Oral single-active-ingredient pantothenic acid (vitamin B5) supplementation × Reduction in LDL-C concentration in adults with elevated LDL-C

Required evidence, verification status and materials actually read
Item	AVerification status	BReading scope	CReview item	DCurrent findings	EWhy unverified	FRequired materials and conditions	GFurther research
1	Met	Full text not readStored summary read	N01 · Independent claimWhich ingredient, population, and LDL-C comparison?Required (selected B5 monotherapy and LDL-C comparison)	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. S101 S105	This verifies the identity of the question, not direct efficacy.	Adults with elevated LDL-C, oral B5 monotherapy, comparator with the same background treatment, between-group change in LDL-C	Compare differences in ingredient, population, endpoint, and comparison between the existing question and candidate results for each material.
2	Met	Full text not readStored summary read	N02 · Molecule and routeAre pantothenic acid and pantethine the same intervention?Required (selected B5 monotherapy and LDL-C comparison)	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. S101 S06 L028	Verifying the substance boundary is separate from verifying the specifications of an eligible product.	Exact molecule, salt, active ingredient, and route of administration	Compare product composition and chemical-form documents for each result to verify whether the active ingredient is the same.
3	Unverified	Full text not readStored summary read	N03 · Product specificationsAre the origin, salt, and formulation of an eligible single-active-ingredient product known?Required (selected B5 monotherapy and LDL-C comparison)	The origin, brand, salt, purity, batch, formulation, and release type of an eligible pantothenic-acid single-active-ingredient product are unverified. S101 S105	Specifications not supplied by the current material were not taken from related products.	Manufacturing origin, brand, exact salt, purity, batch, tablet/capsule, and release type	Verify formulation analysis, batch, and composition materials by linking them to actual comparative trial results.
4	Unverified	Full text not readStored summary read	N04 · Dose and frequencyWhat are the actual dose and total exposure for B5 monotherapy?Required (selected B5 monotherapy and LDL-C comparison)	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. S101 S06	No new calcium-salt mass conversion or personal dosage was created.	Single-active-ingredient dose, frequency, active amount, dietary/concurrent supplementation, and adherence	Collect administration, composition, adherence, and dietary-exposure records by arm to examine actual differences in intervention.
5	Unverified	Full text not readStored summary read	N05 · Duration and time pointsHave the directly relevant treatment duration and assessment time points been verified?Required (selected B5 monotherapy and LDL-C comparison)	Eligible monotherapy treatment duration and LDL-C assessment time points are unverified. 16 weeks is the duration of the Evans pantethine trial. S101 S105	Duration for a different molecule does not meet the selected comparison.	Single-active-ingredient administration duration, planned/actual LDL-C time points, and follow-up	Compare the plan, actual exposure, and time points in outcome tables to distinguish prespecified endpoints from follow-up.
6	Unverified	Full text not readStored summary read	N06 · Population selectionHow were adults with elevated LDL-C selected?Required (selected B5 monotherapy and LDL-C comparison)	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. S101	The population of a related trial is attributed only to that trial.	Diagnostic threshold, baseline LDL-C, age, inclusion/exclusion, and setting	Obtain recruitment and baseline tables and exclusion criteria, and compare them with the population in the selected question.
7	Unverified	Full text not readStored summary read	N07 · Baseline and concomitant treatmentCan lipid-lowering medications, diet, deficiency, and other supplementation be distinguished?Required (selected B5 monotherapy and LDL-C comparison)	Medication, deficiency, and dietary/concurrent-supplementation status in the directly eligible population are unverified. S101 S105	The description of a diet-controlled pantethine study is not a concomitant-treatment condition in the selected B5 trial.	Arm-specific lipid-lowering medications, diet, deficiency/nutritional status, and concurrent supplementation	Compare baseline nutrition, medications, diet, and records of arm-specific changes with analyses for each outcome.
8	Unverified	Full text not readStored summary read	N08 · Comparator and background treatmentWhat are the placebo or usual care and the actual shared treatment?Required (selected B5 monotherapy and LDL-C comparison)	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. S101 S105 S106	A comparison of two B-complex formulations is not a placebo comparison of B5 monotherapy.	Actual placebo composition, usual care, rescue treatment, and arm-specific changes	Link arm-specific prescriptions, comparator composition, rescue treatment/changes, and analysis plans to verify the scope of contribution.
9	Unverified	Full text not readStored summary read	N09 · Measurement methodWere directly measured LDL and formula-calculated LDL distinguished?Required (selected B5 monotherapy and LDL-C comparison)	There is no information to distinguish directly measured LDL from formula-calculated LDL, and measurement procedures in eligible monotherapy trials are unverified. S101 S108	Measurement information or results were not filled in through unit conversion or graph reconstruction.	LDL measurement method, specimen/blood collection, calculation formula, and arm-specific procedures	Compare measurement methods, calculation formulas, blood-collection conditions, and assessment procedures with each outcome table.
10	Met	Full text not readStored summary read	N10 · Endpoint and unitsAre differences in change, endpoint differences, and percentages the same value?Required (selected B5 monotherapy and LDL-C comparison)	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. S101	This verifies the distinction between measures; it does not mean that single-active-ingredient results were obtained.	LDL-C definition, units, baseline/change/endpoint values, and between-group/within-group distinctions	Link outcome definitions, analyses, units, and time points to the original tables and protocol, preserving each separately.
11	Unverified	Full text not readStored summary read	N11 · Effect of interestWhat intervention effect does an eligible analysis estimate?Required (selected B5 monotherapy and LDL-C comparison)	Baseline, change, and endpoint values and actual between-group analyses for B5 monotherapy are unverified. S101	Do not fill a direct B5 estimate with related pantethine analyses.	Between-group/within-group, change/endpoint, adjustment, ITT/PP, and analysis population	Compare the analysis plan with actual outcome tables to verify the effect of interest, adjustment, and denominators.
12	Unverified	Full text not readStored summary read	N12 · Effect and intervalAre the directly relevant LDL-C effect, CI, and P value known?Required (selected B5 monotherapy and LDL-C comparison)	Within primary_effect, the records for mean_difference, confidence_interval, p_value, and analysis sample size are empty/not_verified. S101 S105	This does not confirm an effect of 0, equivalence, or the absence of a directly relevant effect.	Eligible between-group effect, uncertainty interval, P value, and units	Review estimates, intervals, variance, and denominators in eligible outcome tables by attributing them to the actual analyses.
13	Unverified	Full text not readStored summary read	N13 · Directly relevant denominatorsHow many participants were allocated, measured, analyzed, and completed, respectively?Required (selected B5 monotherapy and LDL-C comparison)	Arm-specific LDL-C analysis denominators and allocated/completed counts in eligible B5 monotherapy trials are unverified. S101 S102	Denominators from related studies were not transferred, and no new missing counts or rates were calculated.	Arm-specific allocation/analysis/completion for the single-active-ingredient treatment, missing data, and outcome-specific denominators	Compare participant flow, reasons for missing data, and outcome-specific analysis tables to verify denominators.
14	Unverified	Full text not readStored summary read	N14 · Allocation and assessmentAre the design, concealment, and blinding of the monotherapy comparison known?Required (selected B5 monotherapy and LDL-C comparison)	The related Evans pantethine study is a triple-blind trial, but the directly relevant design, allocation, concealment, and blinding for B5 monotherapy are unverified. S101 S102	Do not label this as formal execution of RoB 2 or absence of bias.	Actual design, allocation/concealment, baseline balance, and assessment procedures	Obtain monotherapy methods, registration, and baseline/assessment materials and review them at the outcome level.
15	Unverified	Full text not readStored summary read	N15 · Adherence and discontinuationAre adherence, rescue treatment, analysis populations, and missing-data handling known?Required (selected B5 monotherapy and LDL-C comparison)	Adherence to the single-active-ingredient product, withdrawals by arm, analysis populations, and handling of missing data are unverified. S101	Pantethine allocation/completion counts alone do not reveal how the selected results were handled.	Actual intake, discontinuation, arm-specific changes, ITT/PP, and missing-data handling	Compare the analysis plan, administration records, and participant flow against the results tables to examine their impact.
16	Unverified	Full text not readStored summary read	N16 · Precision and importanceWhat magnitudes of difference does the reported interval allow?Required (selected B5 monotherapy and LDL-C comparison)	The direct LDL-C CI, variance, and important-difference criterion are unverified, and the original precision axis is an unscored empty value. S101	Do not use an unverified interval to exclude an important effect or create a new grade.	Direct effect/CI, variance, and a justified important difference	Obtain the basis for importance appropriate to the endpoint/population and the actual reported interval separately, and compare them.
17	Partly verified	Full text not readStored summary read	N17 · Positive adjacent resultsWhat produced the LDL-C improvement in Evans?Required (selected B5 monotherapy and LDL-C comparison)	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. S101 S102	The complete original results tables and a single-active-ingredient B5 estimate are unverified in this review.	Actual ingredients, within-arm changes, time points, and original tables from the pantethine trial	Compare the original LDL-C tables against the product/analysis documents to verify the scope of the reported values.
