# Oral single-active-ingredient pantothenic acid (vitamin B5) supplementation × Reduction in LDL-C concentration in adults with elevated LDL-C Verdict 3100 · Evidence Check Stored-material review date: 2026-10-05 Original evidence date: 2026-09-15 Review-criteria version: NGM-v3100-SOLE-ORAL-B5-ELEVATED-LDL-C-1.0 Public page/material preparation date: 2026-11-02 Clinical papers were not read directly; existing review summaries were checked. No new clinical-literature search was performed. Unverified does not mean that research is absent or that there is no effect. ## Assessment scope - Population: Adults with elevated LDL-C; actual diagnostic criteria, baseline values, medications, and deficiency status unverified - Ingredient, formulation and route: Pantothenic acid (vitamin B5) as the sole active ingredient; calcium salt to be verified separately · Oral product with a single active ingredient; exact salt, tablet/capsule, and release type unverified - Dose: Unverified — eligible pantothenic-acid monotherapy dose and frequency not verified - Comparator: Placebo or usual care on the same background treatment; actual composition and shared treatment unverified - Measured outcome: Between-group difference in change in LDL-C concentration (mg/dL or mmol/L); endpoint difference separate, actual eligible results unverified - Duration: Unverified — eligible monotherapy treatment duration and time points not verified - Questions outside this scope: Extensions to pantethine/pantetheine/other molecules, B-complex products, nonhuman mechanisms, skin/hair/acne, LDL oxidative stability, cardiovascular events/replacement of lipid-lowering medication, optimal dose/persistence, and all populations are separate. ## Checklist items ### N01 · Which ingredient, population, and LDL-C comparison? Verification status: Met Reading scope: The complete, exactly retained archived summary was actually read; the linked original material was not read in this review - Current findings: The selected question is whether oral treatment with pantothenic acid as the sole active ingredient lowers LDL-C concentration more than placebo or usual care on the same background treatment in adults with elevated LDL-C. subclaims is an empty list. - Why unverified: This verifies the identity of the question, not direct efficacy. - Reason for missing information: This verifies the identity of the question, not direct efficacy. - Required materials and conditions: Adults with elevated LDL-C, oral B5 monotherapy, comparator with the same background treatment, between-group change in LDL-C - Materials to obtain first: Adults with elevated LDL-C, oral B5 monotherapy, comparator with the same background treatment, between-group change in LDL-C - Further research: Compare differences in ingredient, population, endpoint, and comparison between the existing question and candidate results for each material. - Conditions for verification: Link the current original effect wording and inclusion/exclusion boundaries to exact locations. - Why this condition is needed: Needed to avoid combining all lipid-related efficacy claims for the ingredient into a single question. - Application exceptions: Pantethine, multicomponent products, acne, and clinical events are separate questions. - Remaining uncertainty: This verifies the identity of the question, not direct efficacy. - Referenced methods: Question-clarification principles in M03 §3.1, §3.2.1–3.2.4; detailed separation rules are internally designed; M03 §3.2.1; detailed population conditions are internally designed; M03 §3.2.2–3.2.3; reverse-direction labeling and adaptation to laboratory tests are internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed - Related sources: S101, S105 ### N02 · Are pantothenic acid and pantethine the same intervention? Verification status: Met Reading scope: The complete, exactly retained archived summary was actually read; the linked original material was not read in this review - Current findings: Pantethine is a different substance from pantothenic acid. pantetheine, dexpanthenol/panthenol, and B-complex products were distinguished from the direct intervention, and the exact identity of the calcium salt remained unverified. - Why unverified: Verifying the substance boundary is separate from verifying the specifications of an eligible product. - Reason for missing information: Verifying the substance boundary is separate from verifying the specifications of an eligible product. - Required materials and conditions: Exact molecule, salt, active ingredient, and route of administration - Materials to obtain first: Exact molecule, salt, active ingredient, and route of administration - Further research: Compare product composition and chemical-form documents for each result to verify whether the active ingredient is the same. - Conditions for verification: Link differences in substance, combination, and route to the original text and explain the limits of direct attribution. - Why this condition is needed: Needed to avoid transferring clinical results solely on the basis of a description as a derivative. - Application exceptions: Verify the exact salt of calcium pantothenate separately and perform no new mass conversion. - Remaining uncertainty: Verifying the substance boundary is separate from verifying the specifications of an eligible product. - Referenced methods: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptation to laboratory tests are internally designed; M03 §3.2.3, M08 §8.2.2–8.2.3; internal application - Related sources: S101, S06, L028 ### N03 · Are the origin, salt, and formulation of an eligible single-active-ingredient product known? Verification status: Unverified Reading scope: The complete, exactly retained archived summary was actually read; the linked original material was not read in this review - Current findings: The origin, brand, salt, purity, batch, formulation, and release type of an eligible pantothenic-acid single-active-ingredient product are unverified. - Why unverified: Specifications not supplied by the current material were not taken from related products. - Reason for missing information: Specifications not supplied by the current material were not taken from related products. - Required materials and conditions: Manufacturing origin, brand, exact salt, purity, batch, tablet/capsule, and release type - Materials to obtain first: Manufacturing origin, brand, exact salt, purity, batch, tablet/capsule, and release type - Further research: Verify formulation analysis, batch, and composition materials by linking them to actual comparative trial results. - Conditions for verification: Distinguish verified values for a directly eligible formulation from unverified product items. - Why this condition is needed: Needed to avoid inserting the specifications of another molecule or multicomponent product into those of the directly relevant product. - Application exceptions: An oral single-active-ingredient product specified in the question is not an actual product specification. - Remaining uncertainty: Specifications not supplied by the current material were not taken from related products. - Referenced methods: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptation to laboratory tests are internally designed - Related sources: S101, S105 ### N04 · What are the actual dose and total exposure for B5 monotherapy? Verification status: Unverified Reading scope: The complete, exactly retained archived summary was actually read; the linked original material was not read in this review - Current findings: The pantothenic-acid monotherapy dose and frequency are unverified. Evans's initial 600 mg/day and later 900 mg/day are pantethine doses and were not transferred as B5 treatment doses. - Why unverified: No new calcium-salt mass conversion or personal dosage was created. - Reason for missing information: No new calcium-salt mass conversion or personal dosage was created. - Required materials and conditions: Single-active-ingredient dose, frequency, active amount, dietary/concurrent supplementation, and adherence - Materials to obtain first: Single-active-ingredient dose, frequency, active amount, dietary/concurrent supplementation, and adherence - Further research: Collect administration, composition, adherence, and dietary-exposure records by arm to examine actual differences in intervention. - Conditions for verification: Verify the directly eligible dose and actual total exposure, leaving unavailable values unfilled. - Why this condition is needed: Needed to avoid using the pantethine dose as a pantothenic-acid treatment dose. - Application exceptions: The 600/900 mg pantethine doses, nutritional reference values, and examples of high-dose harms are separate records. - Remaining uncertainty: No new calcium-salt mass conversion or personal dosage was created. - Referenced methods: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptation to laboratory tests are internally designed; M03 §3.2.3, M08 §8.2.2–8.2.3; internal application; M03 §3.2.1–3.2.4; details of dose, duration, and effect modification are internally designed - Related sources: S101, S06 ### N05 · Have the directly relevant treatment duration and assessment time points been verified? Verification status: Unverified Reading scope: The complete, exactly retained archived summary was actually read; the linked original material was not read in this review - Current findings: Eligible monotherapy treatment duration and LDL-C assessment time points are unverified. 16 weeks is the duration of the Evans pantethine trial. - Why unverified: Duration for a different molecule does not meet the selected comparison. - Reason for missing information: Duration for a different molecule does not meet the selected comparison. - Required materials and conditions: Single-active-ingredient administration duration, planned/actual LDL-C time points, and follow-up - Materials to obtain first: Single-active-ingredient administration duration, planned/actual LDL-C time points, and follow-up - Further research: Compare the plan, actual exposure, and time points in outcome tables to distinguish prespecified endpoints from follow-up. - Conditions for verification: Distinguish eligible single-active-ingredient durations and time points from the duration of a related trial. - Why this condition is needed: Needed to avoid using 16 weeks for another substance as a verified value for the single-active-ingredient treatment. - Application exceptions: Do not arbitrarily specify a universal minimum treatment duration. - Remaining uncertainty: Duration for a different molecule does not meet the selected comparison. - Referenced methods: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptation to laboratory tests are internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed; M08 Table 8.2.a, M04 §4.6.3; internal application - Related sources: S101, S105 ### N06 · How were adults with elevated LDL-C selected? Verification status: Unverified Reading scope: The complete, exactly retained archived summary was actually read; the linked original material was not read in this review - Current findings: The question was fixed to adults with elevated LDL-C, but the diagnostic threshold, baseline values, and selection criteria in directly relevant monotherapy trials are unverified. - Why unverified: The population of a related trial is attributed only to that trial. - Reason for missing information: The population of a related trial is attributed only to that trial. - Required materials and conditions: Diagnostic threshold, baseline LDL-C, age, inclusion/exclusion, and setting - Materials to obtain first: Diagnostic threshold, baseline LDL-C, age, inclusion/exclusion, and setting - Further research: Obtain recruitment and baseline tables and exclusion criteria, and compare them with the population in the selected question. - Conditions for verification: Explain the actual recruitment/diagnosis in directly eligible studies and what remains unverified. - Why this condition is needed: Needed to avoid mistaking the population label in the question for actual recruitment criteria. - Application exceptions: Do not transfer the cardiovascular-risk and statin-eligible population of a pantethine trial to the single-active-ingredient population. - Remaining uncertainty: The population of a related trial is attributed only to that trial. - Referenced methods: M03 §3.2.1; detailed population conditions are internally designed - Related sources: S101 ### N07 · Can lipid-lowering medications, diet, deficiency, and other supplementation be distinguished? Verification status: Unverified Reading scope: The complete, exactly retained archived summary was actually read; the linked original material was not read in this review - Current findings: Medication, deficiency, and dietary/concurrent-supplementation status in the directly eligible population are unverified. - Why unverified: The description of a diet-controlled pantethine study is not a concomitant-treatment condition in the selected B5 trial. - Reason for missing information: The description of a diet-controlled pantethine study is not a concomitant-treatment condition in the selected