Oral pantothenic acid (vitamin B5) as the sole active ingredient × Reduction of FSS fatigue severity in adults with unexplained/nonspecific persistent fatigue

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 fatigue, intervention, and FSS comparison?Required (selected B5 monotherapy comparison for FSS in nonspecific persistent fatigue)	The selected question is whether oral treatment with pantothenic acid as the sole active ingredient lowers FSS more than placebo or usual care on the same background treatment in adults with unexplained/nonspecific persistent fatigue. subclaims is an empty list. S201 S202 S204 S205 S207	This verifies the identity of the question, not an effect or the absence of all human studies.	Adults with nonspecific persistent fatigue, oral B5 as the sole active ingredient, comparator on the same background treatment, and between-group FSS results	Compare differences in population, intervention, and endpoint between the existing question and candidate results for each material.
2	Unverified	Full text not readStored summary read	N02 · Population criteriaHow was the population with unexplained persistent fatigue defined?Required (selected B5 monotherapy comparison for FSS in nonspecific persistent fatigue)	The population was fixed to adults with unexplained/nonspecific persistent fatigue, but diagnosis, baseline nutrition/deficiency, and exclusion criteria in eligible monotherapy trials were not verified. S201 S205 S207 S213	The population specified in the question does not substitute for actual recruitment criteria in an eligible study.	Diagnosis, exclusion tests, age, underlying diseases, and selection criteria	Obtain recruitment and diagnostic tables for the target population and compare applicability boundaries with groups with other causes.
3	Unverified	Full text not readStored summary read	N03 · Persistence criteriaAre fatigue duration and baseline severity known?Required (selected B5 monotherapy comparison for FSS in nonspecific persistent fatigue)	The fatigue-duration criterion and baseline FSS in a directly relevant monotherapy trial are unverified within the preserved scope. S201 S202	Do not fill in the duration for the selected question solely from the prolonged fatigue label in a related product trial.	Fatigue-duration threshold, baseline FSS, and distribution by severity	Link recruitment criteria and baseline tables to time points/scale versions to review eligibility.
4	Met	Full text not readStored summary read	N04 · Intervention identityWere B5 monotherapy and other molecules or multicomponent products distinguished?Required (selected B5 monotherapy comparison for FSS in nonspecific persistent fatigue)	The question concerns oral B5 as the sole active ingredient. Pantethine, pantetheine, dexpanthenol/panthenol, B-complex products, multivitamins, and multicomponent energy products were distinguished from the direct intervention. The exact eligible salt is unverified. S06 S201 S205 S207 S213	This verifies the distinction between boundaries; it does not mean that a specific single-active-ingredient product was acquired.	Documentation of pantothenic acid, the exact salt, other active ingredients, and route	Compare manufacturing-composition and chemical-form documents for each result to verify sole-active-ingredient status.
5	Unverified	Full text not readStored summary read	N05 · Product specificationsAre the origin, quality, and formulation of an eligible single-active-ingredient product known?Required (selected B5 monotherapy comparison for FSS in nonspecific persistent fatigue)	Origin, salt, brand, purity, batch, formulation, and release type are unverified in eligible monotherapy trials. S201 S202 S203 S213	Esserre or Swisse brand information belongs to the respective multicomponent product.	Exact salt, origin, purity, batch, brand, release type, and excipients	Verify formulation specifications, active-ingredient analyses, and batch records for the eligible comparison together with the results.
6	Unverified	Full text not readStored summary read	N06 · Dose and frequencyWhat are the directly eligible B5 dose and actual total exposure?Required (selected B5 monotherapy comparison for FSS in nonspecific persistent fatigue)	The eligible monotherapy dose and frequency are unverified. Calcium pantothenate 10 g/day in the lupus cases and NIH nutritional reference values do not fill in a directly relevant fatigue-treatment dose. S06 S207	Nominal or actual amounts and salt conversions were not arbitrarily generated.	Single-active-ingredient product dose, frequency, salt mass, dietary/concurrent supplementation, and actual intake	Obtain administration, adherence, and dietary-exposure records from a comparative monotherapy trial to assess actual exposure.
7	Unverified	Full text not readStored summary read	N07 · Duration and time pointsHave eligible treatment duration and FSS assessment time points been specified?Required (selected B5 monotherapy comparison for FSS in nonspecific persistent fatigue)	Eligible monotherapy treatment duration and assessment time points are unverified. Assessments at 28 days and 56 days and follow-up visits for Ullah's multicomponent product were preserved as distinct. S201 S202	A different formulation's schedule does not verify duration for the selected question.	Treatment duration, planned endpoint time points, follow-up, and discontinuation time points	Collect plans, actual administration duration, and each follow-up result separately and compare them with prespecified endpoints.
8	Unverified	Full text not readStored summary read	N08 · Comparator and background treatmentAre placebo or usual care and common treatment actually the same?Required (selected B5 monotherapy comparison for FSS in nonspecific persistent fatigue)	Placebo or usual care on identical background treatment is the planned comparison. Placebo composition, common treatment, and rescue medication in eligible monotherapy trials are unverified. S201 S205 S207	The presence of a control arm in a multicomponent trial alone does not meet the monotherapy comparison conditions.	Placebo composition, background treatment, rescue medication, and arm-specific changes	Compare arm-specific prescription, placebo, rescue-treatment, and change records for the eligible comparison against the analysis plan.
9	Unverified	Full text not readStored summary read	N09 · Baseline nutritionCan diet, deficiency, and concurrent supplementation be distinguished?Required (selected B5 monotherapy comparison for FSS in nonspecific persistent fatigue)	Baseline nutrition and deficiency status in eligible monotherapy trials are unverified. Deficiency case reports and the nonspecific-fatigue question are separate. S211 S06	Do not fill in baseline information with mechanisms or blood markers.	Baseline nutrition, B5-deficiency testing, diet, and concurrent active ingredients	Obtain baseline nutrition, deficiency measurements, and concurrent-supplementation information by arm to review applicability.
10	Unverified	Full text not readStored summary read	N10 · FSS versionHave the actual FSS version, range, and scoring method been verified?Required (selected B5 monotherapy comparison for FSS in nonspecific persistent fatigue)	FSS is the prioritized scale for this question. Its actual version, range, and scoring method in an eligible monotherapy trial are unverified. S201 S202 S205 S213	An FSS label does not mean that all measurement conditions have been verified.	Actual FSS version, items/range, aggregation, direction, and measurement procedures	Compare the actual scale version and scoring/collection procedures against results tables and blinding information.
11	Met	Full text not readStored summary read	N11 · Endpoint attributionAre FSS, CIS, Chalder, and mechanisms the same outcome?Required (selected B5 monotherapy comparison for FSS in nonspecific persistent fatigue)	FSS for Ullah's multicomponent product, CIS for the CFS multicomponent product, the secondary Chalder endpoint in the healthy-women registration, and animal/metabolic and exercise markers were distinguished. S201 S202 S204 S205 S210 S213 S216	Improvement in related symptoms or mechanistic observations does not substitute for the FSS effect of B5 alone.	Scale, primary/secondary endpoint, time point, population, and intervention for each material	Compare the original definitions of different scales and planned endpoints, and do not merge them into a common effect.
12	Unverified	Full text not readStored summary read	N12 · Effect of interestWere between-group differences in change distinguished from endpoint differences and within-group differences?Required (selected B5 monotherapy comparison for FSS in nonspecific persistent fatigue)	The question was fixed to prioritize the between-group difference in change in FSS, with endpoint differences separate, but monotherapy baseline, change, and endpoint values and the actual analysis are unverified. S201 S205 S207	Do not estimate a between-group monotherapy effect from improvement with a multicomponent product or subjective lupus narratives.	Baseline, change, and endpoint values, definition of between-group comparison, and adjustment/analysis methods	Compare eligible results tables against the analysis plan to verify estimates and denominators for the effect of interest.
13	Unverified	Full text not readStored summary read	N13 · Effect estimate and intervalAre the directly relevant FSS effect, CI, and P value known?Required (selected B5 monotherapy comparison for FSS in nonspecific persistent fatigue)	The primary_effect.mean_difference, confidence_interval, p_value, and analysis sample-size records are empty/not_verified. S201 S205 S207	No graphs, correlations, variances, or effect estimates were newly calculated or reconstructed.	Eligible between-group effect, uncertainty interval, P value, and units	Obtain estimates, intervals, variances, and denominators from the original results tables and attribute them to the reported effect definition.
14	Unverified	Full text not readStored summary read	N14 · Directly relevant analysis denominatorsHow many participants were allocated, analyzed, and completed, respectively?Required (selected B5 monotherapy comparison for FSS in nonspecific persistent fatigue)	Arm-specific allocation, FSS analysis, and completion denominators in directly eligible monotherapy trials are unverified. Known denominators from related trials remain attributed only to each respective study. S201 S202 S204 S205	No effect or incidence rate was calculated without a denominator.	Arm-specific allocation, analysis, completion, and missing-data/dropout handling in an eligible monotherapy trial	Compare participant flow, reasons for missing data, and outcome-specific analysis tables to verify denominators.