18	Partly verified	Full text not readStored summary read	N18 · Different P testsAre P=0.006 and P=0.010 the same comparison?Required (selected B5 monotherapy and LDL-C comparison)	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. S101	The direct B5 P value is empty, and the detailed analyses for the two tests were not newly verified.	Concentration comparison, percentage-change comparison, actual analysis, and time points	Compare the concentration/percentage results tables and the analysis plan to verify the definition and denominator of each test.
19	Partly verified	Full text not readStored summary read	N19 · Adjacent-study denominatorsWhat do 32 allocated and 24 completed mean?Required (selected B5 monotherapy and LDL-C comparison)	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. S101 S102	Arm-specific LDL-C analysis denominators and the reasons for and handling of dropouts are unverified in the preserved text.	Evans allocation, completion, analyses by arm/endpoint, and reasons for dropout	Link Evans's participant flow with the outcome-specific analysis tables to review the denominators.
20	Partly verified	Full text not readStored summary read	N20 · Reports of the same trialAre PMC and PubMed independent replication trials?Required (selected B5 monotherapy and LDL-C comparison)	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. S101 S102 L366-1 L366-2 L366-3	Participant links with the other pantethine references were not verified in these materials.	S101/S102 DOI, PMID, trial, and outcome linkage	Track registration, recruitment, participant, and trial identifiers across reports to check for overlap.
21	Partly verified	Full text not readStored summary read	N21 · Funding and independenceWere Evans's funding and independent replication verified?Required (selected B5 monotherapy and LDL-C comparison)	The Evans pantethine trial was recorded as funded by Daiichi Fine Chemical Co Ltd. S101 S102	This information belongs to pantethine and does not establish independent funding for direct B5 evidence or all conflicts of interest.	Reported funding, product/author relationships, institutions, and family linkage	Separately compare paper disclosures, product provision, author/institutional relationships, and study families.
22	Partly verified	Full text not readStored summary read	N22 · Nonhuman mechanismsDo mouse/adipocyte results answer the question about human LDL-C?Required (selected B5 monotherapy and LDL-C comparison)	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. S103 S104	The material read in this review is a preserved abstract/structured summary, and the full text of the original nonhuman results was not read.	Species, sex, experimental system, measured endpoints, and whether a human comparison exists	Compare, for each material, the differences between the experimental endpoints and the human intervention, population, and LDL-C estimand.
23	Unverified	Full text not readStored summary read	N23 · Possible preprintAre S103 and S104 the same study?Required (selected B5 monotherapy and LDL-C comparison)	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. S103 S104	S104 was not counted as a new independent human trial or a verified nonhuman replication.	Relationships among the preprint/paper, authors, experiments, and versions	Check correspondence among versions, authors, experiments, and data, and record whether they belong to the same or different families.
24	Partly verified	Full text not readStored summary read	N24 · Combination-product protocolIs the NCT03444155 protocol a single-active-ingredient B5 result?Required (selected B5 monotherapy and LDL-C comparison)	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. S105 S106	The multicomponent protocol and registration were not counted as eligible single-active-ingredient trials.	Protocol version, combination composition, comparator, administration plan, and actual results	Compare the planned composition, results/registration, and analysis plan to examine actual conduct and the contribution of the single ingredient.
25	Unverified	Full text not readStored summary read	N25 · Registration and selective reportingWere the planned endpoint and reporting for the selected LDL-C outcome compared?Required (selected B5 monotherapy and LDL-C comparison)	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. S105 S106	Do not assess selective reporting for the direct single-active-ingredient question from partial reading of the combination S105 protocol.	Directly eligible registration, protocol, SAP, and actual reporting/changes	Review the direct trial by linking registration, plans, reporting time points/analyses, and reasons for changes.
26	Partly verified	Full text not readStored summary read	N26 · Earlier pantethine referencesAre the three references from the previous 366 direct B5 replications?Required (selected B5 monotherapy and LDL-C comparison)	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. L366-1 L366-2 L366-3	The earlier original files, external paper results, and cohort links with Evans were not read/are unverified in this review.	Gaddi/Rumberger original trials, McRae review, molecules, and included study families	Compare the identities of the original trials, review inclusion tables, and related reports to check overlap and population differences.
27	Partly verified	Full text not readStored summary read	N27 · Earlier different questionsAre skin 028 and acne 3099 LDL-C results?Required (selected B5 monotherapy and LDL-C comparison)	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. L028 L3099	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.	Identity, endpoints, and linkage of the earlier composite skin/hair and acne questions	Compare differences in the identities, endpoints, and composition of the related original texts to the extent needed.
28	Partly verified	Full text not readStored summary read	N28 · Mixed-product and search leadsWhat is the scope of the S107/S108/S109 materials?Required (selected B5 monotherapy and LDL-C comparison)	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. S107 S108 S109	The existence of a lead does not verify individual results or current guideline content.	Article identifiers, product composition, concentration/oxidative stability, and guideline full texts	Verify article identity, product/endpoints, and original text to review eligibility for the direct question and the level of results.
29	Met	Full text not readStored summary read	N29 · Scope of contrary findings and absenceDoes an unverified direct result mean an effect of 0 or worldwide absence?Required (selected B5 monotherapy and LDL-C comparison)	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. S101 S103 S105 S107 S108	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.	Verified direct/adjacent and positive/other results, and search scope/failures	In an authorized update, recompare search records, missing materials, and the reasons for each eligibility decision.
30	Met	Full text not readStored summary read	N30 · Materials and readingWere current summaries distinguished from historical full-text access?Required (selected B5 monotherapy and LDL-C comparison)	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. S06 S101 S102 S103 S104 S105 S106 L366-1 L366-2 L366-3 L028 L3099 S107 S108 S109	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.	Publication, attempted/successful access, acquisition, reading, and actual dates and locations for each material	Record the original identity, access/acquisition, actual locations read, and dates separately for each material.
31	Met	Full text not readStored summary read	N31 · Preservation of the original judgmentAre the original grade, score, and axes new condition statuses?Required (selected B5 monotherapy and LDL-C comparison)	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.	No new efficacy grade, score, probability, or clinical calculation was produced.	Original ?, empty values, B/S, unscored subsequent axes/strength, and gate/original calculation	In a separately authorized update, record the original calculation inputs/rules and reasons for changes, while preserving the original and its versions.
32	Not applicable	Full text not readStored summary read	N32 · Extension to clinical eventsDoes an LDL-C difference answer questions about cardiovascular events or medication replacement?Supplementary (boundary for extension to clinical events)	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. S101 S103 S105	This nonapplicability does not substitute for unverified direct LDL-C data.	Boundary between the selected laboratory result and questions about events/treatment replacement	Review direct clinical comparisons for a separate question that makes a claim about events or treatment replacement.
33	Not applicable	Full text not readStored summary read	N33 · Extensions to dose and persistenceDoes the evidence answer questions about optimal dose, persistence after discontinuation, and all subgroups?Supplementary (extensions to dose, persistence, and populations)	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. S101	Gaps in directly eligible dose, duration, and population remain unchanged in their corresponding rows.	Direct dose comparisons, discontinuation/long-term follow-up, and prespecified subgroups/interactions	Link comparisons and outcomes appropriate to separate dose, follow-up, and effect-modification questions to the planned/actual analyses.
34	Partly verified	Full text not readStored summary read	N34 · General harms and nutritionDo high-dose harms and nutritional reference values establish a lipid-treatment dose?Required (selected B5 monotherapy and LDL-C comparison)	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. S06	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.	Harms involving the same ingredient, exposure, denominator/duration, collection, and nutritional reference values	Separately verify harm collection matched to the exposure, arm-specific events/discontinuations, and denominator/duration data.
35	Unverified	Full text not readStored summary read	N35 · Long-term use and vulnerable populationsHas safety been verified for long-term high-dose use, concomitant use, and vulnerable populations?Supplementary (extension to long-term/concomitant-use safety)	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. S06	Do not convert research or nutritional values into personal dosing instructions.	Long-term use for LDL-C, pregnancy/lactation, children, liver/kidney disease, and concomitant use	Review studies of harms from long-term use, use in special populations, and concomitant use with matching exposure/baseline risk and appropriate collection methods.
36	Met	Full text not readStored summary read	N36 · Reference date and updatesWhat can change, as of which date and within which scope?Required (selected B5 monotherapy and LDL-C comparison)	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.	The original document_quality B, grade_revalidated, and self-review are original reports. They are not independent clinical/academic certification of the current table.	Original evidence/review dates, actual current review, search scope, and new data/corrections/retractions	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.