B5 trial. - Required materials and conditions: Arm-specific lipid-lowering medications, diet, deficiency/nutritional status, and concurrent supplementation - Materials to obtain first: Arm-specific lipid-lowering medications, diet, deficiency/nutritional status, and concurrent supplementation - Further research: Compare baseline nutrition, medications, diet, and records of arm-specific changes with analyses for each outcome. - Conditions for verification: Link the scope and limitations of baseline/concomitant-treatment verification in eligible single-active-ingredient studies. - Why this condition is needed: Needed to avoid using differences in background treatment and correction of deficiency as an additional B5 effect. - Application exceptions: If baseline deficiency is unverified, do not establish that deficiency is absent. - Remaining uncertainty: The description of a diet-controlled pantethine study is not a concomitant-treatment condition in the selected B5 trial. - Referenced methods: M03 §3.2.1; detailed population conditions are internally designed; M03 §3.2.3, M08 §8.2.2–8.2.3; internal application - Related sources: S101, S105 ### N08 · What are the placebo or usual care and the actual shared treatment? Verification status: Unverified Reading scope: The complete, exactly retained archived summary was actually read; the linked original material was not read in this review - Current findings: Placebo or usual care on the same background treatment is the comparison specified in the question; directly eligible comparator composition and shared treatment are unverified. - Why unverified: A comparison of two B-complex formulations is not a placebo comparison of B5 monotherapy. - Reason for missing information: A comparison of two B-complex formulations is not a placebo comparison of B5 monotherapy. - Required materials and conditions: Actual placebo composition, usual care, rescue treatment, and arm-specific changes - Materials to obtain first: Actual placebo composition, usual care, rescue treatment, and arm-specific changes - Further research: Link arm-specific prescriptions, comparator composition, rescue treatment/changes, and analysis plans to verify the scope of contribution. - Conditions for verification: Distinguish the actual comparison, differences other than the intervention, and their implications for analysis. - Why this condition is needed: Needed to avoid using the planned comparison as verification of the actual comparator arm. - Application exceptions: Do not require all changes in both arms to be identical; examine them in relation to the effect of interest. - Remaining uncertainty: A comparison of two B-complex formulations is not a placebo comparison of B5 monotherapy. - Referenced methods: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptation to laboratory tests are internally designed; M03 §3.2.3, M08 §8.2.2–8.2.3; internal application; M08 §8.2.2, M15 §15.3.1; internal application - Related sources: S101, S105, S106 ### N09 · Were directly measured LDL and formula-calculated LDL distinguished? Verification status: Unverified Reading scope: The complete, exactly retained archived summary was actually read; the linked original material was not read in this review - Current findings: There is no information to distinguish directly measured LDL from formula-calculated LDL, and measurement procedures in eligible monotherapy trials are unverified. - Why unverified: Measurement information or results were not filled in through unit conversion or graph reconstruction. - Reason for missing information: Measurement information or results were not filled in through unit conversion or graph reconstruction. - Required materials and conditions: LDL measurement method, specimen/blood collection, calculation formula, and arm-specific procedures - Materials to obtain first: LDL measurement method, specimen/blood collection, calculation formula, and arm-specific procedures - Further research: Compare measurement methods, calculation formulas, blood-collection conditions, and assessment procedures with each outcome table. - Conditions for verification: Explain the actual measurement conditions for eligible LDL-C results and the scope that cannot be verified. - Why this condition is needed: Needed to avoid establishing that values from different measurement methods represent the same endpoint. - Application exceptions: Do not convert other lipid markers or oxidative stability into LDL-C concentration. - Remaining uncertainty: Measurement information or results were not filled in through unit conversion or graph reconstruction. - Referenced methods: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed; M08 Table 8.2.a, M03 §3.2.4; internal application - Related sources: S101, S108 ### N10 · Are differences in change, endpoint differences, and percentages the same value? Verification status: Met Reading scope: The complete, exactly retained archived summary was actually read; the linked original material was not read in this review - Current findings: The question concerns the between-group difference in change in LDL-C concentration, with endpoint differences kept separate. Evans's -11%/+3% were distinguished as changes from each arm's baseline and were not converted into a pantothenic-acid concentration difference. - Why unverified: This verifies the distinction between measures; it does not mean that single-active-ingredient results were obtained. - Reason for missing information: This verifies the distinction between measures; it does not mean that single-active-ingredient results were obtained. - Required materials and conditions: LDL-C definition, units, baseline/change/endpoint values, and between-group/within-group distinctions - Materials to obtain first: LDL-C definition, units, baseline/change/endpoint values, and between-group/within-group distinctions - Further research: Link outcome definitions, analyses, units, and time points to the original tables and protocol, preserving each separately. - Conditions for verification: Separate the selected between-group change in concentration from the different measures in related reports. - Why this condition is needed: Needed to avoid converting within-group percentages into placebo-adjusted concentration differences. - Application exceptions: Perform no new conversion between mg/dL and mmol/L. - Remaining uncertainty: This verifies the distinction between measures; it does not mean that single-active-ingredient results were obtained. - Referenced methods: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed; M08 §8.2.2, M15 §15.3.1; internal application - Related sources: S101 ### N11 · What intervention effect does an eligible analysis estimate? Verification status: Unverified Reading scope: The complete, exactly retained archived summary was actually read; the linked original material was not read in this review - Current findings: Baseline, change, and endpoint values and actual between-group analyses for B5 monotherapy are unverified. - Why unverified: Do not fill a direct B5 estimate with related pantethine analyses. - Reason for missing information: Do not fill a direct B5 estimate with related pantethine analyses. - Required materials and conditions: Between-group/within-group, change/endpoint, adjustment, ITT/PP, and analysis population - Materials to obtain first: Between-group/within-group, change/endpoint, adjustment, ITT/PP, and analysis population - Further research: Compare the analysis plan with actual outcome tables to verify the effect of interest, adjustment, and denominators. - Conditions for verification: Explain how the actual effect definition in directly eligible results agrees with or differs from the question. - Why this condition is needed: Needed to avoid transferring different effect definitions into the same estimate. - Application exceptions: Do not assume ITT or an adjusted effect if no record is available. - Remaining uncertainty: Do not fill a direct B5 estimate with related pantethine analyses. - Referenced methods: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed; M08 §8.2.2, M15 §15.3.1; internal application - Related sources: S101 ### N12 · Are the directly relevant LDL-C effect, CI, and P value known? Verification status: Unverified Reading scope: The complete, exactly retained archived summary was actually read; the linked original material was not read in this review - Current findings: Within primary_effect, the records for mean_difference, confidence_interval, p_value, and analysis sample size are empty/not_verified. - Why unverified: This does not confirm an effect of 0, equivalence, or the absence of a directly relevant effect. - Reason for missing information: This does not confirm an effect of 0, equivalence, or the absence of a directly relevant effect. - Required materials and conditions: Eligible between-group effect, uncertainty interval, P value, and units - Materials to obtain first: Eligible between-group effect, uncertainty interval, P value, and units - Further research: Review estimates, intervals, variance, and denominators in eligible outcome tables by attributing them to the actual analyses. - Conditions for verification: Distinguish the unverified direct-effect fields from related results. - Why this condition is needed: Needed to avoid converting an unverified result into an effect of 0 or nonsignificance. - Application exceptions: Do not reconstruct pantethine results, other biomarkers, or graphs as a directly relevant effect. - Remaining uncertainty: This does not confirm an effect of 0, equivalence, or the absence of a directly relevant effect. - Referenced methods: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed; M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptations are internally designed; M15 §15.3.1–15.3.3; internal application - Related sources: S101, S105 ### N13 · How many participants were allocated, measured, analyzed, and completed, respectively? Verification status: Unverified Reading scope: The complete, exactly retained archived summary was actually read; the linked original material was not read in this review - Current findings: Arm-specific LDL-C analysis denominators and allocated/completed counts in eligible B5 monotherapy trials are unverified. - Why unverified: Denominators from related studies were not transferred, and no new missing counts or rates were calculated. - Reason for missing information: Denominators from related studies were not transferred, and no new missing counts or rates were calculated. - Required materials and conditions: Arm-specific allocation/analysis/completion for the single-active-ingredient treatment, missing data, and outcome-specific denominators - Materials to obtain first: Arm-specific allocation/analysis/completion for the single-active-ingredient treatment, missing data, and outcome-specific denominators - Further research: Compare participant flow, reasons for missing data, and outcome-specific analysis tables to verify denominators. - Conditions for verification: Distinguish directly relevant outcome-specific denominators from what remains unverified. - Why this condition is needed: Needed to avoid using related sample sizes as directly relevant LDL-C analysis denominators. - Application exceptions: 32 allocated and 24 completed are denominators from the pantethine trial. - Remaining uncertainty: Denominators from related studies were not transferred, and no new missing counts or rates were calculated. - Referenced methods: M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptations are internally designed; M08 §8.2.2, M15 §15.3.1; internal application; M15 §15.3.1–15.3.3; internal application - Related sources: S101, S102 ### N14 · Are the design, concealment, and blinding of the monotherapy comparison known? Verification status: Unverified Reading scope: The complete, exactly retained archived summary was actually read; the linked original material was not read in this review - Current findings: The related Evans pantethine study is a triple-blind trial, but the directly relevant design, allocation, concealment, and blinding for B5 monotherapy are unverified. - Why unverified: Do not label this as formal execution of RoB 2 or absence of bias. - Reason for missing information: Do not label this as formal execution of RoB 2 or absence of bias. - Required materials and conditions: Actual design, allocation/concealment, baseline balance, and assessment procedures - Materials to obtain first: Actual design, allocation/concealment, baseline balance, and assessment procedures - Further research: Obtain monotherapy methods, registration, and baseline/assessment materials and review them at the outcome level. - Conditions for verification: Link the actual design/assessment information and limitations of the directly selected results. - Why this condition is needed: Needed to avoid using a triple-blind label from a related study as a direct B5 bias assessment. - Application exceptions: Do not mark crossover or cluster designs as not applicable when the design is unverified. - Remaining uncertainty: Do not label this as formal execution of RoB 2 or absence of bias. - Referenced methods: M08 §8.1–8.2.3; internal application; M08 Table 8.2.a, M03 §3.2.4; internal application; M03 §3.2.1; detailed population conditions are internally designed - Related sources: S101, S102 ### N15 · Are adherence, rescue treatment, analysis populations, and missing-data handling known? Verification status: Unverified Reading scope: The complete, exactly retained archived summary was actually read; the linked original material was not read in this review - Current findings: Adherence to the single-active-ingredient product, withdrawals by arm, analysis populations, and handling of missing data are unverified. - Why unverified: Pantethine allocation/completion counts alone do not reveal how the selected results were handled. - Reason for missing information: Pantethine allocation/completion counts alone do not reveal how the selected results were handled. - Required materials and conditions: Actual intake, discontinuation, arm-specific changes, ITT/PP, and missing-data handling - Materials to obtain first: Actual intake, discontinuation, arm-specific changes, ITT/PP, and missing-data handling - Further research: Compare the analysis plan, administration records, and participant flow against the results tables to examine their impact. - Conditions for verification: Distinguish directly eligible information on adherence, withdrawals, and analysis from what remains unverified. - Why this condition is needed: Needed to avoid mixing the effect of assignment with before-and-after effects among adherent participants/completers. - Application exceptions: Do not arbitrarily fill in analysis methods absent from the original text. - Remaining uncertainty: Pantethine allocation/completion counts alone do not reveal how the selected results were handled. - Referenced methods: M03 §3.2.3, M08 §8.2.2–8.2.3; own application; M08 §8.2.2, M15 §15.3.1; own application; M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; adaptations by study design are this project's own design - Related sources: S101 ### N16 · What magnitudes of difference does the reported interval allow? Verification status: Unverified Reading scope: The complete, exactly retained archived summary was actually read; the linked original material was not read in this review - Current findings: The direct LDL-C CI, variance, and important-difference criterion are unverified, and the original precision axis is an unscored empty value. - Why unverified: Do not use an unverified interval to exclude an important effect or create a new grade. - Reason for missing information: Do not use an unverified interval to exclude an important effect or create a new grade. - Required materials and conditions: Direct effect/CI, variance, and a justified important difference - Materials to obtain first: Direct effect/CI, variance, and a justified important difference - Further research: Obtain the basis for importance appropriate to the endpoint/population and the actual reported interval separately, and compare them. - Conditions for verification: Explain the relationship between the reported interval and the importance criterion, or why it cannot be interpreted. - Why this condition is needed: Needed to avoid declaring sufficiency based only on sample size, statistical significance, or the number of trials. - Application exceptions: Do not arbitrarily adopt a common minimum sample size, duration, or MCID. - Remaining uncertainty: Do not use an unverified interval to exclude an important effect or create a new grade. - Referenced methods: M15 §15.3.1–15.3.3; own application; M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; adaptations by study design are this project's own design - Related sources: S101 ### N17 · What produced the LDL-C improvement in Evans? Verification status: Partly verified Reading scope: The complete, exactly retained archived summary was actually read; the linked original material was not read in this review - Current findings: In Evans, the 16-week pantethine-arm -11% and placebo-arm +3% are changes from each arm's baseline. The positive pantethine results were preserved but were not attributed to an effect of pantothenic acid as the sole active ingredient. - Why unverified: The complete original results tables and a single-active-ingredient B5 estimate are unverified in this review. - Reason for missing information: The complete original results tables and a single-active-ingredient B5 estimate are unverified in this review. - Required materials and conditions: Actual ingredients, within-arm changes, time points, and original tables from the pantethine trial - Materials to obtain first: Actual ingredients, within-arm changes, time points, and original tables from the pantethine trial - Further research: Compare the original LDL-C tables against the product/analysis documents to verify the scope of the reported values. - Conditions for verification: Explain the measure, duration, and substance in the positive report together with the reason for its direct ineligibility. - Why this condition is needed: Needed to preserve attribution to a different molecule without concealing favorable results. - Application exceptions: Do not calculate a new between-group effect from the two changes from baseline. - Remaining uncertainty: The complete original results tables and a single-active-ingredient B5 estimate are unverified in this review. - Referenced methods: M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses is this project's own design; M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for tests are this project's own design; M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are this project's own design; M04 §4.6.1–4.6.2, M15 §15.3.1; own application - Related sources: S101, S102 ### N18 · Are P=0.006 and P=0.010 the same comparison? Verification status: Partly verified Reading scope: The complete, exactly retained archived summary was actually read; the linked original material was not read in this review - Current findings: The between-group concentration comparison P=0.006 and the percentage-change comparison P=0.010 were preserved as distinct reported values from Evans's pantethine study. - Why unverified: The direct B5 P value is empty, and the detailed analyses for the two tests were not newly verified. - Reason for missing information: The direct B5 P value is empty, and the detailed analyses for the two tests were not newly verified. - Required materials and conditions: Concentration comparison, percentage-change comparison, actual analysis, and time points - Materials to obtain first: Concentration comparison, percentage-change comparison, actual analysis, and time points - Further research: Compare the concentration/percentage results tables and the analysis plan to verify the definition and denominator of each test. - Conditions for verification: Preserve the P values for the comparisons distinguished in the original text, their attribution, and the unverified aspects. - Why this condition is needed: Needed to avoid merging distinct reported tests into one. - Application exceptions: Do not convert a P value into an effect size or CI. - Remaining uncertainty: The direct B5 P value is empty, and the detailed analyses for the two tests were not newly verified. - Referenced methods: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are this project's own design; M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses is this project's own design; M08 §8.2.2, M15 §15.3.1; own application; M15 §15.3.1–15.3.3; own application - Related sources: S101 ### N19 · What do 32 allocated and 24 completed mean? Verification status: Partly verified Reading scope: The complete, exactly retained archived summary was actually read; the linked original material was not read in this review - Current findings: Evans was recorded as having 32 randomized and 24 completed. This information belongs to the pantethine trial and is not used as a direct B5 denominator. - Why unverified: Arm-specific LDL-C analysis denominators and the reasons for and handling of dropouts are unverified in the preserved text. - Reason for missing information: Arm-specific LDL-C analysis denominators and the reasons for and handling of dropouts are unverified in the preserved text. - Required materials and conditions: Evans allocation, completion, analyses by arm/endpoint, and reasons for dropout - Materials to obtain first: Evans allocation, completion, analyses by arm/endpoint, and reasons for dropout - Further research: Link Evans's participant flow with the outcome-specific analysis tables to review the denominators. - Conditions for verification: Preserve the related trial's original denominators and explain the unverified aspects of the direct/arm-specific analyses. - Why this condition is needed: Needed to avoid treating the overall allocation/completion counts as the same analysis denominator. - Application exceptions: Do not calculate new arm-specific dropout counts or rates from the difference. - Remaining uncertainty: Arm-specific LDL-C analysis denominators and the reasons for and handling of dropouts are unverified in the preserved text. - Referenced methods: M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; adaptations by study design are this project's own design; M08 §8.2.2, M15 §15.3.1; own application - Related sources: S101, S102 ### N20 · Are PMC and PubMed independent replication trials? Verification status: Partly verified Reading scope: The complete, exactly retained archived summary was actually read; the linked original material was not read in this review - Current findings: S101 PMC and S102 PubMed have the same DOI10.2147/VHRM.S57116 and PMID24600231 and refer to the Evans2014 trial. They were not counted as two independent replications. - Why unverified: Participant links with the other pantethine references were not verified in these materials. - Reason for missing information: Participant links with the other pantethine references were not verified in these materials. - Required materials and conditions: S101/S102 DOI, PMID, trial, and outcome linkage - Materials to obtain first: S101/S102 DOI, PMID, trial, and outcome linkage - Further research: Track registration, recruitment, participant, and trial identifiers across reports to check for overlap. - Conditions for verification: Distinguish verified links between reports of the same study from unresolved families. - Why this condition is needed: Needed to avoid counting reports as unique trials. - Application exceptions: Do not automatically establish that other references concern the same cohort or independent trials. - Remaining uncertainty: Participant links with the other pantethine references were not verified in these materials. - Referenced methods: Distinction between studies and reports in M04 §4.6.1–4.6.2; cohort/outcome linkage is an own application; M04 §4.6.1–4.6.2, M15 §15.3.1; own application - Related sources: S101, S102, L366-1, L366-2, L366-3 ### N21 · Were Evans's funding and independent replication verified? Verification status: Partly verified Reading scope: The complete, exactly retained archived summary was actually read; the linked original material was not read in this review - Current findings: The Evans pantethine trial was recorded as funded by Daiichi Fine Chemical Co Ltd. - Why unverified: This information belongs to pantethine and does not establish independent funding for direct B5 evidence or all conflicts of interest. - Reason for missing information: This information belongs to pantethine and does not establish independent funding for direct B5 evidence or all conflicts of interest. - Required materials and conditions: Reported funding, product/author relationships, institutions, and family linkage - Materials to obtain first: Reported funding, product/author relationships, institutions, and family linkage - Further research: Separately compare paper disclosures, product provision, author/institutional relationships, and study families. - Conditions for verification: Explain the verified funding and the scope of unverified disclosures/independence. - Why this condition is needed: Needed to avoid turning original funding reports into independent funding or absence of bias. - Application exceptions: Do not automatically exclude results because funding was provided. - Remaining uncertainty: This information belongs to pantethine and does not establish independent funding for direct B5 evidence or all conflicts of interest. - Referenced methods: Chamgap's own conditions for independence and attribution. The official methods sections used in this pilot do not guarantee all of these detailed items; distinction between studies and reports in M04 §4.6.1–4.6.2; cohort/outcome linkage is an own application - Related sources: S101, S102 ### N22 · Do mouse/adipocyte results answer the question about human LDL-C? Verification status: Partly verified Reading scope: The complete, exactly retained archived summary was actually read; the linked original material was not read in this review - Current findings: Zhao is a mechanistic study of adult male mice and primary adipocytes. It was not repurposed as a controlled human LDL-C trial of a single active ingredient. - Why