15	Unverified	Full text not readStored summary read	N15 · Allocation and blindingAre allocation, concealment, and assessment procedures in the direct comparison known?Required (selected B5 monotherapy comparison for FSS in nonspecific persistent fatigue)	The preserved materials include related multicomponent-product RCTs, but allocation, concealment, and blinding in a direct monotherapy FSS comparison are unverified. S201 S205	Do not label this as formal execution of RoB 2 or absence of bias.	Actual design, allocation/concealment, baseline balance, and assessor/participant blinding	Review the scope of verification of allocation and outcome measurement using eligible methods, registrations, and baseline/assessment materials.
16	Unverified	Full text not readStored summary read	N16 · Analysis and withdrawalsWere the effects of ITT/PP, adherence, rescue treatment, and missing data verified?Required (selected B5 monotherapy comparison for FSS in nonspecific persistent fatigue)	Adherence, arm-specific analyses, and handling of missing data/rescue treatment in eligible monotherapy trials are unverified. S201 S205	The reporting of completers in a related multicomponent-product trial does not verify missing-data handling for monotherapy results.	Effect of interest, analysis population, adherence, arm-specific changes, and missing-data handling	Match the analysis plan, adherence, and participant flow with results tables to distinguish the actual effect of interest.
17	Unverified	Full text not readStored summary read	N17 · Importance and precisionWhat magnitude of fatigue difference does the interval allow?Required (selected B5 monotherapy comparison for FSS in nonspecific persistent fatigue)	The direct between-group FSS CI, variance, and MCID are unverified. The remaining precision axis is also an unscored empty value in the original material. S201 S205	Do not use an unverified interval as evidence excluding an important effect or establishing an effect of 0.	Direct effect/CI, endpoint-specific variance, and the basis for an MCID	Obtain the basis for an important difference appropriate to the endpoint version and the actual result interval separately, and compare them.
18	Partly verified	Full text not readStored summary read	N18 · Positive combination-product resultsWhat produced the FSS improvement in Ullah?Required (selected B5 monotherapy comparison for FSS in nonspecific persistent fatigue)	Ullah 2023 allocated 58 participants, 29 per arm, to study a product containing pomegranate extract, B-complex vitamins, and vitamin C, and reported FSS improvement. Assessments at 28 days and 56 days were distinguished from follow-up. FSS analysis denominators, completion counts, and the contribution of B5 alone are unverified. S201 S202	The positive combination-product results were neither deleted nor elevated to a direct single-ingredient effect.	Product composition, endpoints, time points, and arm-specific results in the 58-participant trial	Review the combination trial's original tables, composition, and whether individual factors were compared to verify whether an independent B5 contribution can be estimated.
19	Partly verified	Full text not readStored summary read	N19 · Reports of the same trialAre the Ullah full text, abstract, and preliminary evaluation independent replications?Required (selected B5 monotherapy comparison for FSS in nonspecific persistent fatigue)	S201 and S202 are the full text/abstract of the same Ullah RCT and have the same DOI and PMID. S203 is a citation concerning chemical characterization and preliminary evaluation, and the details of its original text are unverified. S201 S202 S203	S203 was not added as an independent single-ingredient FSS trial, and its exact cohort relationship was not established.	S201/S202/S203 report identities, DOI/PMID, and cohort linkage	Trace the registration, recruitment, product, and participant relationships for each report to check for overlap.
20	Partly verified	Full text not readStored summary read	N20 · Combination-product results with no detected differenceDoes nonsignificance in Brouwers mean that B5 alone is ineffective?Required (selected B5 monotherapy comparison for FSS in nonspecific persistent fatigue)	Brouwers 2002 is a trial of a polynutrient supplement in CFS patients and did not report a significant between-group difference in CIS fatigue or other outcomes. It is directly ineligible for the question of B5 alone and FSS. S204 S205	The nonreporting wording in the original evidence.result and the explanation of nonsignificance in the main text are preserved at their respective locations, without converting them into an effect of 0 for the single ingredient.	CIS, design, between-group results, and original tables for the CFS combination product	Check the original CIS results and analysis, composition, and population materials to limit direct attribution to FSS.
21	Partly verified	Full text not readStored summary read	N21 · CFS denominatorsWhat denominators do 53 allocated and 48 completed represent?Required (selected B5 monotherapy comparison for FSS in nonspecific persistent fatigue)	Brouwers allocated 53 participants (27/26), and 48 completed. These are denominators for the CFS combination product, not FSS analysis denominators for B5 alone. S204 S205	No new arm-specific completion counts or direct FSS denominators were estimated beyond the preserved values.	Brouwers arm-specific allocation, completion, outcome-specific analyses, and handling of dropouts	Compare participant flow with the CIS analysis population to verify arm-specific missingness and outcome denominators.
22	Partly verified	Full text not readStored summary read	N22 · Lupus narrativeIs the improvement in 12 people with lupus a single-ingredient comparison?Required (selected B5 monotherapy comparison for FSS in nonspecific persistent fatigue)	The 2007 lupus report is a case series in which 12 women received calcium pantothenate 10 g/day together with several vitamins and combination tablets. It describes subjective fatigue improvement; a concurrent comparator and validated between-group FSS results were not verified. S207	The disease, combined exposure, comparison, and scale all differ from the selected direct question.	Case populations, concomitant prescriptions, comparator, and validated fatigue scale	Check prescriptions, populations, fatigue collection, and the presence of a comparator for each case to examine the limits of causality/direct applicability.
23	Partly verified	Full text not readStored summary read	N23 · Case overlapDo the cases in the 2004 and 2007 lupus reports overlap?Required (selected B5 monotherapy comparison for FSS in nonspecific persistent fatigue)	Whether the cases in the 2004 S206 and 2007 S207 lupus reports overlap is unclear. The preserved original text did not add the samples together. S206 S207	Different journals, years, or URLs are not evidence of independent cases.	Populations, recruitment, case numbers, periods, and linkage in the two reports	Compare case tables and periods in the two original reports and record whether they are the same, different, or unresolved.
24	Partly verified	Full text not readStored summary read	N24 · Repeated citation in reviewsAre the rheumatology reviews separate direct trials?Required (selected B5 monotherapy comparison for FSS in nonspecific persistent fatigue)	S208 and S209 are bibliographic records for reviews concerning rheumatic diseases. Historical review locations identifying the Leung entry, study summaries, and references are preserved. S208 S209 S206 S207	The two DOIs or review averages were not counted as independent replications of B5 alone for FSS.	Original reports included in S208/S209, linkage to Leung, and overlap	Compare family relationships among included-study tables, original reports, and related reviews to link endpoints and repeated citations.
25	Partly verified	Full text not readStored summary read	N25 · A different registered endpointIs Chalder in BEMS a direct FSS result?Required (selected B5 monotherapy comparison for FSS in nonspecific persistent fatigue)	ACTRN12613001087741 is a registered trial of a Swisse multicomponent multivitamin in healthy women aged 50~75. Chalder is a different secondary endpoint, and actual randomized counts and results are unverified. S213	Historical access to the full registration does not mean that the registration was read or direct B5 results were verified in this review.	ACTRN registration, healthy women aged 50~75, multicomponent composition, and endpoint hierarchy/results	Link the registration and results report by exact identity to compare the planned Chalder endpoint with the actual results.
26	Partly verified	Full text not readStored summary read	N26 · Registry-access limitationsDoes a CTG shell mean that results are absent?Required (selected B5 monotherapy comparison for FSS in nonspecific persistent fatigue)	S214 is a mitochondrial cocktail/Gulf War illness lead, and S215 is an Alii combination-product lead; the direct pages at that time were JavaScript shells. S214 S215	They were not labeled as verified full texts/results or counted as negative studies.	Actual text, interventions/endpoints, and results of NCT02804828 and NCT07271316	In an authorized subsequent update, read the registration text and results and compare the exact products and endpoints indicated by the leads.
27	Partly verified	Full text not readStored summary read	N27 · Nonhuman mechanismsDo mouse fatigue and CoA functions constitute an FSS effect in adults?Required (selected B5 monotherapy comparison for FSS in nonspecific persistent fatigue)	S210 is a bibliographic record of original-paper metadata/abstract concerning physical fatigue/cognitive dysfunction in mice. CoA/metabolic functions are not direct FSS effects in adults. S210 S06	Only the preserved metadata/abstract was read; external original experimental tables or effects translated to humans were not verified.	Species, experimental intervention, physiological/behavioral endpoints, and limits of human applicability	State the differences between animal/mechanistic observations and the human clinical question, and do not combine them with direct results.
28	Partly verified	Full text not readStored summary read	N28 · Deficiency case reportsCan B5 deficiency case reports be used for the same fatigue treatment?Required (selected B5 monotherapy comparison for FSS in nonspecific persistent fatigue)	S211 is a J-STAGE abstract/search-index bibliographic record of pantothenic-acid deficiency cases. It is not a comparative FSS result for a single active ingredient in nonspecific persistent fatigue. S211	The existence of human deficiency studies is preserved, but comparisons or effect estimates beyond that abstract are not inferred.	Deficiency diagnosis, correction, population, and assessment endpoints	Check the actual populations, endpoints, and exposures in deficiency/correction cases to examine how they differ from the selected question.
