has not been attempted. - Why unverified: The scope of the current summary reading and the attribution of the historical access descriptions were checked. The existence of publisher, PMC, and official links is distinguished from having read the full text now. - Reason for missing information: The scope of the current summary reading and the attribution of the historical access descriptions were checked. The existence of publisher, PMC, and official links is distinguished from having read the full text now. - Required materials and conditions: Each report's actual material type, original address, current access-not-attempted/unread status, historical access_level/date, and original location - Materials to obtain first: Each report's actual material type, original address, current access-not-attempted/unread status, historical access_level/date, and original location - Further research: When materials are acquired, their original locations, access events, dates, and material types are recorded by report, and original summaries are distinguished from directly obtained full texts. This is a method for reviewing materials, separate from a clinical trial proposal. - Conditions for verification: Reading the local summaries now is not presented as current reading of external abstracts, full texts, or registrations; historical access levels are kept separate for each report. - Why this condition is needed: This is needed to avoid confusing links, historical access records, and local summaries with current full-text reading. - Application exceptions: Current access that was not attempted is not labeled as failed. A historical description of full-text access is not copied to another material type for the same article. - Remaining uncertainty: The scope of the current summary reading and the attribution of the historical access descriptions were checked. The existence of publisher, PMC, and official links is distinguished from having read the full text now. - Referenced methods: M04 §4.5–4.6 principles for data collection/selection; the separation of access from reading and the hyperlink contract are internally designed / M04 §4.5, §4.6.3; limits on the current data transformation follow the user's scope and internal design - Related sources: S01, S02, S03, S04, S05, S08, S09, S10, S11, S12, S13, S14, S15, S17, S18 ### N40 · Were the original ?, null values, axes, calculations, and publication metadata preserved without a new judgment? Verification status: Verified Reading scope: The native summaries and values in the retained manuscript were read. External papers, official documents, and registrations remain unread in the current review. - Current findings: Record from the time the preservation table was prepared: The original grade ?, null score, B/P, unscored axes, compatibility boolean, 4 historical arithmetic calculations, document self-review, and publication reference date are preserved. In that record, the original deployed_at was null, and the map current at that time was also not publicly deployed. - Why unverified: Preservation of the original values is neither a new efficacy judgment nor document-quality certification. The preserved arithmetic was performed at that earlier time; no new clinical calculations were performed this time. - Reason for missing information: Preservation of the original values is neither a new efficacy judgment nor document-quality certification. The preserved arithmetic was performed at that earlier time; no new clinical calculations were performed this time. - Required materials and conditions: The exact original values for the original judgment, unscored axes, historical arithmetic, document quality, and manuscript publication/deployment metadata - Materials to obtain first: The exact original values for the original judgment, unscored axes, historical arithmetic, document quality, and manuscript publication/deployment metadata - Further research: Future updates preserve the source bytes before and after changes and the reasons for changes, and distinguish changes in conditions, additions of materials, and new publication events. - Conditions for verification: Native typed values and historical records are preserved in their original form, without elevating them to new efficacy or safety grades, check scores, or completed publication. - Why this condition is needed: This is needed to prevent the status of the table conversion from being misread as an existing grade, a calculated value, or a public publication event. - Application exceptions: Values, grades, and reading scopes from other current judgments are not carried over to this table. The original ? is not used as a simple substitute label for unread materials. - Remaining uncertainty: Preservation of the original values is neither a new efficacy judgment nor document-quality certification. The preserved arithmetic was performed at that earlier time; no new clinical calculations were performed this time. - Referenced methods: M04 §4.5, §4.6.3; limits on the current data transformation follow the user's scope and internal design / M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses is internally designed - Related sources: ## Evidence and sources ### S01 NADage investigators' web description of the plan [Source](https://www.helse-bergen.no/en/neuro-sysmed-english/clinical-studies-at-neuro-sysmed/dementia---clinical-studies/the-nadage-study/) Materials actually read: The corresponding Korean and English summaries and bibliographic records in the