unverified: The material read in this review is a preserved abstract/structured summary, and the full text of the original nonhuman results was not read. - Reason for missing information: The material read in this review is a preserved abstract/structured summary, and the full text of the original nonhuman results was not read. - Required materials and conditions: Species, sex, experimental system, measured endpoints, and whether a human comparison exists - Materials to obtain first: Species, sex, experimental system, measured endpoints, and whether a human comparison exists - Further research: Compare, for each material, the differences between the experimental endpoints and the human intervention, population, and LDL-C estimand. - Conditions for verification: Explain the difference between the actual nonhuman subjects and the direct human question. - Why this condition is needed: Needed to avoid transferring mechanistic observations to a human lipid effect of a single active ingredient. - Application exceptions: Preserve nonhuman studies within their scope without deleting them. - Remaining uncertainty: The material read in this review is a preserved abstract/structured summary, and the full text of the original nonhuman results was not read. - Referenced methods: M03 §3.2.1; detailed population conditions are this project's own design; M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are this project's own design; M03 §3.2.4; own boundary on extensions - Related sources: S103, S104 ### N23 · Are S103 and S104 the same study? Verification status: Unverified Reading scope: The complete, exactly retained archived summary was actually read; the linked original material was not read in this review - Current findings: S104 is a search-title/author/DOI lead, with no results extracted. It remains a possible related preprint of S103, and the exact relationship is unverified. - Why unverified: S104 was not counted as a new independent human trial or a verified nonhuman replication. - Reason for missing information: S104 was not counted as a new independent human trial or a verified nonhuman replication. - Required materials and conditions: Relationships among the preprint/paper, authors, experiments, and versions - Materials to obtain first: Relationships among the preprint/paper, authors, experiments, and versions - Further research: Check correspondence among versions, authors, experiments, and data, and record whether they belong to the same or different families. - Conditions for verification: Distinguish the preserved possible relationship, verified identifiers, and remaining gaps. - Why this condition is needed: Needed to avoid summing a possibly related preprint as an independent replication. - Application exceptions: Do not establish that studies are identical solely from similar titles. - Remaining uncertainty: S104 was not counted as a new independent human trial or a verified nonhuman replication. - Referenced methods: Distinction between studies and reports in M04 §4.6.1–4.6.2; cohort/outcome linkage is an own application; data collection/selection principles in M04 §4.5–4.6; separation of access and reading and the hyperlink contract are this project's own design; M04 §4.6.1–4.6.2, M15 §15.3.1; own application - Related sources: S103, S104 ### N24 · Is the NCT03444155 protocol a single-active-ingredient B5 result? Verification status: Partly verified Reading scope: The complete, exactly retained archived summary was actually read; the linked original material was not read in this review - Current findings: S105 is a natural versus synthetic B-complex protocol, v1.2/2017-04-13. The actual number randomized and single-active-ingredient LDL-C results are unverified. - Why unverified: The multicomponent protocol and registration were not counted as eligible single-active-ingredient trials. - Reason for missing information: The multicomponent protocol and registration were not counted as eligible single-active-ingredient trials. - Required materials and conditions: Protocol version, combination composition, comparator, administration plan, and actual results - Materials to obtain first: Protocol version, combination composition, comparator, administration plan, and actual results - Further research: Compare the planned composition, results/registration, and analysis plan to examine actual conduct and the contribution of the single ingredient. - Conditions for verification: Explain the attribution of the actual combination protocol and the unverified single-active-ingredient results. - Why this condition is needed: Needed to distinguish plans from results and contributions within a combination. - Application exceptions: A record of protocol access does not verify actual allocation or results. - Remaining uncertainty: The multicomponent protocol and registration were not counted as eligible single-active-ingredient trials. - Referenced methods: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for tests are this project's own design; M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are this project's own design; M03 §3.2.3, M08 §8.2.2–8.2.3; own application; M08 Table 8.2.a, M04 §4.6.3; own application - Related sources: S105, S106 ### N25 · Were the planned endpoint and reporting for the selected LDL-C outcome compared? Verification status: Unverified Reading scope: The complete, exactly retained archived summary was actually read; the linked original material was not read in this review - Current findings: Comparison of plans and reports for single-active-ingredient B5 LDL-C outcomes is unverified. S106 is a historical record that only a landing shell was returned; it does not mean that current recruitment/results or the complete outcome hierarchy were read. - Why unverified: Do not assess selective reporting for the direct single-active-ingredient question from partial reading of the combination S105 protocol. - Reason for missing information: Do not assess selective reporting for the direct single-active-ingredient question from partial reading of the combination S105 protocol. - Required materials and conditions: Directly eligible registration, protocol, SAP, and actual reporting/changes - Materials to obtain first: Directly eligible registration, protocol, SAP, and actual reporting/changes - Further research: Review the direct trial by linking registration, plans, reporting time points/analyses, and reasons for changes. - Conditions for verification: Indicate the actual scope of plan/report comparison for the direct comparison and the aspects not compared. - Why this condition is needed: Needed to identify the material required to check whether only favorable analyses were selected. - Application exceptions: Do not turn failure to acquire material into confirmation of nonregistration or selective reporting. - Remaining uncertainty: Do not assess selective reporting for the direct single-active-ingredient question from partial reading of the combination S105 protocol. - Referenced methods: Data collection/selection principles in M04 §4.5–4.6; separation of access and reading and the hyperlink contract are this project's own design; M04 §4.5, §4.6.3; limitations of the current material conversion follow the user's scope and this project's own design; M08 Table 8.2.a, M04 §4.6.3; own application - Related sources: S105, S106 ### N26 · Are the three references from the previous 366 direct B5 replications? Verification status: Partly verified Reading scope: The complete, exactly retained archived summary was actually read; the linked original material was not read in this review - Current findings: L366-1 Gaddi1984 and L366-3 Rumberger2011 are pantethine trial references, and L366-2 McRae2005 is a pantethine review. What was read in the current review is the inherited_local_citation preserved in 3100. - Why unverified: The earlier original files, external paper results, and cohort links with Evans were not read/are unverified in this review. - Reason for missing information: The earlier original files, external paper results, and cohort links with Evans were not read/are unverified in this review. - Required materials and conditions: Gaddi/Rumberger original trials, McRae review, molecules, and included study families - Materials to obtain first: Gaddi/Rumberger original trials, McRae review, molecules, and included study families - Further research: Compare the identities of the original trials, review inclusion tables, and related reports to check overlap and population differences. - Conditions for verification: Distinguish each material type, molecule, and unverified results/families. - Why this condition is needed: Needed to avoid summing earlier references, reviews, and trials as independent single-active-ingredient B5 replications. - Application exceptions: Do not carry over the previous C and 52 points to the new question. - Remaining uncertainty: The earlier original files, external paper results, and cohort links with Evans were not read/are unverified in this review. - Referenced methods: Distinction between studies and reports in M04 §4.6.1–4.6.2; cohort/outcome linkage is an own application; data collection/selection principles in M04 §4.5–4.6; separation of access and reading and the hyperlink contract are this project's own design; M04 §4.6.1–4.6.2, M15 §15.3.1; own application - Related sources: L366-1, L366-2, L366-3 ### N27 · Are skin 028 and acne 3099 LDL-C results? Verification status: Partly verified Reading scope: The complete, exactly retained archived summary was actually read; the linked original material was not read in this review - Current findings: L028 is a historical composite skin/hair record, and L3099 is a reference to the inflammatory acne question. They were not combined as direct results for the LDL-C question. - Why unverified: The referenced legacy files were not read in this review. The L3099 bibliographic URL is empty; do not invent successful original-text reading or a server URL from that time. - Reason for missing information: The referenced legacy files were not read in this review. The L3099 bibliographic URL is empty; do not invent successful original-text reading or a server URL from that time. - Required materials and conditions: Identity, endpoints, and linkage of the earlier composite skin/hair and acne questions - Materials to obtain first: Identity, endpoints, and linkage of the earlier composite skin/hair and acne questions - Further research: Compare differences in the identities, endpoints, and composition of the related original texts to the extent needed. - Conditions for verification: Preserve the differences between the original related questions and the selected LDL-C endpoint, and the reading gaps. - Why this condition is needed: Needed to avoid merging different outcomes for the same ingredient into this efficacy question. - Application exceptions: Reading the reference records in 3100 differs from directly reading the earlier original files. - Remaining uncertainty: The referenced legacy files were not read in this review. The L3099 bibliographic URL is empty; do not invent successful original-text reading or a server URL from that time. - Referenced methods: Question-clarification principles in M03 §3.1, §3.2.1–3.2.4; detailed separation rules are this project's own design; data collection/selection principles in M04 §4.5–4.6; separation of access and reading and the hyperlink contract are this project's own design; M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are this project's own design - Related sources: L028, L3099 ### N28 · What is the scope of the S107/S108/S109 materials? Verification status: Partly verified Reading scope: The complete, exactly retained archived summary was actually read; the linked original material was not read in this review - Current findings: S107 is a fortified margarine+B6 title and J-STAGE domain lead. S108 is a mixed-product/LDL oxidative-stability lead with an access failure at that time; S109 is a 2026 guideline domain lead, from which no B5 recommendation was extracted. - Why unverified: The existence of a lead does not verify individual results or current guideline content. - Reason for missing information: The existence of a lead does not verify individual results or current guideline content. - Required materials and conditions: Article identifiers, product composition, concentration/oxidative stability, and guideline full texts - Materials to obtain first: Article identifiers, product composition, concentration/oxidative stability, and guideline full texts - Further research: Verify article identity, product/endpoints, and original text to review eligibility for the direct question and the level of results. - Conditions for verification: Explain each lead's material type, different question, and unverified results. - Why this condition is needed: Needed to avoid turning search titles, access failures, and domain addresses into direct clinical results. - Application exceptions: Do not count inaccessible materials as negative trials. - Remaining uncertainty: The existence of a lead does not verify individual results or current guideline content. - Referenced methods: Data