29	Partly verified	Full text not readStored summary read	N29 · Exercise endpointsDoes the older sports-vitamin material answer the FSS question?Required (selected B5 monotherapy comparison for FSS in nonspecific persistent fatigue)	S212 is at the bibliographic/search-abstract level for the early sports-vitamin study with PMID4238715 and DOI10.1007/BF00695017. S212	It was not used as a direct FSS result for B5 alone in nonspecific persistent fatigue.	Product composition, populations, exercise/fatigue endpoints, and actual analyses	Compare the composition, population, and endpoint tables of the original sports trial to record its differences from the direct question.
30	Partly verified	Full text not readStored summary read	N30 · Association and metabolomicsDo ME/CFS metabolomic data represent a single-ingredient treatment effect?Required (selected B5 monotherapy comparison for FSS in nonspecific persistent fatigue)	S216 is a search-index description of ME/CFS metabolomics material, and a CAPTCHA was reported during direct access at that time. S216	The metabolomic bibliography/association was not used as an FSS treatment effect from administering B5 alone.	Direction of exposure, disease, metabolomic findings, and whether a direct intervention exists	Check the direction and comparative design of observational metabolomic data and separate them from the direct FSS intervention question.
31	Partly verified	Full text not readStored summary read	N31 · Patent leadDo patent examples constitute clinical comparative evidence?Required (selected B5 monotherapy comparison for FSS in nonspecific persistent fatigue)	S217 is a search-index bibliographic record of examples in patent US5304574A. S217	Directly eligible between-group FSS results, samples, and independence were not verified from this bibliographic record.	Populations, experiments, and independent clinical results in the US5304574A examples	Compare the relationship between the patent lead and actual clinical reports, including whether they concern the same cases, and verify direct evidence separately.
32	Met	Full text not readStored summary read	N32 · Actual readingWere preserved archived summaries distinguished from historical full-text access?Required (selected B5 monotherapy comparison for FSS in nonspecific persistent fatigue)	The complete preserved archived summary for 3101 was actually read in this review. NIH inherited extraction, partial PMC access followed by a CAPTCHA, author uploads, visual PDF inspection, full-text access to reviews/registrations, and search indexes are reports from the manuscript at that time. No external materials were attempted or read in this review. S06 S201 S202 S203 S204 S205 S206 S207 S208 S209 S210 S211 S212 S213 S214 S215 S216 S217	No report-specific access-date field exists, so it was left empty and distinguished from the original review date of 2026-09-15.	Identity, current locations/values/SHA read, and historical access/dates for each material	When material acquisition is separately authorized, record access levels, dates, original bytes, and locations read for each report.
33	Met	Full text not readStored summary read	N33 · Absence gateDoes no_human_study mean that all human studies are absent?Required (selected B5 monotherapy comparison for FSS in nonspecific persistent fatigue)	axes.no_human_study=true and human_study_exists=false apply to the fixed direct single-ingredient FSS comparison. related_human_studies_exist=true and search_exhaustive=false are also explicitly stated in the original text. S201 S202 S204 S205 S207	Do not delete related human studies of combination products/specific diseases or interpret the record as a worldwide absence of human evidence.	Original flags, scope, directly eligible/related human-study existence, and search limitations	When updating, review the link between direct eligibility, search scope, and code meaning, and distinguish raw values from the current explanation.
34	Met	Full text not readStored summary read	N34 · Preservation of the original judgmentWhat do ?, empty values, and the subsequent 5 axes mean?Required (selected B5 monotherapy comparison for FSS in nonspecific persistent fatigue)	The original efficacy grade is ?, the score is empty, and the 7 axes are B/P/empty/empty/empty/empty/empty. The subsequent 5 axes and strength count are unscored, not 0. The document_quality B in the original self-review is also separate.	Condition statuses, report counts, and original document assessments were not turned into new scores or official certification.	Original grade/score, application of each axis, gate rationale, and historical calculation references	In a future, separately authorized update of the criteria, compare and distinguish the original inputs, rules, actual calculations, and valid judgments.
35	Partly verified	Full text not readStored summary read	N35 · Conflicts of interestWhat is known about products, company-affiliated authors, and funding?Required (selected B5 monotherapy comparison for FSS in nonspecific persistent fatigue)	For Ullah, the Esserre product and company-employee authorship are reported; for Brouwers, Numico supply/manufacture and author affiliation are reported. Full funding and patent information are unverified. Lupus-study funding is also unverified, and the full Swisse COI information was not reviewed for an efficacy conclusion. S201 S202 S204 S205 S207 S213	Do not transfer related-product sponsorship information to the independence axis of a single-active-ingredient trial.	Product provision, manufacture, company affiliations, research funding, patents, and disclosed COI	Compare original disclosures, product supply, and funding/employment information by study family, and limit the interpretation of independence.
36	Unverified	Full text not readStored summary read	N36 · Registration and selective reportingWas the target FSS outcome prespecified?Required (selected B5 monotherapy comparison for FSS in nonspecific persistent fatigue)	Preregistration and analysis plans for a direct single-active-ingredient FSS comparison are unverified within the preserved scope. The full related registration and CTG shell are distinct levels of material. S213 S214 S215	Do not establish that selective reporting occurred or that registration was absent from gaps in direct plans.	Eligible single-active-ingredient trial registration, protocol, SAP, reasons for changes, and all results	Compare registration/SAP with the actual FSS version, time points, and analyses, and record the scope of changes and nonreporting.
37	Not applicable	Full text not readStored summary read	N37 · Extension questionsAre optimal dose, persistence, and efficacy in special populations also required?Supplementary (required for separate extension questions)	The selected question in this review is the between-group FSS effect in the fixed population. Optimal dose, persistence after discontinuation, and efficacy in all special populations are separate extension questions and were not adopted as additional requirements.	Gaps in verification of the duration and population needed for the claim remain unverified under the earlier items.	Separate direct dose comparisons, follow-up after discontinuation, and prespecified subgroups/interactions	If an extension question is separately requested, review direct dose/follow-up/interaction designs against their plans and results.
38	Partly verified	Full text not readStored summary read	N38 · Level of harm evidenceHow much is known about diarrhea and discontinuations with the same single-active-ingredient exposure?Supplementary (harm and safety boundaries for the same exposure)	The original preserved NIH description mentions the possibility of diarrhea and gastrointestinal discomfort with high-dose B5. The 10 g/day example is not a toxicity threshold/dosing recommendation, and the adequate intake of 5 mg/day is a nutritional reference value. Harm collection, arm-specific denominators/discontinuations, and causality for a single active ingredient used for this fatigue purpose are unverified. S06	The absence of an established upper limit does not mean unlimited safety. Do not transfer combination-product adverse effects or pantethine bleeding cautions to B5 alone.	Event definitions, collection, exposure, time, denominators, arm-specific discontinuations, and concomitant use/causes	Separately review systematic harm/discontinuation, concomitant-use, and follow-up data for the same single-active-ingredient product and population.
39	Unverified	Full text not readStored summary read	N39 · Long-term use and vulnerable populationsHas safety been verified for long-term high-dose use, special populations, and concomitant use?Supplementary (extension to long-term/vulnerable-population safety)	Safety for long-term high-dose use for this fatigue purpose, pregnancy, lactation, children, and liver/kidney disease is unverified. The statement that no important interactions are known is also not proof of safety for all combinations. S06	Do not turn study doses into personal dosing instructions or calculate incidence rates from general warnings.	Data on long-term exposure, rare events, pregnancy/lactation/children, liver/kidney disease, and concomitant use	Review long-term/vulnerable-population and concomitant-use studies with matching exposure and baseline risk in relation to their separate designs and actual collection methods.
40	Met	Full text not readStored summary read	N40 · Review and updatesWhat can change, as of which date and within which material scope?Required (selected B5 monotherapy comparison for FSS in nonspecific persistent fatigue)	The evidence/original review date is 2026-09-15. This conversion of preserved material into a table is not a new search, external full-text reading, calculation, judgment, or deployment. If new single-active-ingredient trials, composition, fatigue tables, registration/SAP, corrections/retractions, or classification/numerical errors are verified, preserve the prior original text and history at the same ID/URL.	The original document_quality B, grade_revalidated, and single-assistant self-review are original reports, not independent clinical certification in this review.	Original review date, scope actually read in the current review, new evidence/corrections, and preservation of versions/original text	In a separately authorized update event, preserve the identity of new material, the full original text, and before/after values, and review linked conditions again.