archived manuscript were read. The linked external source materials have not been read this time. Findings recorded in the summary: This describes the planned population, 2,000 mg/day, 52 weeks, and the 6-minute walk/sensors. It is not an actual result for the target usual speed. Record level: This is content recorded in the archived manuscript. It is not the result of a new comparison against external source materials this time. Independent replication: This report is linked to family F01. The number of independent replications for this question is unverified. | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Full text of a web document | Currently unverified | Not attempted this time | Unread | Historical access date for this material: 2026-09-15; recorded level: historical public description of the plan. This time, only the archived summaries were read; external access was not attempted, and the external materials were neither acquired nor read. | ### S02 NADage official registry index/application shell [Source](https://clinicaltrials.gov/study/NCT06208527) Materials actually read: The corresponding Korean and English summaries and bibliographic records in the archived manuscript were read. The linked external source materials have not been read this time. Findings recorded in the summary: Only the age/Fried criteria and placebo design from the official index are recorded. The full registration, its history, and posted results were not acquired at that time. Record level: This is content recorded in the archived manuscript. It is not the result of a new comparison against external source materials this time. Independent replication: This report is linked to family F01. The number of independent replications for this question is unverified. | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Full registry document | Currently unverified | Not attempted this time | Unread | Historical access date for this material: 2026-09-15; recorded level: historical official index, body text not acquired. This time, only the archived summaries were read; external access was not attempted, and the external materials were neither acquired nor read. | ### S03 NR-VETS official registry index [Source](https://clinicaltrials.gov/study/NCT04691986) Materials actually read: The corresponding Korean and English summaries and bibliographic records in the archived manuscript were read. The linked external source materials have not been read this time. Findings recorded in the summary: This is a limited index of the official title and walking description. The full hierarchy, latest status, and target results are unverified. Record level: This is content recorded in the archived manuscript. It is not the result of a new comparison against external source materials this time. Independent replication: This report is linked to family F02. The number of independent replications for this question is unverified. | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Full registry document | Currently unverified | Not attempted this time | Unread | Historical access date for this material: 2026-09-15; recorded level: historical official index, body text not acquired. This time, only the archived summaries were read; external access was not attempted, and the external materials were neither acquired nor read. | ### S04 NR-VETS institutional recruitment index [Source](https://www.kumc.edu/research/landon-center-on-aging/research/information-for-research-volunteers/explore-study-opportunities.html) Materials actually read: The corresponding Korean and English summaries and bibliographic records in the archived manuscript were read. The linked external source materials have not been read this time. Findings recorded in the summary: The population in the institutional index has Fried<3. It does not match the target frailty criterion, and the complete current materials are unverified. Record level: This is content recorded in the archived manuscript. It is not the result of a new comparison against external source materials this time. Independent replication: This report is linked to family F02. The number of independent replications for this question is unverified. | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Full text of a web document | Currently unverified | Not attempted this time | Unread | Historical access date for this material: 2026-09-15; recorded level: historical official index, body text not acquired. This time, only the archived summaries were read; external access was not attempted, and the external materials were neither acquired nor read. | ### S05 Orr MCI abstract, bibliography, and figure legends [Source](https://pubmed.ncbi.nlm.nih.gov/37994989/) Materials actually read: The corresponding Korean and English summaries and bibliographic records in the archived manuscript were read. The linked external source materials have not been read this time. Findings recorded in the summary: These are within-group p-values for walking in MCI. The 20 completers are not the analysis n for the target usual speed, nor is this a between-group estimate in m/s. Record level: This is content recorded in the archived manuscript. It is not the result of a new comparison against external source materials this time. Independent replication: This report is linked to family F03. The number of independent replications for this question is unverified. | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Article abstract and bibliography | Currently unverified | Not