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36 itemsWhat the statuses mean

Assessment scope

Stored-material review date: 2026-10-05
Original evidence date: 2026-09-15
Scope actually checked: Archived Korean and English manuscripts and case-specific conditions and application records. Full papers, supplements, registrations, plans and original data were not read.
What the dates mean: This is the date the archived material was checked, not the date of the latest clinical literature search.
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.

Evidence and sources

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

S06 · NIH Office of Dietary Supplements. Pantothenic Acid — Health Professional Fact Sheet

Source

Material type: NIH nutrition and safety document
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 stored 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.
Study overlap and 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

Public availability, access and reading status by material
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

Material type: Evans2014 PMC original-article bibliography
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 stored 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.
Study overlap and 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

Public availability, access and reading status by material
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

Material type: Bibliography/abstract for the same Evans study in PubMed
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 stored 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.
Study overlap and 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

Public availability, access and reading status by material
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

Material type: Bibliography/abstract for the nonhuman Zhao paper
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 stored 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.
Study overlap and 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

Public availability, access and reading status by material
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

Material type: Search bibliography for a possibly related preprint
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 stored 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.
Study overlap and 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

Public availability, access and reading status by material
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

Material type: Bibliography for the B-complex protocol
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 stored 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.
Study overlap and 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

Public availability, access and reading status by material
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

Material type: Bibliography for the same NCT registry landing page
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 stored 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.
Study overlap and 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

Public availability, access and reading status by material
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