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40 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 unexplained/nonspecific persistent fatigue; separate from specific diseases and correction of deficiency
Ingredient, formulation and route: Pantothenic acid (vitamin B5) as the sole active ingredient; exact salt to be verified separately · Oral formulation with a single active ingredient; salt, tablet/capsule, and release type unverified
Dose: Unverified — eligible monotherapy dose and frequency not verified
Comparator: Placebo or usual care on the same background treatment; actual composition and concomitant treatment unverified
Measured outcome: Priority given to the between-group difference in change in FSS; endpoint difference separate; version, scoring method, and time points in an eligible trial unverified
Duration: Unverified — eligible monotherapy treatment duration and assessment time points not verified
Questions outside this scope: Specific diseases/correction of deficiency, B-complex products/pomegranate/multivitamins, other molecules/routes, CIS/Chalder/exercise/metabolomics, diarrhea harms/optimal dose/persistence/all populations, and clinical events are separate. /subclaims=[]

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/safety description
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 a direct FSS 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: 18 bibliographic records ≠ 18 independent trials. The same full text/abstract, potentially overlapping cases/preliminary products, reviews, registration/search/patent/official documents/animal data are distinguished; new 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.
NIH ODS official web document	Unverified (external lookups in this review 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; Health Risks from Excessive Pantothenic Acid; Interactions with Medications

S201 · Ullah et al. Combination of Chemically Characterized Pomegranate Extract and Hydrophilic Vitamins against Prolonged Fatigue

Source

Material type: Bibliography for the original combination-product RCT
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: 58 participants, 29 per arm; FSS improvement reported; contribution of B5 alone and FSS analysis denominator 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: 18 bibliographic records ≠ 18 independent trials. The same full text/abstract, potentially overlapping cases/preliminary products, reviews, registration/search/patent/official documents/animal data are distinguished; new 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 (external lookups in this review 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_partial_retrieval_then_captcha. 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: Methods, Sections 2.1 and 2.2; abstract; full text initially read, later detailed retrieval blocked

S202 · Ullah et al. PubMed record and abstract for the same randomized trial

Source

Material type: PubMed bibliography/abstract for the same RCT
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: Same DOI/PMID as S201; product/company-affiliated authors; not an independent 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: 18 bibliographic records ≠ 18 independent trials. The same full text/abstract, potentially overlapping cases/preliminary products, reviews, registration/search/patent/official documents/animal data are distinguished; new 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 (external lookups in this review 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; conflict-of-interest statement; metadata; reference 5

S203 · Esposito et al. Chemical Characterization and Preliminary Evaluation of a Pomegranate Extract, B Vitamins and Vitamin C Supplement

Source

Material type: Product-characterization/preliminary-evaluation 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: S202 reference 5; original-text details/cohort 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: 18 bibliographic records ≠ 18 independent trials. The same full text/abstract, potentially overlapping cases/preliminary products, reviews, registration/search/patent/official documents/animal data are distinguished; new 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 (external lookups in this review 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_and_citing_reference_full_text_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-index metadata; cited reference 5 of S202

S204 · Brouwers et al. The effect of a polynutrient supplement on fatigue and physical activity of patients with chronic fatigue syndrome

Source

Material type: PubMed bibliography/abstract for the CFS combination product
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: Related report of nonsignificant CIS findings; not a direct single-active-ingredient FSS 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: 18 bibliographic records ≠ 18 independent trials. The same full text/abstract, potentially overlapping cases/preliminary products, reviews, registration/search/patent/official documents/animal data are distinguished; new 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 (external lookups in this review 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 and bibliographic metadata

S205 · Brouwers et al. Author-uploaded primary paper, QJM 95:677–683

Source

Material type: Bibliography for the author upload of the same CFS combination-product study
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: 53 participants, 27/26; 48 completed; no detected CIS difference; not an additional independent 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: 18 bibliographic records ≠ 18 independent trials. The same full text/abstract, potentially overlapping cases/preliminary products, reviews, registration/search/patent/official documents/animal data are distinguished; new 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.
Author-shared full-text page	Unverified (external lookups in this review 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_author_upload. 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: Methods pp.678–679; Results pp.680–681; Tables 1–4

S206 · Leung. Systemic lupus erythematosus: a combined deficiency disease. Medical Hypotheses 62:922–924

Source

Material type: Bibliography for the 2004 lupus case report
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: Overlap with the 2007 cases unknown; historical metadata and failed full-text access
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: 18 bibliographic records ≠ 18 independent trials. The same full text/abstract, potentially overlapping cases/preliminary products, reviews, registration/search/patent/official documents/animal data are distinguished; new 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 (external lookups in this review 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_full_text_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: Indexed metadata and DOI; PubMed page CAPTCHA; publisher access failed

S207 · Leung. Systemic Lupus Erythematosus: A Combined Deficiency Disease. Journal of Orthomolecular Medicine 22(4)