attempted this time | Unread | Historical access date for this material: 2026-09-15; recorded level: historical abstract, bibliography, and figure legends. This time, only the archived summaries were read; external access was not attempted, and the external materials were neither acquired nor read. | | Full text of a clinical research article | Direct full-text URL not acquired; bibliographic lead available | Not attempted this time | Unread | No direct URL for this clinical article's full text has been acquired, and no historical record of accessing its full text is available. The DOI is a bibliographic lead. This time, external full-text access was not attempted, and the full text was neither acquired nor read. | ### S08 Martens crossover article in healthy participants [Source](https://www.nature.com/articles/s41467-018-03421-7) Materials actually read: The corresponding Korean and English summaries and bibliographic records in the archived manuscript were read. The linked external source materials have not been read this time. Findings recorded in the summary: The study reported no overall improvement in motor function in healthy participants. The supplementary figures and usual-speed values were not extracted, and this finding is not transferred as refutation of the target effect in frailty. Record level: This is content recorded in the archived manuscript. It is not the result of a new comparison against external source materials this time. Independent replication: This report is linked to family F04. The number of independent replications for this question is unverified. | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Full text of a clinical research article | Currently unverified | Not attempted this time | Unread | Historical access date for this material: 2026-09-15; recorded level: historical HTML full text. This time, only the archived summaries were read; external access was not attempted, and the external materials were neither acquired nor read. | ### S09 NICE PAD article [Source](https://www.nature.com/articles/s41467-024-49092-5) Materials actually read: The corresponding Korean and English summaries and bibliographic records in the archived manuscript were read. The linked external source materials have not been read this time. Findings recorded in the summary: The 6-month between-group 6MWD result in PAD of +17.6 m, one-sided 90% CI [+1.77,+∞) m, p=0.08 is a positive adjacent finding. It is not a result for the target usual speed in m/s. Record level: This is content recorded in the archived manuscript. It is not the result of a new comparison against external source materials this time. Independent replication: This report is linked to family F05. The number of independent replications for this question is unverified. | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Full text of a clinical research article | Currently unverified | Not attempted this time | Unread | Historical access date for this material: 2026-09-15; recorded level: historical HTML full text. This time, only the archived summaries were read; external access was not attempted, and the external materials were neither acquired nor read. | ### S10 NICE publisher correction [Source](https://www.nature.com/articles/s41467-024-51289-7) Materials actually read: The corresponding Korean and English summaries and bibliographic records in the archived manuscript were read. The linked external source materials have not been read this time. Findings recorded in the summary: Only the existence and identifier of the correction were verified at that time. The content of the correction and its impact on the effect are unverified. Record level: This is content recorded in the archived manuscript. It is not the result of a new comparison against external source materials this time. Independent replication: This report is linked to family F05. The number of independent replications for this question is unverified. | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Full text of a correction | Currently unverified | Not attempted this time | Unread | Historical access date for this material: 2026-09-15; recorded level: historical bibliographic verification, failed access to the body text. This time, only the archived summaries were read; external access was not attempted, and the external materials were neither acquired nor read. | ### S11 EFSA 2019 NR chloride safety assessment [Source](https://www.efsa.europa.eu/en/efsajournal/pub/5775) Materials actually read: The corresponding Korean and English summaries and bibliographic records in the archived manuscript were read. The linked external source materials have not been read this time. Findings recorded in the summary: This assesses use of a specified substance in healthy people. It does not guarantee 52-week safety at a high dose in frail participants or efficacy for walking. Record level: This is content recorded in the archived manuscript. It is not the result of a new comparison against external source materials this time. Independent replication: This report is linked to family REG-EFSA-2019. The number of independent replications for this question is unverified. | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Full text of an official web document | Currently unverified | Not attempted this time | Unread | Historical access date for this material: 2026-09-15; recorded level: historical HTML full text. This time, only the archived summaries were read; external access was not attempted, and the