Material type: Gaddi1984 previous pantethine bibliography
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 stored 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.
Study overlap and 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

Public availability, access and reading status by material
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

Material type: McRae2005 previous pantethine-review bibliography
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 stored 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.
Study overlap and 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

Public availability, access and reading status by material
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

Material type: Rumberger2011 previous pantethine bibliography
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 stored 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.
Study overlap and 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

Public availability, access and reading status by material
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

Material type: Reference to a previous composite skin/hair record
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 stored 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.
Study overlap and 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

Public availability, access and reading status by material
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

Material type: Reference to the previous 3099 acne record
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 stored 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.
Study overlap and 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

Public availability, access and reading status by material
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

Material type: Fortified margarine+B6 search title
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 stored 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.
Study overlap and 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

Public availability, access and reading status by material
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

Material type: Kim mixed-product/LDL-stability search lead
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 stored 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.
Study overlap and 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

Public availability, access and reading status by material
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

Material type: 2026 guideline key-messages search lead
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 stored 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.
Study overlap and 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

Public availability, access and reading status by material
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.

Report counts versus independent study counts

This list links materials that may overlap. The six groups do not mean six independent clinical trials. S101, S102: F101: excluded from direct scoring; directly eligible=False / S103, S104: F102: excluded from direct scoring; directly eligible=False / S105, S106: F103: excluded from direct scoring; directly eligible=False / L366-1, L366-2, L366-3, S101, S102: pantethine original trials/review and Evans full text/abstract; inclusion in the previous bibliography/cohort relationships remain unresolved, independent-participant summations performed: 0 / L028, L3099: same/adjacent ingredients in different skin/acne questions; not direct LDL-C families / S06, S107, S108, S109: official nutrition/safety, mixed products/different endpoints, and domain search leads; not counted as repeated LDL-C monotherapy trials. S101 PMC and S102 PubMed concern the same Evans pantethine trial. Cohort relationships in other bibliographic records are unverified. Report counts are not summed as independent trial counts or total participant counts.

Review criteria

Version NGM-v3100-SOLE-ORAL-B5-ELEVATED-LDL-C-1.0 · Criteria record date 2026-10-05. These are Chamgap's own application conditions, informed by the referenced methods. They do not constitute official assessment-tool certification or a new efficacy score.

N01 · Which ingredient, population, and LDL-C comparison?

Required materials and conditions: Adults with elevated LDL-C, oral B5 monotherapy, comparator with the same background treatment, between-group change in LDL-C
Conditions for verification: Link the current original effect wording and inclusion/exclusion boundaries to exact locations.
Requirement and applicability: Required (selected B5 monotherapy and LDL-C comparison)
Application exceptions: Pantethine, multicomponent products, acne, and clinical events are separate questions.
Why this condition is needed: Needed to avoid combining all lipid-related efficacy claims for the ingredient into a single question.
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

N02 · Are pantothenic acid and pantethine the same intervention?

Required materials and conditions: Exact molecule, salt, active ingredient, and route of administration
Conditions for verification: Link differences in substance, combination, and route to the original text and explain the limits of direct attribution.
Requirement and applicability: Required (selected B5 monotherapy and LDL-C comparison)
Application exceptions: Verify the exact salt of calcium pantothenate separately and perform no new mass conversion.
Why this condition is needed: Needed to avoid transferring clinical results solely on the basis of a description as a derivative.
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

N03 · Are the origin, salt, and formulation of an eligible single-active-ingredient product known?

Required materials and conditions: Manufacturing origin, brand, exact salt, purity, batch, tablet/capsule, and release type
Conditions for verification: Distinguish verified values for a directly eligible formulation from unverified product items.
Requirement and applicability: Required (selected B5 monotherapy and LDL-C comparison)
Application exceptions: An oral single-active-ingredient product specified in the question is not an actual product specification.
Why this condition is needed: Needed to avoid inserting the specifications of another molecule or multicomponent product into those of the directly relevant product.
Referenced methods: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptation to laboratory tests are internally designed

N04 · What are the actual dose and total exposure for B5 monotherapy?

Required materials and conditions: Single-active-ingredient dose, frequency, active amount, dietary/concurrent supplementation, and adherence
Conditions for verification: Verify the directly eligible dose and actual total exposure, leaving unavailable values unfilled.
Requirement and applicability: Required (selected B5 monotherapy and LDL-C comparison)
Application exceptions: The 600/900 mg pantethine doses, nutritional reference values, and examples of high-dose harms are separate records.
Why this condition is needed: Needed to avoid using the pantethine dose as a pantothenic-acid treatment dose.
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

N05 · Have the directly relevant treatment duration and assessment time points been verified?

Required materials and conditions: Single-active-ingredient administration duration, planned/actual LDL-C time points, and follow-up
Conditions for verification: Distinguish eligible single-active-ingredient durations and time points from the duration of a related trial.
Requirement and applicability: Required (selected B5 monotherapy and LDL-C comparison)
Application exceptions: Do not arbitrarily specify a universal minimum treatment duration.
Why this condition is needed: Needed to avoid using 16 weeks for another substance as a verified value for the single-active-ingredient treatment.
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

N06 · How were adults with elevated LDL-C selected?

Required materials and conditions: Diagnostic threshold, baseline LDL-C, age, inclusion/exclusion, and setting
Conditions for verification: Explain the actual recruitment/diagnosis in directly eligible studies and what remains unverified.
Requirement and applicability: Required (selected B5 monotherapy and LDL-C comparison)
Application exceptions: Do not transfer the cardiovascular-risk and statin-eligible population of a pantethine trial to the single-active-ingredient population.
Why this condition is needed: Needed to avoid mistaking the population label in the question for actual recruitment criteria.
Referenced methods: M03 §3.2.1; detailed population conditions are internally designed

N07 · Can lipid-lowering medications, diet, deficiency, and other supplementation be distinguished?

Required materials and conditions: Arm-specific lipid-lowering medications, diet, deficiency/nutritional status, and concurrent supplementation
Conditions for verification: Link the scope and limitations of baseline/concomitant-treatment verification in eligible single-active-ingredient studies.
Requirement and applicability: Required (selected B5 monotherapy and LDL-C comparison)
Application exceptions: If baseline deficiency is unverified, do not establish that deficiency is absent.
Why this condition is needed: Needed to avoid using differences in background treatment and correction of deficiency as an additional B5 effect.
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

N08 · What are the placebo or usual care and the actual shared treatment?