collection/selection principles in M04 §4.5–4.6; separation of access and reading and the hyperlink contract are this project's own design; M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are this project's own design; M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses is this project's own design; M04 §4.5, §4.6.3; limitations of the current material conversion follow the user's scope and this project's own design - Related sources: S107, S108, S109 ### N29 · Does an unverified direct result mean an effect of 0 or worldwide absence? Verification status: Met Reading scope: The complete, exactly retained archived summary was actually read; the linked original material was not read in this review - Current findings: Positive pantethine results and nonhuman/combination/lead materials were preserved. Unverified directly eligible single-active-ingredient B5 results were not turned into repeated refutation, an effect of 0, or worldwide absence. - Why unverified: The original no_human_study=true/human_study_exists=false applies to the fixed directly eligible question scope, and related_human_studies_exist=true is also preserved. - Reason for missing information: The original no_human_study=true/human_study_exists=false applies to the fixed directly eligible question scope, and related_human_studies_exist=true is also preserved. - Required materials and conditions: Verified direct/adjacent and positive/other results, and search scope/failures - Materials to obtain first: Verified direct/adjacent and positive/other results, and search scope/failures - Further research: In an authorized update, recompare search records, missing materials, and the reasons for each eligibility decision. - Conditions for verification: Explain attribution of all verified results and the limited scope of unverified direct evidence. - Why this condition is needed: Needed to avoid extending the finding to no effect, refutation, or absence of all studies worldwide. - Application exceptions: Do not turn access failures and incomplete searching into negative studies or 0 studies. - Remaining uncertainty: The original no_human_study=true/human_study_exists=false applies to the fixed directly eligible question scope, and related_human_studies_exist=true is also preserved. - Referenced methods: M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses is this project's own design; M04 §4.5, §4.6.3; limitations of the current material conversion follow the user's scope and this project's own design; M04 §4.6.1–4.6.2, M15 §15.3.1; own application - Related sources: S101, S103, S105, S107, S108 ### N30 · Were current summaries distinguished from historical full-text access? Verification status: Met Reading scope: The complete, exactly retained archived summary was actually read; the linked original material was not read in this review - Current findings: This review read the complete preserved archived summary of 3100 and the exact bibliographic/linkage summaries. The historical full_text for S101/S105 and the S06 inherited extraction, abstract/index/shell/access_failed/local_original are preserved separately, and the linked original materials were not read in this review. - Why unverified: The original historical full-text bytes, current file SHA, and actual access dates at that time are unverified. The original 2026-09-15 review date was not copied into individual material access dates. - Reason for missing information: The original historical full-text bytes, current file SHA, and actual access dates at that time are unverified. The original 2026-09-15 review date was not copied into individual material access dates. - Required materials and conditions: Publication, attempted/successful access, acquisition, reading, and actual dates and locations for each material - Materials to obtain first: Publication, attempted/successful access, acquisition, reading, and actual dates and locations for each material - Further research: Record the original identity, access/acquisition, actual locations read, and dates separately for each material. - Conditions for verification: Link the preserved locations actually read in the current review with each referenced material's unread status/historical record. - Why this condition is needed: Needed to avoid turning historical access_level into original-paper reading in this review. - Application exceptions: Do not label unattempted access as failed access or infer access dates from the overall review date. - Remaining uncertainty: The original historical full-text bytes, current file SHA, and actual access dates at that time are unverified. The original 2026-09-15 review date was not copied into individual material access dates. - Referenced methods: Data collection/selection principles in M04 §4.5–4.6; separation of access and reading and the hyperlink contract are this project's own design; M04 §4.5, §4.6.3; limitations of the current material conversion follow the user's scope and this project's own design - Related sources: S06, S101, S102, S103, S104, S105, S106, L366-1, L366-2, L366-3, L028, L3099, S107, S108, S109 ### N31 · Are the original grade, score, and axes new condition statuses? Verification status: Met Reading scope: The complete, exactly retained archived summary was actually read; the linked original material was not read in this review - Current findings: The original ?, empty score, B/S, empty values for the last 5 axes, unscored strengths, empty numerical/denominator fields in primary_effect, and the direct-eligibility gate/related human data were preserved. Pantethine C/52 and the skin composite C were not inherited. - Why unverified: No new efficacy grade, score, probability, or clinical calculation was produced. - Reason for missing information: No new efficacy grade, score, probability, or clinical calculation was produced. - Required materials and conditions: Original ?, empty values, B/S, unscored subsequent axes/strength, and gate/original calculation - Materials to obtain first: Original ?, empty values, B/S, unscored subsequent axes/strength, and gate/original calculation - Further research: In a separately authorized update, record the original calculation inputs/rules and reasons for changes, while preserving the original and its versions. - Conditions for verification: Preserve the original judgment values as quotations and distinguish them from conditions being met in the new table. - Why this condition is needed: Needed to avoid elevating an earlier score or an absence gate into a new judgment. - Application exceptions: The conditional record of the original C cap is also not an application or a new calculation in this review. - Remaining uncertainty: No new efficacy grade, score, probability, or clinical calculation was produced. - Referenced methods: Question-clarification principles in M03 §3.1, §3.2.1–3.2.4; detailed separation rules are this project's own design; M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses is this project's own design; M04 §4.5, §4.6.3; limitations of the current material conversion follow the user's scope and this project's own design - Related sources: ### N32 · Does an LDL-C difference answer questions about cardiovascular events or medication replacement? Verification status: Not applicable Reading scope: The complete, exactly retained archived summary was actually read; the linked original material was not read in this review - Current findings: This table concerns LDL-C concentration. Cardiovascular-event reduction and replacement of lipid medications were not imposed as additional requirements for the original question; they remain extensions requiring separate direct evidence. - Why unverified: This nonapplicability does not substitute for unverified direct LDL-C data. - Reason for missing information: This nonapplicability does not substitute for unverified direct LDL-C data. - Required materials and conditions: Boundary between the selected laboratory result and questions about events/treatment replacement - Materials to obtain first: Boundary between the selected laboratory result and questions about events/treatment replacement - Further research: Review direct clinical comparisons for a separate question that makes a claim about events or treatment replacement. - Conditions for verification: Distinguish the original question from a separate extension to clinical events. - Why this condition is needed: Needed to prevent automatic extension from a surrogate marker to prevention of clinical events. - Application exceptions: An event trial is not imposed as an additional requirement for the LDL-C concentration question itself. - Remaining uncertainty: This nonapplicability does not substitute for unverified direct LDL-C data. - Referenced methods: M03 §3.2.4; extension boundary specified by the author - Related sources: S101, S103, S105 ### N33 · Does the evidence answer questions about optimal dose, persistence after discontinuation, and all subgroups? Verification status: Not applicable Reading scope: The complete, exactly retained archived summary was actually read; the linked original material was not read in this review - Current findings: The current concentration comparison alone does not verify optimal dose, persistence after discontinuation, or effects in all subgroups, and these extensions were not imposed as additional requirements for the original question. - Why unverified: Gaps in directly eligible dose, duration, and population remain unchanged in their corresponding rows. - Reason for missing information: Gaps in directly eligible dose, duration, and population remain unchanged in their corresponding rows. - Required materials and conditions: Direct dose comparisons, discontinuation/long-term follow-up, and prespecified subgroups/interactions - Materials to obtain first: Direct dose comparisons, discontinuation/long-term follow-up, and prespecified subgroups/interactions - Further research: Link comparisons and outcomes appropriate to separate dose, follow-up, and effect-modification questions to the planned/actual analyses. - Conditions for verification: Separately distinguish extensions to dose/persistence and populations that are absent from direct comparisons. - Why this condition is needed: Needed to prevent extension of the narrow concentration question to optimal dose, persistence, or efficacy in all populations. - Application exceptions: Extension studies are not imposed as requirements for the current question as a whole. - Remaining uncertainty: Gaps in directly eligible dose, duration, and population remain unchanged in their corresponding rows. - Referenced methods: M03 §3.2.1–3.2.4; details on dose, persistence, and effect modification use the author's own design - Related sources: S101 ### N34 · Do high-dose harms and nutritional reference values establish a lipid-treatment dose? Verification status: Partly verified Reading scope: The complete, exactly retained archived summary was actually read; the linked original material was not read in this review - Current findings: The original Caution label and high-dose diarrhea/gastrointestinal discomfort were preserved. NIH's 10 g/day example and the adult adequate intake of 5 mg/day are not lipid-treatment doses or toxicity thresholds. The absence of an established upper limit does not mean unlimited safety. - Why unverified: Arm-specific events/discontinuations and denominators/durations in a direct LDL-C monotherapy trial are unverified, and pantethine bleeding/anticoagulation cautions were not copied to B5. - Reason for missing information: Arm-specific events/discontinuations and denominators/durations in a direct LDL-C monotherapy trial are unverified, and pantethine bleeding/anticoagulation cautions were not copied to B5. - Required materials and conditions: Harms involving the same ingredient, exposure, denominator/duration, collection, and nutritional reference values - Materials to obtain first: Harms involving the same ingredient, exposure, denominator/duration, collection, and nutritional reference values - Further research: Separately verify harm collection matched to the exposure, arm-specific events/discontinuations, and denominator/duration data. - Conditions for verification: Distinguish the original harm/nutrition descriptions from gaps in safety evidence from direct comparisons. - Why this condition is needed: Needed to prevent general descriptions of harms from being converted into incidence rates, treatment doses, or confirmation of overall safety. - Application exceptions: The 10 g/day example is not a toxicity threshold/recommendation, and 5 mg/day is the adult adequate intake. - Remaining uncertainty: Arm-specific events/discontinuations and denominators/durations in a direct LDL-C monotherapy trial are unverified, and pantethine bleeding/anticoagulation cautions were not copied to B5. - Referenced methods: M19 §19.1.2–19.2.4; the author's own application; M19 §19.1.2–19.2.4; detailed distinctions use the author's own design; Chamgap's own interpretive boundary. The principles of M19 are referenced; this is not an application of a formal causality tool - Related sources: S06 ### N35 · Has safety been verified for long-term high-dose