external materials were neither acquired nor read. | ### S12 EFSA 2021 assessment of extended uses of NR chloride [Source](https://www.efsa.europa.eu/en/efsajournal/pub/6843) Materials actually read: The corresponding Korean and English summaries and bibliographic records in the archived manuscript were read. The linked external source materials have not been read this time. Findings recorded in the summary: This is an official opinion for specified conditions of use. Those NR chloride conditions are not extrapolated to long-term safety at the target high dose. Record level: This is content recorded in the archived manuscript. It is not the result of a new comparison against external source materials this time. Independent replication: This report is linked to family REG-EFSA-2021. The number of independent replications for this question is unverified. | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Full text of an official web document | Currently unverified | Not attempted this time | Unread | Historical access date for this material: 2026-09-15; recorded level: historical HTML full text. This time, only the archived summaries were read; external access was not attempted, and the external materials were neither acquired nor read. | ### S13 Identification of an article on other NAD precursors [Source](https://pmc.ncbi.nlm.nih.gov/articles/PMC8485915/) Materials actually read: The corresponding Korean and English summaries and bibliographic records in the archived manuscript were read. The linked external source materials have not been read this time. Findings recorded in the summary: This is identity screening for tryptophan, nicotinic acid, and NAM. These are not NR, and no numbers were newly extracted or reassessed. Record level: This is content recorded in the archived manuscript. It is not the result of a new comparison against external source materials this time. Independent replication: This report is linked to family ADJ-CONNELL. The number of independent replications for this question is unverified. | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Full text of a clinical research article | Currently unverified | Not attempted this time | Unread | Historical access date for this material: 2026-09-15; recorded level: historical bibliographic index of the original article. This time, only the archived summaries were read; external access was not attempted, and the external materials were neither acquired nor read. | ### S14 Identification of an NMN article in healthy older men [Source](https://www.nature.com/articles/s41514-022-00084-z) Materials actually read: The corresponding Korean and English summaries and bibliographic records in the archived manuscript were read. The linked external source materials have not been read this time. Findings recorded in the summary: NMN is not NR. Positive walking data are not transferred to the target molecule. Record level: This is content recorded in the archived manuscript. It is not the result of a new comparison against external source materials this time. Independent replication: This report is linked to family ADJ-IGARASHI. The number of independent replications for this question is unverified. | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Full text of a clinical research article | Currently unverified | Not attempted this time | Unread | Historical access date for this material: 2026-09-15; recorded level: historical HTML title-and-abstract screening. This time, only the archived summaries were read; external access was not attempted, and the external materials were neither acquired nor read. | ### S15 Publisher abstract on NR+exercise in hypertension [Source](https://link.springer.com/article/10.1007/s11357-025-01815-2) Materials actually read: The corresponding Korean and English summaries and bibliographic records in the archived manuscript were read. The linked external source materials have not been read this time. Findings recorded in the summary: This is screening material on a combined intervention involving exercise in hypertension. It is not a direct replication for usual speed in frailty. Record level: This is content recorded in the archived manuscript. It is not the result of a new comparison against external source materials this time. Independent replication: This report is linked to family ADJ-LIN. The number of independent replications for this question is unverified. | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Article abstract and bibliography | Currently unverified | Not attempted this time | Unread | Historical access date for this material: 2026-09-15; recorded level: historical publisher abstract and later sections. This time, only the archived summaries were read; external access was not attempted, and the external materials were neither acquired nor read. | | Full text of a clinical research article | Direct full-text URL not acquired; bibliographic lead available | Not attempted this time | Unread | No direct URL for this clinical article's full text has been acquired, and no historical record of accessing its full text is available. The DOI is a bibliographic lead. This time, external full-text access was not attempted, and the full text was neither acquired nor read. | ### S17 NICE-FIT official registry title [Source](https://clinicaltrials.gov/study/NCT06465602) Materials actually read: The corresponding Korean and English summaries and bibliographic records in the archived manuscript were read. The linked external source materials