Required materials and conditions: Actual placebo composition, usual care, rescue treatment, and arm-specific changes
Conditions for verification: Distinguish the actual comparison, differences other than the intervention, and their implications for analysis.
Requirement and applicability: Required (selected B5 monotherapy and LDL-C comparison)
Application exceptions: Do not require all changes in both arms to be identical; examine them in relation to the effect of interest.
Why this condition is needed: Needed to avoid using the planned comparison as verification of the actual comparator arm.
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

N09 · Were directly measured LDL and formula-calculated LDL distinguished?

Required materials and conditions: LDL measurement method, specimen/blood collection, calculation formula, and arm-specific procedures
Conditions for verification: Explain the actual measurement conditions for eligible LDL-C results and the scope that cannot be verified.
Requirement and applicability: Required (selected B5 monotherapy and LDL-C comparison)
Application exceptions: Do not convert other lipid markers or oxidative stability into LDL-C concentration.
Why this condition is needed: Needed to avoid establishing that values from different measurement methods represent the same endpoint.
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

N10 · Are differences in change, endpoint differences, and percentages the same value?

Required materials and conditions: LDL-C definition, units, baseline/change/endpoint values, and between-group/within-group distinctions
Conditions for verification: Separate the selected between-group change in concentration from the different measures in related reports.
Requirement and applicability: Required (selected B5 monotherapy and LDL-C comparison)
Application exceptions: Perform no new conversion between mg/dL and mmol/L.
Why this condition is needed: Needed to avoid converting within-group percentages into placebo-adjusted concentration differences.
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

N11 · What intervention effect does an eligible analysis estimate?

Required materials and conditions: Between-group/within-group, change/endpoint, adjustment, ITT/PP, and analysis population
Conditions for verification: Explain how the actual effect definition in directly eligible results agrees with or differs from the question.
Requirement and applicability: Required (selected B5 monotherapy and LDL-C comparison)
Application exceptions: Do not assume ITT or an adjusted effect if no record is available.
Why this condition is needed: Needed to avoid transferring different effect definitions into the same estimate.
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

N12 · Are the directly relevant LDL-C effect, CI, and P value known?

Required materials and conditions: Eligible between-group effect, uncertainty interval, P value, and units
Conditions for verification: Distinguish the unverified direct-effect fields from related results.
Requirement and applicability: Required (selected B5 monotherapy and LDL-C comparison)
Application exceptions: Do not reconstruct pantethine results, other biomarkers, or graphs as a directly relevant effect.
Why this condition is needed: Needed to avoid converting an unverified result into an effect of 0 or nonsignificance.
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

N13 · How many participants were allocated, measured, analyzed, and completed, respectively?

Required materials and conditions: Arm-specific allocation/analysis/completion for the single-active-ingredient treatment, missing data, and outcome-specific denominators
Conditions for verification: Distinguish directly relevant outcome-specific denominators from what remains unverified.
Requirement and applicability: Required (selected B5 monotherapy and LDL-C comparison)
Application exceptions: 32 allocated and 24 completed are denominators from the pantethine trial.
Why this condition is needed: Needed to avoid using related sample sizes as directly relevant LDL-C analysis denominators.
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

N14 · Are the design, concealment, and blinding of the monotherapy comparison known?

Required materials and conditions: Actual design, allocation/concealment, baseline balance, and assessment procedures
Conditions for verification: Link the actual design/assessment information and limitations of the directly selected results.
Requirement and applicability: Required (selected B5 monotherapy and LDL-C comparison)
Application exceptions: Do not mark crossover or cluster designs as not applicable when the design is unverified.
Why this condition is needed: Needed to avoid using a triple-blind label from a related study as a direct B5 bias assessment.
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

N15 · Are adherence, rescue treatment, analysis populations, and missing-data handling known?

Required materials and conditions: Actual intake, discontinuation, arm-specific changes, ITT/PP, and missing-data handling
Conditions for verification: Distinguish directly eligible information on adherence, withdrawals, and analysis from what remains unverified.
Requirement and applicability: Required (selected B5 monotherapy and LDL-C comparison)
Application exceptions: Do not arbitrarily fill in analysis methods absent from the original text.
Why this condition is needed: Needed to avoid mixing the effect of assignment with before-and-after effects among adherent participants/completers.
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

N16 · What magnitudes of difference does the reported interval allow?

Required materials and conditions: Direct effect/CI, variance, and a justified important difference
Conditions for verification: Explain the relationship between the reported interval and the importance criterion, or why it cannot be interpreted.
Requirement and applicability: Required (selected B5 monotherapy and LDL-C comparison)
Application exceptions: Do not arbitrarily adopt a common minimum sample size, duration, or MCID.
Why this condition is needed: Needed to avoid declaring sufficiency based only on sample size, statistical significance, or the number of trials.
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

N17 · What produced the LDL-C improvement in Evans?

Required materials and conditions: Actual ingredients, within-arm changes, time points, and original tables from the pantethine trial
Conditions for verification: Explain the measure, duration, and substance in the positive report together with the reason for its direct ineligibility.
Requirement and applicability: Required (selected B5 monotherapy and LDL-C comparison)
Application exceptions: Do not calculate a new between-group effect from the two changes from baseline.
Why this condition is needed: Needed to preserve attribution to a different molecule without concealing favorable results.
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

N18 · Are P=0.006 and P=0.010 the same comparison?

Required materials and conditions: Concentration comparison, percentage-change comparison, actual analysis, and time points
Conditions for verification: Preserve the P values for the comparisons distinguished in the original text, their attribution, and the unverified aspects.
Requirement and applicability: Required (selected B5 monotherapy and LDL-C comparison)
Application exceptions: Do not convert a P value into an effect size or CI.
Why this condition is needed: Needed to avoid merging distinct reported tests into one.
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

N19 · What do 32 allocated and 24 completed mean?

Required materials and conditions: Evans allocation, completion, analyses by arm/endpoint, and reasons for dropout
Conditions for verification: Preserve the related trial's original denominators and explain the unverified aspects of the direct/arm-specific analyses.
Requirement and applicability: Required (selected B5 monotherapy and LDL-C comparison)
Application exceptions: Do not calculate new arm-specific dropout counts or rates from the difference.
Why this condition is needed: Needed to avoid treating the overall allocation/completion counts as the same analysis denominator.
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

N20 · Are PMC and PubMed independent replication trials?