Source

Material type: Bibliography for the 2007 lupus multiple-vitamin cases
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: 12 women; calcium pantothenate 10 g/day/concomitant vitamins; control/FSS absent or 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: 18 bibliographic records ≠ 18 independent trials. The same full text/abstract, potentially overlapping cases/preliminary products, reviews, registration/search/patent/official documents/animal data are distinguished; new 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 PDF link	Unverified (external lookups in this review 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_pdf_and_visual_page. 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: Clinical observations, printed p.213, PDF page index 11; observed visually

S208 · De Carvalho and Martinez. Pantothenic acid (vitamin B5) supplementation in rheumatological diseases: A systematic reviews

Source

Material type: Bibliography for the 2025 rheumatology-related review
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: Leung entry/included studies; no duplicate counting alongside original studies
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: 18 bibliographic records ≠ 18 independent trials. The same full text/abstract, potentially overlapping cases/preliminary products, reviews, registration/search/patent/official documents/animal data are distinguished; new 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 review full-text page	Unverified (external lookups in this review 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: review_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: Eligibility criteria; Table I; Leung entry; references

S209 · De Carvalho and Martinez. Pantothenic acid and rheumatological disease review

Source

Material type: Bibliography for a rheumatology review with a different DOI
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: Study summary/references; not an independent single-active-ingredient FSS 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: 18 bibliographic records ≠ 18 independent trials. The same full text/abstract, potentially overlapping cases/preliminary products, reviews, registration/search/patent/official documents/animal data are distinguished; new 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 review full-text page	Unverified (external lookups in this review 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: review_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: Study summary and references

S210 · Nakagawasai et al. Effect of Calcium Pantothenate on Physical Fatigue and Cognitive Dysfunction in Mice

Source

Material type: Metadata/abstract for the original mouse report
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: physical fatigue/cognitive dysfunction; not attributed to human FSS
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: 18 bibliographic records ≠ 18 independent trials. The same full text/abstract, potentially overlapping cases/preliminary products, reviews, registration/search/patent/official documents/animal data are distinguished; new 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 scholarly-index page	Unverified (external lookups in this review 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: primary_metadata_and_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: CiNii abstract linked to J-STAGE original

S211 · Yoshitoshi et al. Pantothenic-acid-deficiency case report

Source

Material type: Bibliography for the B5-deficiency case-report abstract
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: Correction of a specific deficiency; separate from nonspecific persistent fatigue
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: 18 bibliographic records ≠ 18 independent trials. The same full text/abstract, potentially overlapping cases/preliminary products, reviews, registration/search/patent/official documents/animal data are distinguished; new 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.
Journal abstract page	Unverified (external lookups in this review 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: primary_abstract_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: J-STAGE abstract, 16(6):564–571

S212 · Early sports-vitamin supplementation study

Source

Material type: Older sports-vitamin 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: Exercise material; single-active-ingredient FSS details/eligibility 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: 18 bibliographic records ≠ 18 independent trials. The same full text/abstract, potentially overlapping cases/preliminary products, reviews, registration/search/patent/official documents/animal data are distinguished; new 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 (external lookups in this review 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_and_abstract_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: Indexed abstract; associated publisher abstract

S213 · ANZCTR. Understanding the behavioural effects of multivitamin supplements: The BEMS study in women

Source

Material type: Bibliography for the multicomponent BEMS registration
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: Healthy women aged 50~75/secondary Chalder outcome; actual allocation/results 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: 18 bibliographic records ≠ 18 independent trials. The same full text/abstract, potentially overlapping cases/preliminary products, reviews, registration/search/patent/official documents/animal data are distinguished; new 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.
ANZCTR registration page	Unverified (external lookups in this review 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: registry_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: Registration number; intervention; eligibility; outcome hierarchy; allocation methods

S214 · ClinicalTrials.gov. NCT02804828, mitochondrial cocktail/Gulf War illness lead

Source

Material type: Gulf War illness cocktail registration 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: Search lead/JS shell at the time; not verification of a single-active-ingredient FSS plan
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: 18 bibliographic records ≠ 18 independent trials. The same full text/abstract, potentially overlapping cases/preliminary products, reviews, registration/search/patent/official documents/animal data are distinguished; new 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 registration page	Unverified (external lookups in this review 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: search_index_then_registry_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: Search-index intervention lead; direct page JavaScript shell

S215 · ClinicalTrials.gov. NCT07271316, Alii supplement study lead

Source

Material type: Alii mixed-product registration 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: Search lead/JS shell at the time; actual results 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: 18 bibliographic records ≠ 18 independent trials. The same full text/abstract, potentially overlapping cases/preliminary products, reviews, registration/search/patent/official documents/animal data are distinguished; new 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 registration page	Unverified (external lookups in this review 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: search_index_then_registry_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: Search-index mixed-product lead; direct page JavaScript shell

S216 · ME/CFS metabolomics report

Source

Material type: ME/CFS metabolomics 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 search index/CAPTCHA; must not be reversed into an FSS intervention effect
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: 18 bibliographic records ≠ 18 independent trials. The same full text/abstract, potentially overlapping cases/preliminary products, reviews, registration/search/patent/official documents/animal data are distinguished; new 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 (external lookups in this review 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: search_index_then_captcha. 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-index metabolomics description only

S217 · US5304574A patent

Source

Material type: US5304574A patent search 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: Patent examples; independent clinical results/sample 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: 18 bibliographic records ≠ 18 independent trials. The same full text/abstract, potentially overlapping cases/preliminary products, reviews, registration/search/patent/official documents/animal data are distinguished; new 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.
Patent web page	Unverified (external lookups in this review 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: patent_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: Patent examples

Report counts versus independent study counts

This list links materials that may overlap. The seven groups do not mean seven independent clinical trials. S201, S202: F01: excluded from direct scoring; directly eligible=False / S204, S205: F03: excluded from direct scoring; directly eligible=False / S206, S207: F04: excluded from direct scoring; directly eligible=False / S213: F05: excluded from direct scoring; directly eligible=False / S203: related-product preliminary evaluation; exact cohort linkage with S201/202 unverified/independent summations performed: 0 / S208, S209, S206, S207: rheumatology reviews/repeat citations of original lupus cases/overlap between 2004 and 2007 unknown/independent summations performed: 0 / S06, S210, S211, S212, S214, S215, S216, S217: official nutrition, nonhuman/deficiency/exercise/registry-shell/metabolomics/patent leads; not counted as direct single-active-ingredient FSS replications. S201 and S202 are the same Ullah combination-product trial, and S204 and S205 are the same Brouwers CFS combination-product trial. The cohort linkage of the S203 preliminary evaluation and overlap between the S206/S207 lupus cases are unverified. Report counts are not summed as independent trial counts or total participant counts.

Review criteria

Version NGM-v3101-SOLE-B5-NONSPECIFIC-PERSISTENT-FATIGUE-FSS-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 fatigue, intervention, and FSS comparison?

Required materials and conditions: Adults with nonspecific persistent fatigue, oral B5 as the sole active ingredient, comparator on the same background treatment, and between-group FSS results
Conditions for verification: Link the current original effect wording and inclusion/exclusion questions to exact locations.
Requirement and applicability: Required (selected B5 monotherapy comparison for FSS in nonspecific persistent fatigue)
Application exceptions: ME/CFS, lupus, correction of confirmed deficiency, treatment-related fatigue, and multicomponent products are separate.
Why this condition is needed: Needed to avoid combining all vitality claims for the ingredient or fatigue in different diseases 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 tests are internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed

N02 · How was the population with unexplained persistent fatigue defined?

Required materials and conditions: Diagnosis, exclusion tests, age, underlying diseases, and selection criteria
Conditions for verification: Distinguish actual diagnostic/exclusion criteria in the directly eligible population from what remains unverified.
Requirement and applicability: Required (selected B5 monotherapy comparison for FSS in nonspecific persistent fatigue)
Application exceptions: Do not fill an unverified value with an assertion that there was no underlying disease.
Why this condition is needed: Needed to avoid transferring CFS or lupus data merely because the same word, fatigue, is used.
Referenced methods: M03 §3.2.1; detailed population conditions are internally designed

N03 · Are fatigue duration and baseline severity known?