have not been read this time. Findings recorded in the summary: The substance in the title is nicotinamide. NR identity, product, and results are unverified, so this is not used as direct NR evidence. Record level: This is content recorded in the archived manuscript. It is not the result of a new comparison against external source materials this time. Independent replication: This report is linked to family ADJ-NICE-FIT. The number of independent replications for this question is unverified. | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Full registry document | Currently unverified | Not attempted this time | Unread | Historical access date for this material: 2026-09-15; recorded level: historical official index title. This time, only the archived summaries were read; external access was not attempted, and the external materials were neither acquired nor read. | ### S18 Identification of an article on a combination intervention and cognition in older dogs [Source](https://www.nature.com/articles/s41598-024-63031-w) Materials actually read: The corresponding Korean and English summaries and bibliographic records in the archived manuscript were read. The linked external source materials have not been read this time. Findings recorded in the summary: The species, intervention, and endpoint do not match: older dogs, a combination product, and owner assessments of cognition. Effect estimates in dogs were not used. Record level: This is content recorded in the archived manuscript. It is not the result of a new comparison against external source materials this time. Independent replication: This report is linked to family ADJ-DOG. The number of independent replications for this question is unverified. | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Full text of a nonhuman research article | Currently unverified | Not attempted this time | Unread | Historical access date for this material: 2026-09-15; recorded level: historical HTML title-and-abstract screening. This time, only the archived summaries were read; external access was not attempted, and the external materials were neither acquired nor read. | ## Review criteria and methods These are Chamgap's own application conditions, informed by the relevant sections of official methodological guidance. They do not constitute official assessment-tool certification or a new efficacy score. - M03 [Cochrane Handbook 6.5 (2024), chapter updated 2023-08](https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-03) · §3.1, §3.2.1–3.2.3, MECIR C5/C7/C13 · Clearly record the question, eligibility conditions, and reasons for changes, and distinguish variations in interventions. · Reuse of actual original-byte/SHA copies of the methodological files preserved from the 1585 pilot. The full methodological texts were not newly read this time, nor were the official methods implemented in full. - M04 [Cochrane Handbook 6.5.1 (2025), chapter updated 2025-03](https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-04) · §4.5, §4.6.1–4.6.3, MECIR C42 · Distinguish studies from reports and link them; do not exclude a study solely because its results are unreported. · Reuse of actual original-byte/SHA copies of the methodological files preserved from the 1585 pilot. The full methodological texts were not newly read this time, nor were the official methods implemented in full. - M08 [Cochrane Handbook 6.5 (2024), chapter updated 2019-10](https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-08) · §8.1–8.2.3, Table 8.2.a · Fix the outcome and effect of interest when reviewing randomization, deviations, missingness, measurement, and selective reporting. · Reuse of actual original-byte/SHA copies of the methodological files preserved from the 1585 pilot. The full methodological texts were not newly read this time, nor were the official methods implemented in full. - 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. Precision is not determined by sample size alone. · Reuse of actual original-byte/SHA copies of the methodological files preserved from the 1585 pilot. The full methodological texts were not newly read this time, nor were the official methods implemented in full. - 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 that differ from those for efficacy. Case reports do not establish incidence rates. · Reuse of actual original-byte/SHA copies of the methodological files preserved from the 1585 pilot. The full methodological texts were not newly read this time, nor were the official methods implemented in full. ## What the statuses mean - Verified: Verification of the stated question and boundaries in the preserved materials; not confirmation of efficacy or safety. - Partly verified: Only some information has been verified; the full set of necessary conditions remains unverified. - Unverified: Direct materials, methods, and results within the scope of the current input are unverified. This does not mean that studies are absent or that the intervention is ineffective. - Not met: The actual population, endpoint, or exposure in the materials does not match the fixed question. This is not a judgment of efficacy failure. - Not applicable: An extension condition outside the narrow question. This status must not be used in place of recording that a full text has not been read. ## Change history 2026-11-01 · Public page/materials 1.0. Public-facing display and data were created from the existing 40 items. No new clinical searches, changes in verification status, or scoring were performed.