Required materials and conditions: S101/S102 DOI, PMID, trial, and outcome linkage
Conditions for verification: Distinguish verified links between reports of the same study from unresolved families.
Requirement and applicability: Required (selected B5 monotherapy and LDL-C comparison)
Application exceptions: Do not automatically establish that other references concern the same cohort or independent trials.
Why this condition is needed: Needed to avoid counting reports as unique trials.
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

N21 · Were Evans's funding and independent replication verified?

Required materials and conditions: Reported funding, product/author relationships, institutions, and family linkage
Conditions for verification: Explain the verified funding and the scope of unverified disclosures/independence.
Requirement and applicability: Required (selected B5 monotherapy and LDL-C comparison)
Application exceptions: Do not automatically exclude results because funding was provided.
Why this condition is needed: Needed to avoid turning original funding reports into independent funding or absence of bias.
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

N22 · Do mouse/adipocyte results answer the question about human LDL-C?

Required materials and conditions: Species, sex, experimental system, measured endpoints, and whether a human comparison exists
Conditions for verification: Explain the difference between the actual nonhuman subjects and the direct human question.
Requirement and applicability: Required (selected B5 monotherapy and LDL-C comparison)
Application exceptions: Preserve nonhuman studies within their scope without deleting them.
Why this condition is needed: Needed to avoid transferring mechanistic observations to a human lipid effect of a single active ingredient.
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

N23 · Are S103 and S104 the same study?

Required materials and conditions: Relationships among the preprint/paper, authors, experiments, and versions
Conditions for verification: Distinguish the preserved possible relationship, verified identifiers, and remaining gaps.
Requirement and applicability: Required (selected B5 monotherapy and LDL-C comparison)
Application exceptions: Do not establish that studies are identical solely from similar titles.
Why this condition is needed: Needed to avoid summing a possibly related preprint as an independent 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

N24 · Is the NCT03444155 protocol a single-active-ingredient B5 result?

Required materials and conditions: Protocol version, combination composition, comparator, administration plan, and actual results
Conditions for verification: Explain the attribution of the actual combination protocol and the unverified single-active-ingredient results.
Requirement and applicability: Required (selected B5 monotherapy and LDL-C comparison)
Application exceptions: A record of protocol access does not verify actual allocation or results.
Why this condition is needed: Needed to distinguish plans from results and contributions within a combination.
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

N25 · Were the planned endpoint and reporting for the selected LDL-C outcome compared?

Required materials and conditions: Directly eligible registration, protocol, SAP, and actual reporting/changes
Conditions for verification: Indicate the actual scope of plan/report comparison for the direct comparison and the aspects not compared.
Requirement and applicability: Required (selected B5 monotherapy and LDL-C comparison)
Application exceptions: Do not turn failure to acquire material into confirmation of nonregistration or selective reporting.
Why this condition is needed: Needed to identify the material required to check whether only favorable analyses were selected.
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

N26 · Are the three references from the previous 366 direct B5 replications?

Required materials and conditions: Gaddi/Rumberger original trials, McRae review, molecules, and included study families
Conditions for verification: Distinguish each material type, molecule, and unverified results/families.
Requirement and applicability: Required (selected B5 monotherapy and LDL-C comparison)
Application exceptions: Do not carry over the previous C and 52 points to the new question.
Why this condition is needed: Needed to avoid summing earlier references, reviews, and trials as independent single-active-ingredient B5 replications.
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

N27 · Are skin 028 and acne 3099 LDL-C results?

Required materials and conditions: Identity, endpoints, and linkage of the earlier composite skin/hair and acne questions
Conditions for verification: Preserve the differences between the original related questions and the selected LDL-C endpoint, and the reading gaps.
Requirement and applicability: Required (selected B5 monotherapy and LDL-C comparison)
Application exceptions: Reading the reference records in 3100 differs from directly reading the earlier original files.
Why this condition is needed: Needed to avoid merging different outcomes for the same ingredient into this efficacy question.
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

N28 · What is the scope of the S107/S108/S109 materials?

Required materials and conditions: Article identifiers, product composition, concentration/oxidative stability, and guideline full texts
Conditions for verification: Explain each lead's material type, different question, and unverified results.
Requirement and applicability: Required (selected B5 monotherapy and LDL-C comparison)
Application exceptions: Do not count inaccessible materials as negative trials.
Why this condition is needed: Needed to avoid turning search titles, access failures, and domain addresses into direct clinical results.
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

N29 · Does an unverified direct result mean an effect of 0 or worldwide absence?

Required materials and conditions: Verified direct/adjacent and positive/other results, and search scope/failures
Conditions for verification: Explain attribution of all verified results and the limited scope of unverified direct evidence.
Requirement and applicability: Required (selected B5 monotherapy and LDL-C comparison)
Application exceptions: Do not turn access failures and incomplete searching into negative studies or 0 studies.
Why this condition is needed: Needed to avoid extending the finding to no effect, refutation, or absence of all studies worldwide.
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

N30 · Were current summaries distinguished from historical full-text access?

Required materials and conditions: Publication, attempted/successful access, acquisition, reading, and actual dates and locations 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.
Requirement and applicability: Required (selected B5 monotherapy and LDL-C comparison)
Application exceptions: Do not label unattempted access as failed access or infer access dates from the overall review date.
Why this condition is needed: Needed to avoid turning historical access_level into original-paper reading in this review.
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

N31 · Are the original grade, score, and axes new condition statuses?

Required materials and conditions: Original ?, empty values, B/S, unscored subsequent axes/strength, and gate/original calculation
Conditions for verification: Preserve the original judgment values as quotations and distinguish them from conditions being met in the new table.
Requirement and applicability: Required (selected B5 monotherapy and LDL-C comparison)
Application exceptions: The conditional record of the original C cap is also not an application or a new calculation in this review.
Why this condition is needed: Needed to avoid elevating an earlier score or an absence gate into a new judgment.
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

N32 · Does an LDL-C difference answer questions about cardiovascular events or medication replacement?

Required materials and conditions: Boundary between the selected laboratory result and questions about events/treatment replacement
Conditions for verification: Distinguish the original question from a separate extension to clinical events.
Requirement and applicability: Supplementary (boundary for extension to clinical events)
Application exceptions: An event trial is not imposed as an additional requirement for the LDL-C concentration question itself.
Why this condition is needed: Needed to prevent automatic extension from a surrogate marker to prevention of clinical events.
Referenced methods: M03 §3.2.4; extension boundary specified by the author

N33 · Does the evidence answer questions about optimal dose, persistence after discontinuation, and all subgroups?