use, concomitant use, and vulnerable populations? Verification status: Unverified Reading scope: The complete, exactly retained archived summary was actually read; the linked original material was not read in this review - Current findings: Safety for long-term high-dose use for LDL-C, pregnancy/lactation, children, and liver/kidney disease is unverified. The interaction description was not used as proof of safety for all combinations. - Why unverified: Do not convert research or nutritional values into personal dosing instructions. - Reason for missing information: Do not convert research or nutritional values into personal dosing instructions. - Required materials and conditions: Long-term use for LDL-C, pregnancy/lactation, children, liver/kidney disease, and concomitant use - Materials to obtain first: Long-term use for LDL-C, pregnancy/lactation, children, liver/kidney disease, and concomitant use - Further research: Review studies of harms from long-term use, use in special populations, and concomitant use with matching exposure/baseline risk and appropriate collection methods. - Conditions for verification: Indicate the limits of direct safety evidence for the selected purpose and gaps in populations/durations. - Why this condition is needed: Needed to prevent limited general records from being extended to safety in all populations/combinations. - Application exceptions: No known important interactions does not mean that all interactions have been excluded. - Remaining uncertainty: Do not convert research or nutritional values into personal dosing instructions. - Referenced methods: Design considerations in M19 §19.2.2–19.2.4; detailed confounding records use the author's own design; M19 §19.1.2–19.2.4; the author's own application; Chamgap's own interpretive boundary. The principles of M19 are referenced; this is not an application of a formal causality tool - Related sources: S06 ### N36 · What can change, as of which date and within which scope? Verification status: Met Reading scope: The complete, exactly retained archived summary was actually read; the linked original material was not read in this review - Current findings: The evidence/original review date is 2026-09-15, and this conversion is not a new clinical search, external full-text reading, calculation, regrading, or deployment. If new monotherapy trials, salts/products, LDL-C tables/denominators/SAP, corrections/retractions, or classification/numerical errors are verified, preserve the same ID/URL and the prior original text/history. - Why unverified: The original document_quality B, grade_revalidated, and self-review are original reports. They are not independent clinical/academic certification of the current table. - Reason for missing information: The original document_quality B, grade_revalidated, and self-review are original reports. They are not independent clinical/academic certification of the current table. - Required materials and conditions: Original evidence/review dates, actual current review, search scope, and new data/corrections/retractions - Materials to obtain first: Original evidence/review dates, actual current review, search scope, and new data/corrections/retractions - Further research: In a separately authorized update, preserve the identity of new material, its full original text, and the before/after values, and review the linked conditions again. - Conditions for verification: Separate the original dates and review/access levels from activities not currently performed and the conditions for updates. - Why this condition is needed: Needed to avoid overstating this conversion as a current comprehensive search, publication, or independent clinical certification. - Application exceptions: first_published_at is an editorial reference date, not proof of actual server publication. - Remaining uncertainty: The original document_quality B, grade_revalidated, and self-review are original reports. They are not independent clinical/academic certification of the current table. - Referenced methods: M04 §4.5, §4.6.3; the limits of the current data conversion follow the user's scope and the author's own design; data collection/selection principles in M04 §4.5–4.6; the separation of access from reading and the hyperlink contract use the author's own design; M04 §4.6.3, M15 §15.3.1–15.3.3; status distinctions use the author's own design - Related sources: ## Evidence and sources ### S06 NIH Office of Dietary Supplements. Pantothenic Acid — Health Professional Fact Sheet [Source](https://ods.od.nih.gov/factsheets/PantothenicAcid-HealthProfessional/) Materials actually read: The corresponding Korean/English summaries and bibliographic records in the archived manuscript were read. The linked external original materials were not read in this review. Findings recorded in the summary: Description of nutritional reference values, high-dose GI effects, absence of an established upper limit, and interactions; not an LDL-C monotherapy trial Record level: This is content recorded in the archived manuscript. It is not the result of a fresh comparison against current external original material. Independent replication: 15 bibliographic records ≠ 15 unique trials. The same Evans full text/abstract, possible preprint, combination protocol/registry, previous pantethine/reviews, different questions, and search/official materials are distinguished; participant summations performed: 0 | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Preserved archived-summary bibliography, linked summary/historical access | Locally preserved | Acquired | Summary read | The corresponding bibliography and linked summary in the archived manuscript were read. This does not mean that the full text of the original clinical article, protocol, or official document itself was acquired or read. | | Official web document | Unverified (current original-material lookups 0) | Access not attempted | Not read | No attempt was made to access this external original material or read its original text in this review. The address recorded in the bibliography is a route to the source; cases with no address or only a domain landing page were also left unchanged. Historical access level in the bibliography: inherited_full_text_extraction. The actual historical access date for each material is unverified. The archived manuscript's review date of 2026-09-15 is not the access date of the original material. Historical location: Table 1; Dietary supplements; Health Risks from Excessive Pantothenic Acid; Interactions with Medications | ### S101 Evans et al. 2014. Pantethine, a derivative of vitamin B5, favorably alters total, LDL and non-HDL cholesterol in low to moderate cardiovascular risk subjects eligible for statin therapy: a triple-blinded placebo and diet-controlled investigation [Source](https://pmc.ncbi.nlm.nih.gov/articles/PMC3942300/) Materials actually read: The corresponding Korean/English summaries and bibliographic records in the archived manuscript were read. The linked external original materials were not read in this review. Findings recorded in the summary: Pantethine 16 weeks · 32 randomized/24 completed · within-arm -11%/+3% · P0.006/0.010; ineligible as direct B5 evidence Record level: This is content recorded in the archived manuscript. It is not the result of a fresh comparison against current external original material. Independent replication: 15 bibliographic records ≠ 15 unique trials. The same Evans full text/abstract, possible preprint, combination protocol/registry, previous pantethine/reviews, different questions, and search/official materials are distinguished; participant summations performed: 0 | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Preserved archived-summary bibliography, linked summary/historical access | Locally preserved | Acquired | Summary read | The corresponding bibliography and linked summary in the archived manuscript were read. This does not mean that the full text of the original clinical article, protocol, or official document itself was acquired or read. | | PMC full-text page | Unverified (current original-material lookups 0) | Access not attempted | Not read | No attempt was made to access this external original material or read its original text in this review. The address recorded in the bibliography is a route to the source; cases with no address or only a domain landing page were also left unchanged. Historical access level in the bibliography: full_text. The actual historical access date for each material is unverified. The archived manuscript's review date of 2026-09-15 is not the access date of the original material. Historical location: Abstract; Methods: study design, inclusion criteria and primary endpoint; Results and Figures 2–3; Acknowledgments; Disclosure | ### S102 PubMed record for Evans et al. 2014 [Source](https://pubmed.ncbi.nlm.nih.gov/24600231/) Materials actually read: The corresponding Korean/English summaries and bibliographic records in the archived manuscript were read. The linked external original materials were not read in this review. Findings recorded in the summary: The same trial as S101, with the same DOI/PMID; not a separate replication Record level: This is content recorded in the archived manuscript. It is not the result of a fresh comparison against current external original material. Independent replication: 15 bibliographic records ≠ 15 unique trials. The same Evans full text/abstract, possible preprint, combination protocol/registry, previous pantethine/reviews, different questions, and search/official materials are distinguished; participant summations performed: 0 | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Preserved archived-summary bibliography, linked summary/historical access | Locally preserved | Acquired | Summary read | The corresponding bibliography and linked summary in the archived manuscript were read. This does not mean that the full text of the original clinical article, protocol, or official document itself was acquired or read. | | PubMed bibliography/abstract | Unverified (current original-material lookups 0) | Access not attempted | Not read | No attempt was made to access this external original material or read its original text in this review. The address recorded in the bibliography is a route to the source; cases with no address or only a domain landing page were also left unchanged. Historical access level in the bibliography: abstract. The actual historical access date for each material is unverified. The archived manuscript's review date of 2026-09-15 is not the access date of the original material. Historical location: Bibliography and abstract | ### S103 Zhao et al. Pantothenic Acid Alleviates Fat Deposition and Inflammation by Suppressing the JNK/P38 MAPK Signaling Pathway [Source](https://pubmed.ncbi.nlm.nih.gov/38949913/) Materials actually read: The corresponding Korean/English summaries and bibliographic records in the archived manuscript were read. The linked external original materials were not read in this review. Findings recorded in the summary: Mechanism in adult male mice/primary adipocytes; not attributed to human LDL-C Record level: This is content recorded in the archived manuscript. It is not the result of a fresh comparison against current external original material. Independent replication: 15 bibliographic records ≠ 15 unique trials. The same Evans full text/abstract, possible preprint, combination protocol/registry, previous pantethine/reviews, different questions, and search/official materials are distinguished; participant summations performed: 0 | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Preserved archived-summary bibliography, linked summary/historical access | Locally preserved | Acquired | Summary read | The corresponding bibliography and linked summary in the archived manuscript were read. This does not mean that the full text of the original clinical article, protocol, or official document itself was acquired or read. | | PubMed bibliography/abstract | Unverified (current original-material lookups 0) | Access not attempted | Not read | No attempt was made to access this external original material or read its original text in this review. The address recorded in the bibliography is a route to the source; cases with no address or only a domain landing page were also left unchanged. Historical access level in the bibliography: abstract. The actual historical access date for each material is unverified. The archived manuscript's review date of 2026-09-15 is not the access date of the original material. Historical location: Abstract: adult male mice and primary adipocytes; journal/date/DOI | ### S104 Preprint lead: Pantothenic acid alleviates fat deposition by preventing activation of the JNK/P38 MAPK pathway [Source](https://doi.org/10.21203/rs.3.rs-3412435/v1) Materials actually read: The corresponding Korean/English summaries and bibliographic records in the archived manuscript were read. The linked external original materials were not read in this review. Findings recorded in the summary: Title/author/DOI leads only; results/exact version linkage unverified Record level: This is content recorded in the