Required materials and conditions: Fatigue-duration threshold, baseline FSS, and distribution by severity
Conditions for verification: Indicate whether actual duration and the baseline scale were verified in an eligible monotherapy trial.
Requirement and applicability: Required (selected B5 monotherapy comparison for FSS in nonspecific persistent fatigue)
Application exceptions: Do not transfer disease diagnostic criteria or baseline scores from another trial.
Why this condition is needed: Needed to avoid using the label persistent fatigue as verified duration or severity values.
Referenced methods: M03 §3.2.1; detailed population conditions are internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed

N04 · Were B5 monotherapy and other molecules or multicomponent products distinguished?

Required materials and conditions: Documentation of pantothenic acid, the exact salt, other active ingredients, and route
Conditions for verification: Link differences in chemical form, combination, and route in the original text with limits on direct attribution.
Requirement and applicability: Required (selected B5 monotherapy comparison for FSS in nonspecific persistent fatigue)
Application exceptions: Verify the salt identity of calcium pantothenate separately and do not import a conversion from another product.
Why this condition is needed: Needed to avoid converting effects of pantethine or multiple ingredients into effects of B5 alone.
Referenced methods: Question-clarification principles in M03 §3.1, §3.2.1–3.2.4; detailed separation rules are internally designed; M03 §3.2.2–3.2.3; reverse-direction labeling and adaptation to tests are internally designed; M03 §3.2.3, M08 §8.2.2–8.2.3; internal application

N05 · Are the origin, quality, and formulation of an eligible single-active-ingredient product known?

Required materials and conditions: Exact salt, origin, purity, batch, brand, release type, and excipients
Conditions for verification: Preserve verified values for a directly eligible formulation and unresolved fields separately.
Requirement and applicability: Required (selected B5 monotherapy comparison for FSS in nonspecific persistent fatigue)
Application exceptions: Specifying a single-active-ingredient oral product in the question differs from actual product specifications.
Why this condition is needed: Needed to avoid substituting specifications of a multicomponent product with a different brand for monotherapy specifications.
Referenced methods: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptation to tests are internally designed

N06 · What are the directly eligible B5 dose and actual total exposure?

Required materials and conditions: Single-active-ingredient product dose, frequency, salt mass, dietary/concurrent supplementation, and actual intake
Conditions for verification: Distinguish unverified eligible dose/frequency from related-study and nutritional values.
Requirement and applicability: Required (selected B5 monotherapy comparison for FSS in nonspecific persistent fatigue)
Application exceptions: Perform no new conversion of calcium pantothenate mass, and do not turn nutritional reference values into treatment doses.
Why this condition is needed: Needed to avoid using the high dose in a lupus combination regimen as a fatigue-treatment dose.
Referenced methods: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptation to 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

N07 · Have eligible treatment duration and FSS assessment time points been specified?

Required materials and conditions: Treatment duration, planned endpoint time points, follow-up, and discontinuation time points
Conditions for verification: Separate unverified eligible treatment duration/assessment time points from the time points in related reports.
Requirement and applicability: Required (selected B5 monotherapy comparison for FSS in nonspecific persistent fatigue)
Application exceptions: Do not arbitrarily specify a universal minimum duration.
Why this condition is needed: Needed to avoid transferring the 28-day, 56-day, and follow-up visits for a multicomponent product to a monotherapy duration.
Referenced methods: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptation to 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; M03 §3.2.1–3.2.4; details of dose, duration, and effect modification are internally designed

N08 · Are placebo or usual care and common treatment actually the same?

Required materials and conditions: Placebo composition, background treatment, rescue medication, and arm-specific changes
Conditions for verification: Distinguish the comparator specified in the question from actual common treatment/changes in an eligible trial.
Requirement and applicability: Required (selected B5 monotherapy comparison for FSS in nonspecific persistent fatigue)
Application exceptions: Do not require all changes in both arms to be identical; record the actual effect of interest.
Why this condition is needed: Needed to avoid attributing effects of different background treatments to an additional B5 effect.
Referenced methods: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptation to 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 · Can diet, deficiency, and concurrent supplementation be distinguished?

Required materials and conditions: Baseline nutrition, B5-deficiency testing, diet, and concurrent active ingredients
Conditions for verification: Link differences between the selected population's baseline status and disease/deficiency cases.
Requirement and applicability: Required (selected B5 monotherapy comparison for FSS in nonspecific persistent fatigue)
Application exceptions: Do not establish that participants are nondeficient if deficiency information is unavailable.
Why this condition is needed: Needed to avoid mixing correction of deficiency with additional supplementation for nonspecific fatigue.
Referenced methods: M03 §3.2.1; detailed population conditions are internally designed; M03 §3.2.2–3.2.3; reverse-direction labeling and adaptation to tests are internally designed; M03 §3.2.3, M08 §8.2.2–8.2.3; internal application

N10 · Have the actual FSS version, range, and scoring method been verified?

Required materials and conditions: Actual FSS version, items/range, aggregation, direction, and measurement procedures
Conditions for verification: Distinguish the scale prioritized in the question from the actual scale in an eligible monotherapy trial.
Requirement and applicability: Required (selected B5 monotherapy comparison for FSS in nonspecific persistent fatigue)
Application exceptions: Do not convert CIS, Chalder, vitality, or mood into FSS.
Why this condition is needed: Needed to avoid mistaking the selection of FSS as the prioritized scale for verification of its actual use.
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

N11 · Are FSS, CIS, Chalder, and mechanisms the same outcome?

Required materials and conditions: Scale, primary/secondary endpoint, time point, population, and intervention for each material
Conditions for verification: Attribute each result's population, scale, and time point to its original location.
Requirement and applicability: Required (selected B5 monotherapy comparison for FSS in nonspecific persistent fatigue)
Application exceptions: Do not delete results on other scales; retain them under their respective questions.
Why this condition is needed: Needed to avoid using different symptom scales or physiological markers as the same direct effect.
Referenced methods: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed; M04 §4.6.3, M15 §15.3.1–15.3.3; status distinctions are internally designed; M08 Table 8.2.a, M03 §3.2.4; internal application; M03 §3.2.4; internally specified boundary on extensions

N12 · Were between-group differences in change distinguished from endpoint differences and within-group differences?

Required materials and conditions: Baseline, change, and endpoint values, definition of between-group comparison, and adjustment/analysis methods
Conditions for verification: Indicate the between-group/within-group and change/endpoint definitions of the actual selected results and the gaps.
Requirement and applicability: Required (selected B5 monotherapy comparison for FSS in nonspecific persistent fatigue)
Application exceptions: Do not fill in an analysis not specified in the original text as ITT or an adjusted effect.
Why this condition is needed: Needed to avoid turning within-group improvement into an effect superior to placebo.
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

N13 · Are the directly relevant FSS effect, CI, and P value known?

Required materials and conditions: Eligible between-group effect, uncertainty interval, P value, and units
Conditions for verification: Distinguish empty values in primary_effect from the direction of related reports.
Requirement and applicability: Required (selected B5 monotherapy comparison for FSS in nonspecific persistent fatigue)
Application exceptions: Do not turn an unverified result into an effect of 0, nonsignificance, or equivalence.
Why this condition is needed: Needed to avoid filling in an effect based on significance or the number of related studies.
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

N14 · How many participants were allocated, analyzed, and completed, respectively?

Required materials and conditions: Arm-specific allocation, analysis, completion, and missing-data/dropout handling in an eligible monotherapy trial
Conditions for verification: Distinguish eligible outcome-specific denominators from what remains unverified.
Requirement and applicability: Required (selected B5 monotherapy comparison for FSS in nonspecific persistent fatigue)
Application exceptions: Do not transfer Ullah 58 or Brouwers 53/48 as monotherapy denominators.
Why this condition is needed: Needed to avoid using another trial's total sample size as the directly relevant FSS analysis denominator.
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

N15 · Are allocation, concealment, and assessment procedures in the direct comparison known?