Required materials and conditions: Direct dose comparisons, discontinuation/long-term follow-up, and prespecified subgroups/interactions
Conditions for verification: Separately distinguish extensions to dose/persistence and populations that are absent from direct comparisons.
Requirement and applicability: Supplementary (extensions to dose, persistence, and populations)
Application exceptions: Extension studies are not imposed as requirements for the current question as a whole.
Why this condition is needed: Needed to prevent extension of the narrow concentration question to optimal dose, persistence, or efficacy in all populations.
Referenced methods: M03 §3.2.1–3.2.4; details on dose, persistence, and effect modification use the author's own design

N34 · Do high-dose harms and nutritional reference values establish a lipid-treatment dose?

Required materials and conditions: Harms involving the same ingredient, exposure, denominator/duration, collection, and nutritional reference values
Conditions for verification: Distinguish the original harm/nutrition descriptions from gaps in safety evidence from direct comparisons.
Requirement and applicability: Required (selected B5 monotherapy and LDL-C comparison)
Application exceptions: The 10 g/day example is not a toxicity threshold/recommendation, and 5 mg/day is the adult adequate intake.
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.
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

N35 · Has safety been verified for long-term high-dose use, concomitant use, and vulnerable populations?

Required materials and conditions: Long-term use for LDL-C, pregnancy/lactation, children, liver/kidney disease, and concomitant use
Conditions for verification: Indicate the limits of direct safety evidence for the selected purpose and gaps in populations/durations.
Requirement and applicability: Supplementary (extension to long-term/concomitant-use safety)
Application exceptions: No known important interactions does not mean that all interactions have been excluded.
Why this condition is needed: Needed to prevent limited general records from being extended to safety in all populations/combinations.
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

N36 · What can change, as of which date and within which scope?

Required materials and conditions: Original evidence/review dates, actual current review, search scope, and new data/corrections/retractions
Conditions for verification: Separate the original dates and review/access levels from activities not currently performed and the conditions for updates.
Requirement and applicability: Required (selected B5 monotherapy and LDL-C comparison)
Application exceptions: first_published_at is an editorial reference date, not proof of actual server publication.
Why this condition is needed: Needed to avoid overstating this conversion as a current comprehensive search, publication, or independent clinical certification.
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

Referenced methods and the sections actually reviewed

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

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

Referenced principle: Clearly record the question, eligibility conditions, and reasons for changes, and distinguish variations of the intervention.
Extent of review: 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

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

Referenced principle: Distinguish and link studies and reports, and do not omit a study merely because an outcome is unreported.
Extent of review: 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

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

Referenced principle: Fix the outcome and effect of interest, and review randomization, deviations, missingness, measurement, and selective reporting.
Extent of review: 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

Official methodology · §15.2.4, §15.3.1–15.3.3

Referenced principle: Distinguish effect estimates, intervals, importance, and applicability. Sample size alone does not determine precision.
Extent of review: 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

Official methodology · §19.1.2, §19.2.1–19.2.4

Referenced principle: A harm question may require designs, populations, and follow-up different from those for efficacy. Case reports do not establish incidence rates.
Extent of review: 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/material version 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.

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

Researcher downloads

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

View all item details

N01 · Which ingredient, population, and LDL-C comparison?

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.
Verification status: Met
Materials actually read: The complete, exactly retained archived summary was actually read; the linked original material was not read in this review
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.
Remaining uncertainty: This verifies the identity of the question, not direct efficacy.
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.
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?

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.
Verification status: Met
Materials actually read: The complete, exactly retained archived summary was actually read; the linked original material was not read in this review
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.
Remaining uncertainty: Verifying the substance boundary is separate from verifying the specifications of an eligible product.
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.
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?

Current findings: The origin, brand, salt, purity, batch, formulation, and release type of an eligible pantothenic-acid single-active-ingredient product are unverified.
Verification status: Unverified
Materials actually read: The complete, exactly retained archived summary was actually read; the linked original material was not read in this review
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.
Remaining uncertainty: Specifications not supplied by the current material were not taken from related products.
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.
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?

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.
Verification status: Unverified
Materials actually read: The complete, exactly retained archived summary was actually read; the linked original material was not read in this review
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.
Remaining uncertainty: No new calcium-salt mass conversion or personal dosage was created.
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.
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?

Current findings: Eligible monotherapy treatment duration and LDL-C assessment time points are unverified. 16 weeks is the duration of the Evans pantethine trial.
Verification status: Unverified
Materials actually read: The complete, exactly retained archived summary was actually read; the linked original material was not read in this review
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.
Remaining uncertainty: Duration for a different molecule does not meet the selected comparison.
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.
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?

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.
Verification status: Unverified
Materials actually read: The complete, exactly retained archived summary was actually read; the linked original material was not read in this review
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.
Remaining uncertainty: The population of a related trial is attributed only to that trial.
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.
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?

Current findings: Medication, deficiency, and dietary/concurrent-supplementation status in the directly eligible population are unverified.
Verification status: Unverified
Materials actually read: The complete, exactly retained archived summary was actually read; the linked original material was not read in this review
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.
Remaining uncertainty: The description of a diet-controlled pantethine study is not a concomitant-treatment condition in the selected B5 trial.
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.
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?

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.
Verification status: Unverified
Materials actually read: The complete, exactly retained archived summary was actually read; the linked original material was not read in this review
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.
Remaining uncertainty: A comparison of two B-complex formulations is not a placebo comparison of B5 monotherapy.
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.
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?

Current findings: There is no information to distinguish directly measured LDL from formula-calculated LDL, and measurement procedures in eligible monotherapy trials are unverified.
Verification status: Unverified
Materials actually read: The complete, exactly retained archived summary was actually read; the linked original material was not read in this review
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.
Remaining uncertainty: Measurement information or results were not filled in through unit conversion or graph reconstruction.
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.
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?

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.
Verification status: Met
Materials actually read: The complete, exactly retained archived summary was actually read; the linked original material was not read in this review
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.
Remaining uncertainty: This verifies the distinction between measures; it does not mean that single-active-ingredient results were obtained.
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.
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?