archived manuscript. It is not the result of a fresh comparison against current external original material. Independent replication: 15 bibliographic records ≠ 15 unique trials. The same Evans full text/abstract, possible preprint, combination protocol/registry, previous pantethine/reviews, different questions, and search/official materials are distinguished; participant summations performed: 0 | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Preserved archived-summary bibliography, linked summary/historical access | Locally preserved | Acquired | Summary read | The corresponding bibliography and linked summary in the archived manuscript were read. This does not mean that the full text of the original clinical article, protocol, or official document itself was acquired or read. | | Preprint DOI page | Unverified (current original-material lookups 0) | Access not attempted | Not read | No attempt was made to access this external original material or read its original text in this review. The address recorded in the bibliography is a route to the source; cases with no address or only a domain landing page were also left unchanged. Historical access level in the bibliography: metadata_search_index. The actual historical access date for each material is unverified. The archived manuscript's review date of 2026-09-15 is not the access date of the original material. Historical location: Search title/author/DOI discovery only; no preprint results extracted | ### S105 NCT03444155 protocol and statistical plan, version 1.2 dated 2017-04-13: natural versus synthetic vitamin B complex [Source](https://cdn.clinicaltrials.gov/large-docs/55/NCT03444155/Prot_SAP_000.pdf) Materials actually read: The corresponding Korean/English summaries and bibliographic records in the archived manuscript were read. The linked external original materials were not read in this review. Findings recorded in the summary: v1.2/2017-04-13 · composition/administration plan; monotherapy results/actual randomization unverified Record level: This is content recorded in the archived manuscript. It is not the result of a fresh comparison against current external original material. Independent replication: 15 bibliographic records ≠ 15 unique trials. The same Evans full text/abstract, possible preprint, combination protocol/registry, previous pantethine/reviews, different questions, and search/official materials are distinguished; participant summations performed: 0 | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Preserved archived-summary bibliography, linked summary/historical access | Locally preserved | Acquired | Summary read | The corresponding bibliography and linked summary in the archived manuscript were read. This does not mean that the full text of the original clinical article, protocol, or official document itself was acquired or read. | | Protocol/SAP PDF | Unverified (current original-material lookups 0) | Access not attempted | Not read | No attempt was made to access this external original material or read its original text in this review. The address recorded in the bibliography is a route to the source; cases with no address or only a domain landing page were also left unchanged. Historical access level in the bibliography: full_text. The actual historical access date for each material is unverified. The archived manuscript's review date of 2026-09-15 is not the access date of the original material. Historical location: Protocol v1.2, 2017-04-13; printed pp. 5–6: multivitamin formulations and dosing plan. PDF pages 4 and 5 also inspected as screenshots. | ### S106 ClinicalTrials.gov landing page for NCT03444155 [Source](https://clinicaltrials.gov/study/NCT03444155) Materials actually read: The corresponding Korean/English summaries and bibliographic records in the archived manuscript were read. The linked external original materials were not read in this review. Findings recorded in the summary: Only a shell at the time; current recruitment/results/complete outcomes unverified Record level: This is content recorded in the archived manuscript. It is not the result of a fresh comparison against current external original material. Independent replication: 15 bibliographic records ≠ 15 unique trials. The same Evans full text/abstract, possible preprint, combination protocol/registry, previous pantethine/reviews, different questions, and search/official materials are distinguished; participant summations performed: 0 | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Preserved archived-summary bibliography, linked summary/historical access | Locally preserved | Acquired | Summary read | The corresponding bibliography and linked summary in the archived manuscript were read. This does not mean that the full text of the original clinical article, protocol, or official document itself was acquired or read. | | ClinicalTrials.gov registry page | Unverified (current original-material lookups 0) | Access not attempted | Not read | No attempt was made to access this external original material or read its original text in this review. The address recorded in the bibliography is a route to the source; cases with no address or only a domain landing page were also left unchanged. Historical access level in the bibliography: metadata_shell. The actual historical access date for each material is unverified. The archived manuscript's review date of 2026-09-15 is not the access date of the original material. Historical location: Only the landing shell was returned. Current recruitment/results/complete outcome hierarchy not read. | ### L366-1 Gaddi A, Descovich GC, Noseda G, et al. Controlled evaluation of pantethine, a natural hypolipidemic compound, in patients with different forms of hyperlipidemia. Atherosclerosis. 1984;50(1):73-83. PMID: 6365107. DOI: 10.1016/0021-9150(84)90009-1. [Source](https://pubmed.ncbi.nlm.nih.gov/6365107/) Materials actually read: The corresponding Korean/English summaries and bibliographic records in the archived manuscript were read. The linked external original materials were not read in this review. Findings recorded in the summary: Currently preserved as a legacy366 inherited citation; results/family relationships unverified Record level: This is content recorded in the archived manuscript. It is not the result of a fresh comparison against current external original material. Independent replication: 15 bibliographic records ≠ 15 unique trials. The same Evans full text/abstract, possible preprint, combination protocol/registry, previous pantethine/reviews, different questions, and search/official materials are distinguished; participant summations performed: 0 | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Preserved archived-summary bibliography, linked summary/historical access | Locally preserved | Acquired | Summary read | The corresponding bibliography and linked summary in the archived manuscript were read. This does not mean that the full text of the original clinical article, protocol, or official document itself was acquired or read. | | PubMed bibliographic page | Unverified (current original-material lookups 0) | Access not attempted | Not read | No attempt was made to access this external original material or read its original text in this review. The address recorded in the bibliography is a route to the source; cases with no address or only a domain landing page were also left unchanged. Historical access level in the bibliography: inherited_local_citation. The actual historical access date for each material is unverified. The archived manuscript's review date of 2026-09-15 is not the access date of the original material. Historical location: reference/legacy_366.json /citations/0; corresponding evidence row | ### L366-2 McRae MP. Treatment of hyperlipoproteinemia with pantethine: a review and analysis of efficacy and tolerability. Nutr Res. 2005;25(4):319-333. DOI: 10.1016/j.nutres.2004.12.009. [Source](https://doi.org/10.1016/j.nutres.2004.12.009) Materials actually read: The corresponding Korean/English summaries and bibliographic records in the archived manuscript were read. The linked external original materials were not read in this review. Findings recorded in the summary: Review ≠ B5 monotherapy trial; included studies/overlap unverified in this review Record level: This is content recorded in the archived manuscript. It is not the result of a fresh comparison against current external original material. Independent replication: 15 bibliographic records ≠ 15 unique trials. The same Evans full text/abstract, possible preprint, combination protocol/registry, previous pantethine/reviews, different questions, and search/official materials are distinguished; participant summations performed: 0 | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Preserved archived-summary bibliography, linked summary/historical access | Locally preserved | Acquired | Summary read | The corresponding bibliography and linked summary in the archived manuscript were read. This does not mean that the full text of the original clinical article, protocol, or official document itself was acquired or read. | | Review DOI page | Unverified (current original-material lookups 0) | Access not attempted | Not read | No attempt was made to access this external original material or read its original text in this review. The address recorded in the bibliography is a route to the source; cases with no address or only a domain landing page were also left unchanged. Historical access level in the bibliography: inherited_local_citation. The actual historical access date for each material is unverified. The archived manuscript's review date of 2026-09-15 is not the access date of the original material. Historical location: reference/legacy_366.json /citations/1; corresponding evidence row | ### L366-3 Rumberger JA, Napolitano J, Azumano I, Kamiya T, Evans M. Pantethine, a derivative of vitamin B5 used as a nutritional supplement, favorably alters low-density lipoprotein cholesterol metabolism in low- to moderate-cardiovascular risk North American subjects: a triple-blinded placebo and diet-controlled investigation. Nutr Res. 2011;31(8):608-615. PMID: 21925346. DOI: 10.1016/j.nutres.2011.08.001. [Source](https://pubmed.ncbi.nlm.nih.gov/21925346/) Materials actually read: The corresponding Korean/English summaries and bibliographic records in the archived manuscript were read. The linked external original materials were not read in this review. Findings recorded in the summary: Currently preserved as a legacy366 inherited citation; relationship to the Evans cohort unverified Record level: This is content recorded in the archived manuscript. It is not the result of a fresh comparison against current external original material. Independent replication: 15 bibliographic records ≠ 15 unique trials. The same Evans full text/abstract, possible preprint, combination protocol/registry, previous pantethine/reviews, different questions, and search/official materials are distinguished; participant summations performed: 0 | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Preserved archived-summary bibliography, linked summary/historical access | Locally preserved | Acquired | Summary read | The corresponding bibliography and linked summary in the archived manuscript were read. This does not mean that the full text of the original clinical article, protocol, or official document itself was acquired or read. | | PubMed bibliographic page | Unverified (current original-material lookups 0) | Access not attempted | Not read | No attempt was made to access this external original material or read its original text in this review. The address recorded in the bibliography is a route to the source; cases with no address or only a domain landing page were also left unchanged. Historical access level in the bibliography: inherited_local_citation. The actual historical access date for each material is unverified. The archived manuscript's review date of 2026-09-15 is not the access date of the original material. Historical location: reference/legacy_366.json /citations/2; corresponding evidence row | ### L028 Legacy 028: pantothenic acid × skin/hair, historical composite [Source](https://chamgap.com/verdicts/skin-hair/pantothenic-skin/) Materials actually read: The corresponding Korean/English summaries and bibliographic records in the archived manuscript were read. The linked external original materials were not read in this review. Findings recorded in the summary: A different question from LDL-C; the referenced legacy file was not read in this review Record level: This is content recorded in the archived manuscript. It is not the result of a fresh comparison against current external original material. Independent replication: 15 bibliographic records ≠ 15 unique trials. The same Evans full text/abstract, possible preprint, combination protocol/registry, previous pantethine/reviews, different questions, and search/official materials are distinguished; participant summations performed: 0 | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Preserved archived-summary bibliography, linked summary/historical access | Locally preserved | Acquired | Summary read | The corresponding bibliography and linked summary in the archived manuscript were read. This does not mean that the full text of the original clinical article, protocol, or official document itself was acquired or read. | | Reference material from previous work | Unverified (current original-material lookups 0) | Access not attempted | Not read | No attempt was made to access this external original material or read its original text in this review. The address recorded in the bibliography is a route to the source; cases with no address or only a domain landing page were also left unchanged. Historical access level in the bibliography: local_original. The actual historical access date for each material is unverified. The archived manuscript's review date of 2026-09-15 is not the access date of the original material. Historical location: reference/legacy_028.json; inherited prior R01-021 extraction; no new skin/hair investigation | ### L3099 Completed R01-021: oral pantothenic acid monotherapy × inflammatory acne lesions Materials actually read: The corresponding Korean/English summaries and bibliographic records in the archived manuscript were read. The linked external original materials were not read in this review. Findings recorded in the summary: Inflammatory lesions ≠ LDL-C; empty URL in the preserved bibliography/server URL unverified at the time Record level: This is content recorded in the archived manuscript. It is not the result of a fresh comparison against current external original material. Independent replication: 15 bibliographic records ≠ 15 unique trials. The same Evans full text/abstract, possible preprint, combination protocol/registry, previous pantethine/reviews, different questions, and search/official materials are distinguished; participant summations performed: 0 | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Preserved archived-summary bibliography, linked summary/historical access | Locally preserved | Acquired | Summary read | The corresponding bibliography and linked summary in the archived manuscript were read. This does not mean that the full text of the original clinical article, protocol, or official document itself was acquired or read. | | Reference material from previous work | Unverified (current original-material lookups 0) | Access not attempted | Not read | No attempt was made to access this external original material or read its original text in this review. The address recorded in the bibliography is a route to the source; cases with no address or only a domain landing page were also left unchanged. Historical access level in the bibliography: local_original. The actual historical access date for each material is unverified. The archived manuscript's review date of 2026-09-15 is not the access date of the original material. Historical location: reference/reused_TASK0021.json; ID 3099 is supplied by the user, no server URL verified | ### S107 Discovery lead: Influence of Several Lipids on Human Serum Cholesterol (Part 9), enriched margarine with pantothenic acid and vitamin B6 [Source](https://www.jstage.jst.go.jp/) Materials actually read: The corresponding Korean/English summaries and bibliographic records in the archived manuscript were read. The linked external original materials were not read in this review. Findings recorded in the summary: J-STAGE domain address; article identifier, original text, and numerical values unverified Record level: This is content recorded in the archived manuscript. It is not the result of a fresh comparison against current external original material. Independent replication: 15 bibliographic records ≠ 15 unique trials. The same Evans full text/abstract, possible preprint, combination protocol/registry, previous pantethine/reviews, different questions, and search/official materials are distinguished; participant summations performed: 0 | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Preserved archived-summary bibliography, linked summary/historical access | Locally preserved | Acquired | Summary read | The corresponding bibliography and linked summary in the archived manuscript were read. This does not mean that the full text of the original clinical article, protocol, or official document itself was acquired or read. | | Academic-platform domain page | Unverified (current original-material lookups 0) | Access not attempted | Not read | No attempt was made to access this external original material or read its original text in this review. The address recorded in the bibliography is a route to the source; cases with no address or only a domain landing page were also left unchanged. Historical access level in the bibliography: metadata_search_index. The actual historical access date for each material is unverified. The archived manuscript's review date of 2026-09-15 is not the access date of the original material. Historical location: Search title only; retrieved URL is a domain landing page, not an article locator. Full article, study identifiers and numerical results not obtained. | ### S108 Discovery lead: Kim et al. mixed nutraceutical / LDL stability study, Nutrients 2013;5:5218 [Source](https://www.mdpi.com/2072-6643/5/12/5218) Materials actually read: The corresponding Korean/English summaries and bibliographic records in the archived manuscript were read. The linked external original materials were not read in this review. Findings recorded in the summary: Historical article access_failed; B5 monotherapy concentration estimate not accepted Record level: This is content recorded in the archived manuscript. It is not the result of a fresh comparison against current external original material. Independent replication: 15 bibliographic records ≠ 15 unique trials. The same Evans full text/abstract, possible preprint, combination protocol/registry, previous pantethine/reviews, different questions, and search/official materials are distinguished; participant summations performed: 0 | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Preserved archived-summary bibliography, linked summary/historical access | Locally preserved | Acquired | Summary read | The corresponding bibliography and linked summary in the archived manuscript were read. This does not mean that the full text of the original clinical article, protocol, or official document itself was acquired or read. | | Publisher article page | Unverified (current original-material lookups 0) | Access not attempted | Not read | No attempt was made to access this external original material or read its original text in this review. The address recorded in the bibliography is a route to the source; cases with no address or only a domain landing page were also left unchanged. Historical access level in the bibliography: access_failed. The actual historical access date for each material is unverified. The archived manuscript's review date of 2026-09-15 is not the access date of the original material. Historical location: Search lead indicates a multicomponent product and LDL oxidative stability; attempted article access failed. No isolated B5 LDL-C estimate accepted. | ### S109 Discovery lead: 2026 dyslipidemia guideline key messages [Source](https://professional.heart.org/) Materials actually read: The corresponding Korean/English summaries and bibliographic records in the archived manuscript were read. The linked external original materials were not read in this review. Findings recorded in the summary: Domain root only; full guideline not read; no B5 recommendation extracted Record level: This is content recorded in the archived manuscript. It is not the result of a fresh comparison against current external original material. Independent replication: 15 bibliographic records ≠ 15 unique trials. The same Evans full text/abstract, possible preprint, combination protocol/registry, previous pantethine/reviews, different questions, and search/official materials are distinguished; participant summations performed: 0 | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Preserved archived-summary bibliography, linked summary/historical access | Locally preserved | Acquired | Summary read | The corresponding bibliography and linked summary in the archived manuscript were read. This does not mean that the full text of the original clinical article, protocol, or official document itself was acquired or read. | | Professional-society domain page | Unverified (current original-material lookups 0) | Access not attempted | Not read | No attempt was made to access this external original material or read its original text in this review. The address recorded in the bibliography is a route to the source; cases with no address or only a domain landing page were also left unchanged. Historical access level in the bibliography: metadata_search_index. The actual historical access date for each material is unverified. The archived manuscript's review date of 2026-09-15 is not the access date of the original material. Historical location: Targeted search returned a domain-root key-messages result, not readable full guideline. No B5-specific efficacy conclusion or recommendation extracted. | ## Review criteria and methods These are Chamgap's own application conditions, informed by the relevant sections of official methodological guidance. They do not constitute official assessment-tool certification or a new efficacy score. - M03 [Cochrane Handbook 6.5 (2024), chapter updated 2023-08](https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-03) · §3.1, §3.2.1–3.2.3, MECIR C5/C7/C13 · Clearly record the question, eligibility conditions, and reasons for changes, and distinguish variations of the intervention. · Reuse of the preserved methodological principles/version from 1585 and the actual 5 HTML copies; not a new reading of full methodological texts or application of official tools - M04 [Cochrane Handbook 6.5.1 (2025), chapter updated 2025-03](https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-04) · §4.5, §4.6.1–4.6.3, MECIR C42 · Distinguish and link studies and reports, and do not omit a study merely because an outcome is unreported. · Reuse of the preserved methodological principles/version from 1585 and the actual 5 HTML copies; not a new reading of full methodological texts or application of official tools - 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, and review randomization, deviations, missingness, measurement, and selective reporting. · Reuse of the preserved methodological principles/version from 1585 and the actual 5 HTML copies; not a new reading of full methodological texts or application of official tools - M15 [Cochrane Handbook 6.5 (2024), chapter updated 2023-08](https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-15) · §15.2.4, §15.3.1–15.3.3 · Distinguish effect estimates, intervals, importance, and applicability. Sample size alone does not determine precision. · Reuse of the preserved methodological principles/version from 1585 and the actual 5 HTML copies; not a new reading of full methodological texts or application of official tools - 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 · A harm question may require designs, populations, and follow-up different from those for efficacy. Case reports do not establish incidence rates. · Reuse of the preserved methodological principles/version from 1585 and the actual 5 HTML copies; not a new reading of full methodological texts or application of official tools ## What the statuses mean - Partly verified: Some adjacent/bibliographic and historical information verified; gaps remain in direct monotherapy evidence, outcomes, denominators, plans, and access - Unverified: The selected direct outcome or necessary material could not be verified within the preserved scope; this does not mean 0 studies or no effect - Review incomplete: Original-material comparison/search was not performed within the permitted scope - Not reported: A scope-limited status meaning that the item was not stated in the specific material/section read - Inaccessible: Used only for material for which access was actually attempted and failed. Not assigned to clinical material in this review - Insufficient evidence meeting the conditions: Used only when evidence is insufficient to answer a condition after relevant studies within the defined scope have been reviewed. Not applied comprehensively in this review - Not applicable: Extensions to events, optimal dose, persistence, or all populations are not imposed as additional requirements for the selected concentration question; this does not substitute for unverified data - Conflicting information: When materials that are difficult to reconcile for the same question, time point, and analysis have been compared. Not assigned merely because a review reports different numerical values - Met: Verification of the stated preservation, boundaries/measures/attribution, and material linkages; not direct B5 LDL-C efficacy, full-text reading, or safety certification ## Change history 2026-11-02 · Public page/materials 1.0. A public view and data were prepared from the existing 36 items. No new clinical search, change in verification status, or scoring was performed.