Required materials and conditions: Actual design, allocation/concealment, baseline balance, and assessor/participant blinding
Conditions for verification: Link actual design/measurement information for the direct results with the missing material.
Requirement and applicability: Required (selected B5 monotherapy comparison for FSS in nonspecific persistent fatigue)
Application exceptions: Do not arbitrarily mark crossover or cluster designs as not applicable when the design is unverified.
Why this condition is needed: Needed to avoid using a related RCT label as a bias assessment of an eligible monotherapy trial.
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

N16 · Were the effects of ITT/PP, adherence, rescue treatment, and missing data verified?

Required materials and conditions: Effect of interest, analysis population, adherence, arm-specific changes, and missing-data handling
Conditions for verification: Indicate the directly eligible analysis and why verification is not possible.
Requirement and applicability: Required (selected B5 monotherapy comparison for FSS in nonspecific persistent fatigue)
Application exceptions: Do not arbitrarily assume ITT if the analysis method is unavailable.
Why this condition is needed: Needed to avoid mixing the effect of assignment with effects among adherent participants or before-and-after results among completers.
Referenced methods: M03 §3.2.3, M08 §8.2.2–8.2.3; internal application; M08 §8.2.2, M15 §15.3.1; internal application; M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptations are internally designed

N17 · What magnitude of fatigue difference does the interval allow?

Required materials and conditions: Direct effect/CI, endpoint-specific variance, and the basis for an MCID
Conditions for verification: Explain the reported interval and importance criterion, or why interpretation is not possible.
Requirement and applicability: Required (selected B5 monotherapy comparison for FSS in nonspecific persistent fatigue)
Application exceptions: Do not arbitrarily adopt an MCID, minimum sample size, or common duration.
Why this condition is needed: Needed to avoid declaring sufficiency based only on sample size, statistical significance, or the number of reports.
Referenced methods: M15 §15.3.1–15.3.3; internal 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

N18 · What produced the FSS improvement in Ullah?

Required materials and conditions: Product composition, endpoints, time points, and arm-specific results in the 58-participant trial
Conditions for verification: Link the positive results with the actual combination product and denominator limitations.
Requirement and applicability: Required (selected B5 monotherapy comparison for FSS in nonspecific persistent fatigue)
Application exceptions: Do not isolate a contribution from B5 solely because it was included.
Why this condition is needed: Needed to limit attribution to a single ingredient while preserving favorable related 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; 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; M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses is this project's own design; M03 §3.2.3, M08 §8.2.2–8.2.3; internal application

N19 · Are the Ullah full text, abstract, and preliminary evaluation independent replications?

Required materials and conditions: S201/S202/S203 report identities, DOI/PMID, and cohort linkage
Conditions for verification: Distinguish the explicit identity of reports of the same trial from the unresolved relationship with the preliminary evaluation.
Requirement and applicability: Required (selected B5 monotherapy comparison for FSS in nonspecific persistent fatigue)
Application exceptions: Do not establish cohort linkage for the preliminary evaluation solely from similar names.
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 internal 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; internal application

N20 · Does nonsignificance in Brouwers mean that B5 alone is ineffective?

Required materials and conditions: CIS, design, between-group results, and original tables for the CFS combination product
Conditions for verification: Link the differences in population, combination product, and CIS with the scope of the nonsignificant findings.
Requirement and applicability: Required (selected B5 monotherapy comparison for FSS in nonspecific persistent fatigue)
Application exceptions: Do not turn nonsignificance into equivalence or ineffectiveness for all fatigue.
Why this condition is needed: Needed to preserve unfavorable related findings as well and avoid converting them into an effect of 0 for a different question.
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; M04 §4.6.1–4.6.2, M15 §15.3.1; internal application

N21 · What denominators do 53 allocated and 48 completed represent?

Required materials and conditions: Brouwers arm-specific allocation, completion, outcome-specific analyses, and handling of dropouts
Conditions for verification: Attribute the original 53 (27/26) allocated and 48 completed to the corresponding combination-product trial.
Requirement and applicability: Required (selected B5 monotherapy comparison for FSS in nonspecific persistent fatigue)
Application exceptions: Do not calculate new dropout counts or arm-specific rates from the difference.
Why this condition is needed: Needed to avoid merging allocation/completion counts from a related trial into 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; internal application

N22 · Is the improvement in 12 people with lupus a single-ingredient comparison?

Required materials and conditions: Case populations, concomitant prescriptions, comparator, and validated fatigue scale
Conditions for verification: Link the original 12 participants, 10 g/day, and concomitant vitamins with the reasons for direct exclusion.
Requirement and applicability: Required (selected B5 monotherapy comparison for FSS in nonspecific persistent fatigue)
Application exceptions: Do not convert calcium-salt mass or transfer a disease-specific sample to the target population.
Why this condition is needed: Needed to avoid turning an uncontrolled multiple-vitamin narrative into a between-group result for a single ingredient.
Referenced methods: M03 §3.2.1; detailed population conditions are 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; M08 §8.1–8.2.3; internal application; M03 §3.2.3, M08 §8.2.2–8.2.3; internal application; design considerations in M19 §19.2.2–19.2.4; detailed confounding records are this project's own design

N23 · Do the cases in the 2004 and 2007 lupus reports overlap?

Required materials and conditions: Populations, recruitment, case numbers, periods, and linkage in the two reports
Conditions for verification: Preserve the original uncertainty about overlap and the principle of not summing the samples.
Requirement and applicability: Required (selected B5 monotherapy comparison for FSS in nonspecific persistent fatigue)
Application exceptions: Do not establish that cases differ solely from publication years.
Why this condition is needed: Needed to avoid counting repeat reports of the same cases as independent replications and additional participants.
Referenced methods: Distinction between studies and reports in M04 §4.6.1–4.6.2; cohort/outcome linkage is an internal application; M04 §4.6.1–4.6.2, M15 §15.3.1; internal application; M04 §4.6.1–4.6.2; adaptation for harm data is this project's own design

N24 · Are the rheumatology reviews separate direct trials?

Required materials and conditions: Original reports included in S208/S209, linkage to Leung, and overlap
Conditions for verification: Distinguish the bibliographic records and historical locations of the two reviews from direct material from original trials.
Requirement and applicability: Required (selected B5 monotherapy comparison for FSS in nonspecific persistent fatigue)
Application exceptions: An indication of historical full-text access to a review is not direct reading in this review.
Why this condition is needed: Needed to avoid double-counting reviews and their included cases as unique trials.
Referenced methods: Distinction between studies and reports in M04 §4.6.1–4.6.2; cohort/outcome linkage is an internal 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; internal application

N25 · Is Chalder in BEMS a direct FSS result?

Required materials and conditions: ACTRN registration, healthy women aged 50~75, multicomponent composition, and endpoint hierarchy/results
Conditions for verification: Link the population, combination intervention, secondary endpoint, and unverified actual results.
Requirement and applicability: Required (selected B5 monotherapy comparison for FSS in nonspecific persistent fatigue)
Application exceptions: Distinguish the planned registered sample from actual allocated/analyzed counts.
Why this condition is needed: Needed to avoid elevating the existence of a registration to a target single-ingredient FSS result.
Referenced methods: M03 §3.2.1; detailed population conditions are 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; 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 Table 8.2.a, M04 §4.6.3; internal application

N26 · Does a CTG shell mean that results are absent?

Required materials and conditions: Actual text, interventions/endpoints, and results of NCT02804828 and NCT07271316
Conditions for verification: Distinguish historical search leads and shells from unverified plans/results.
Requirement and applicability: Required (selected B5 monotherapy comparison for FSS in nonspecific persistent fatigue)
Application exceptions: No current access was attempted, and historical shells are not treated as failures in this review.
Why this condition is needed: Needed to avoid turning access failures or shell pages into negative trials or 0 studies worldwide.
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; internal application

N27 · Do mouse fatigue and CoA functions constitute an FSS effect in adults?