Current findings: Baseline, change, and endpoint values and actual between-group analyses for B5 monotherapy are unverified.
Verification status: Unverified
Materials actually read: The complete, exactly retained archived summary was actually read; the linked original material was not read in this review
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.
Remaining uncertainty: Do not fill a direct B5 estimate with related pantethine analyses.
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.
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?

Current findings: Within primary_effect, the records for mean_difference, confidence_interval, p_value, and analysis sample size are empty/not_verified.
Verification status: Unverified
Materials actually read: The complete, exactly retained archived summary was actually read; the linked original material was not read in this review
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.
Remaining uncertainty: This does not confirm an effect of 0, equivalence, or the absence of a directly relevant effect.
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.
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?

Current findings: Arm-specific LDL-C analysis denominators and allocated/completed counts in eligible B5 monotherapy trials are unverified.
Verification status: Unverified
Materials actually read: The complete, exactly retained archived summary was actually read; the linked original material was not read in this review
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.
Remaining uncertainty: Denominators from related studies were not transferred, and no new missing counts or rates were calculated.
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.
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?

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.
Verification status: Unverified
Materials actually read: The complete, exactly retained archived summary was actually read; the linked original material was not read in this review
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.
Remaining uncertainty: Do not label this as formal execution of RoB 2 or absence of bias.
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.
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?

Current findings: Adherence to the single-active-ingredient product, withdrawals by arm, analysis populations, and handling of missing data are unverified.
Verification status: Unverified
Materials actually read: The complete, exactly retained archived summary was actually read; the linked original material was not read in this review
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.
Remaining uncertainty: Pantethine allocation/completion counts alone do not reveal how the selected results were handled.
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.
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?

Current findings: The direct LDL-C CI, variance, and important-difference criterion are unverified, and the original precision axis is an unscored empty value.
Verification status: Unverified
Materials actually read: The complete, exactly retained archived summary was actually read; the linked original material was not read in this review
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.
Remaining uncertainty: Do not use an unverified interval to exclude an important effect or create a new grade.
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.
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?

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.
Verification status: Partly verified
Materials actually read: The complete, exactly retained archived summary was actually read; the linked original material was not read in this review
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.
Remaining uncertainty: The complete original results tables and a single-active-ingredient B5 estimate are unverified in this review.
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.
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?

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.
Verification status: Partly verified
Materials actually read: The complete, exactly retained archived summary was actually read; the linked original material was not read in this review
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.
Remaining uncertainty: The direct B5 P value is empty, and the detailed analyses for the two tests were not newly verified.
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.
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?

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.
Verification status: Partly verified
Materials actually read: The complete, exactly retained archived summary was actually read; the linked original material was not read in this review
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.
Remaining uncertainty: Arm-specific LDL-C analysis denominators and the reasons for and handling of dropouts are unverified in the preserved text.
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.
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?

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.
Verification status: Partly verified
Materials actually read: The complete, exactly retained archived summary was actually read; the linked original material was not read in this review
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.
Remaining uncertainty: Participant links with the other pantethine references were not verified in these materials.
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.
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?

Current findings: The Evans pantethine trial was recorded as funded by Daiichi Fine Chemical Co Ltd.
Verification status: Partly verified
Materials actually read: The complete, exactly retained archived summary was actually read; the linked original material was not read in this review
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.
Remaining uncertainty: This information belongs to pantethine and does not establish independent funding for direct B5 evidence or all conflicts of interest.
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.
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?

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.
Verification status: Partly verified
Materials actually read: The complete, exactly retained archived summary was actually read; the linked original material was not read in this review
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.
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.
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.
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?

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.
Verification status: Unverified
Materials actually read: The complete, exactly retained archived summary was actually read; the linked original material was not read in this review
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.
Remaining uncertainty: S104 was not counted as a new independent human trial or a verified nonhuman replication.
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.
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?

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.
Verification status: Partly verified
Materials actually read: The complete, exactly retained archived summary was actually read; the linked original material was not read in this review
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.
Remaining uncertainty: The multicomponent protocol and registration were not counted as eligible single-active-ingredient trials.
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.
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?

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.
Verification status: Unverified
Materials actually read: The complete, exactly retained archived summary was actually read; the linked original material was not read in this review
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.
Remaining uncertainty: Do not assess selective reporting for the direct single-active-ingredient question from partial reading of the combination S105 protocol.
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.
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?

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.
Verification status: Partly verified
Materials actually read: The complete, exactly retained archived summary was actually read; the linked original material was not read in this review
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.
Remaining uncertainty: The earlier original files, external paper results, and cohort links with Evans were not read/are unverified in this review.
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.
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?

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.
Verification status: Partly verified
Materials actually read: The complete, exactly retained archived summary was actually read; the linked original material was not read in this review
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.
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.
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.
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?

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.
Verification status: Partly verified
Materials actually read: The complete, exactly retained archived summary was actually read; the linked original material was not read in this review
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.
Remaining uncertainty: The existence of a lead does not verify individual results or current guideline content.
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.
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?

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.
Verification status: Met
Materials actually read: The complete, exactly retained archived summary was actually read; the linked original material was not read in this review
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.
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.
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.
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?

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.
Verification status: Met
Materials actually read: The complete, exactly retained archived summary was actually read; the linked original material was 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.
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.
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.
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?

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.
Verification status: Met
Materials actually read: The complete, exactly retained archived summary was actually read; the linked original material was not read in this review
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.
Remaining uncertainty: No new efficacy grade, score, probability, or clinical calculation was produced.
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.
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?

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.
Verification status: Not applicable
Materials actually read: The complete, exactly retained archived summary was actually read; the linked original material was not read in this review
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.
Remaining uncertainty: This nonapplicability does not substitute for unverified direct LDL-C data.
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.
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?

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.
Verification status: Not applicable
Materials actually read: The complete, exactly retained archived summary was actually read; the linked original material was not read in this review
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.
Remaining uncertainty: Gaps in directly eligible dose, duration, and population remain unchanged in their corresponding rows.
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.
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?

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.
Verification status: Partly verified
Materials actually read: The complete, exactly retained archived summary was actually read; the linked original material was not read in this review
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.
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.
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.
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?

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.
Verification status: Unverified
Materials actually read: The complete, exactly retained archived summary was actually read; the linked original material was not read in this review
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.
Remaining uncertainty: Do not convert research or nutritional values into personal dosing instructions.
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.
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?

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.
Verification status: Met
Materials actually read: The complete, exactly retained archived summary was actually read; the linked original material was not read in this review
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.
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.
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.
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