Required materials and conditions: Species, experimental intervention, physiological/behavioral endpoints, and limits of human applicability
Conditions for verification: Identify nonhuman/mechanistic materials at a separate level, with their original bibliographic locations.
Requirement and applicability: Required (selected B5 monotherapy comparison for FSS in nonspecific persistent fatigue)
Application exceptions: Traditional uses or metabolic functions are not eligible between-group effect estimates.
Why this condition is needed: Needed to avoid substituting mechanisms or animal responses for direct human treatment effects.
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; this project's own boundary on extensions

N28 · Can B5 deficiency case reports be used for the same fatigue treatment?

Required materials and conditions: Deficiency diagnosis, correction, population, and assessment endpoints
Conditions for verification: Indicate the bibliographic/access level of deficiency cases and the boundaries for direct exclusion.
Requirement and applicability: Required (selected B5 monotherapy comparison for FSS in nonspecific persistent fatigue)
Application exceptions: Do not reclassify the material as a comparative FSS trial in adults when original details are absent.
Why this condition is needed: Needed to distinguish correction of a specific deficiency from additional supplementation for nonspecific persistent fatigue.
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; 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 the older sports-vitamin material answer the FSS question?

Required materials and conditions: Product composition, populations, exercise/fatigue endpoints, and actual analyses
Conditions for verification: Link the verified level of material with the reasons for not attributing it directly.
Requirement and applicability: Required (selected B5 monotherapy comparison for FSS in nonspecific persistent fatigue)
Application exceptions: Do not establish single-ingredient intervention/scale eligibility from bibliographic records or search abstracts.
Why this condition is needed: Needed to avoid substituting exercise performance or vitality wording for FSS in persistent fatigue.
Referenced methods: M03 §3.2.1; detailed population conditions are 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; M03 §3.2.4; this project's own boundary on extensions

N30 · Do ME/CFS metabolomic data represent a single-ingredient treatment effect?

Required materials and conditions: Direction of exposure, disease, metabolomic findings, and whether a direct intervention exists
Conditions for verification: Indicate the disease/endpoint level of the search leads and the lack of direct attribution.
Requirement and applicability: Required (selected B5 monotherapy comparison for FSS in nonspecific persistent fatigue)
Application exceptions: Do not extrapolate metabolomic differences to doses or individual treatment responses.
Why this condition is needed: Needed to avoid reversing associations or surrogate markers into an effect of administering the ingredient.
Referenced methods: M03 §3.2.1; detailed population conditions are 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; 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; this project's own boundary on extensions

N31 · Do patent examples constitute clinical comparative evidence?

Required materials and conditions: Populations, experiments, and independent clinical results in the US5304574A examples
Conditions for verification: Link the verified patent search-index level to its original location.
Requirement and applicability: Required (selected B5 monotherapy comparison for FSS in nonspecific persistent fatigue)
Application exceptions: Do not label patent rights/cases as independent replications of efficacy.
Why this condition is needed: Needed to avoid confusing the existence of a patent with eligible trials or demonstrated efficacy.
Referenced methods: Distinction between studies and reports in M04 §4.6.1–4.6.2; cohort/outcome linkage is an internal 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; Chamgap's own conditions for independence and attribution. The official methods sections used in this pilot do not guarantee all of these detailed items; M04 §4.6.1–4.6.2, M15 §15.3.1; internal application

N32 · Were preserved archived summaries distinguished from historical full-text access?

Required materials and conditions: Identity, current locations/values/SHA read, and historical access/dates for each material
Conditions for verification: Indicate the summaries actually read in the current review separately from external materials not attempted/not read, and connect the links.
Requirement and applicability: Required (selected B5 monotherapy comparison for FSS in nonspecific persistent fatigue)
Application exceptions: Historical CAPTCHAs, shells, and unacquired material are not current access failures, and access dates are not inferred.
Why this condition is needed: Needed to avoid turning a URL or historical access 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

N33 · Does no_human_study mean that all human studies are absent?

Required materials and conditions: Original flags, scope, directly eligible/related human-study existence, and search limitations
Conditions for verification: Preserve the original flags together with their semantic limitations and the existence of related human studies.
Requirement and applicability: Required (selected B5 monotherapy comparison for FSS in nonspecific persistent fatigue)
Application exceptions: Do not alter the original true/false/empty values to make them identical.
Why this condition is needed: Needed to avoid reading a code flag as 0 studies worldwide or no effect.
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; internal application

N34 · What do ?, empty values, and the subsequent 5 axes mean?

Required materials and conditions: Original grade/score, application of each axis, gate rationale, and historical calculation references
Conditions for verification: Preserve the applied/unscored meaning of the original B/P/5 null axes, ?, and empty score.
Requirement and applicability: Required (selected B5 monotherapy comparison for FSS in nonspecific persistent fatigue)
Application exceptions: Do not merge document quality B with efficacy ?, or rerun the original calculator.
Why this condition is needed: Needed to avoid elevating new verification statuses into efficacy grades or scores.
Referenced methods: M04 §4.5, §4.6.3; limitations of the current material conversion follow the user's scope and this project's own design; M15 §15.3.1–15.3.3; internal application

N35 · What is known about products, company-affiliated authors, and funding?

Required materials and conditions: Product provision, manufacture, company affiliations, research funding, patents, and disclosed COI
Conditions for verification: Distinguish the reported Esserre, Numico, and Swisse information from what remains unverified.
Requirement and applicability: Required (selected B5 monotherapy comparison for FSS in nonspecific persistent fatigue)
Application exceptions: Do not delete results because conflicts of interest exist or treat their absence as absence of bias.
Why this condition is needed: Needed to avoid turning partial company information or unverified information into independent funding/independent replication.
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; M08 §8.1–8.2.3; internal application

N36 · Was the target FSS outcome prespecified?

Required materials and conditions: Eligible single-active-ingredient trial registration, protocol, SAP, reasons for changes, and all results
Conditions for verification: Link the plans compared and the scope of direct material not compared to their locations.
Requirement and applicability: Required (selected B5 monotherapy comparison for FSS in nonspecific persistent fatigue)
Application exceptions: The related BEMS registration is a plan for a different population, product, and scale.
Why this condition is needed: Needed to avoid turning the failure to acquire direct plans into confirmation of nonregistration or selective reporting.
Referenced methods: M08 Table 8.2.a, M04 §4.6.3; internal application; data collection/selection principles in M04 §4.5–4.6; separation of access from reading and the hyperlink contract are internally designed; M04 §4.5, §4.6.3; the limits of the current material conversion follow the user's scope and the project's own design

N37 · Are optimal dose, persistence, and efficacy in special populations also required?

Required materials and conditions: Separate direct dose comparisons, follow-up after discontinuation, and prespecified subgroups/interactions
Conditions for verification: Record separately the nonapplicability boundary for extensions of efficacy beyond the direct question and what remains unverified.
Requirement and applicability: Supplementary (required for separate extension questions)
Application exceptions: The actual duration relevant to the assessed claim must be verified, but optimal-dose/all-subgroup trials are not imposed as additional requirements.
Why this condition is needed: Needed to avoid extending the narrow FSS question to all long-term and optimal-dose claims.
Referenced methods: M03 §3.2.1–3.2.4; details of dose, persistence, and effect modification are internally designed; M03 §3.2.4; internally specified boundary on extensions; question-clarification principles in M03 §3.1, §3.2.1–3.2.4; detailed separation rules are internally designed

N38 · How much is known about diarrhea and discontinuations with the same single-active-ingredient exposure?

Required materials and conditions: Event definitions, collection, exposure, time, denominators, arm-specific discontinuations, and concomitant use/causes
Conditions for verification: Distinguish the NIH high-dose GI warning from gaps in denominators/methods for direct target harms.
Requirement and applicability: Supplementary (harm and safety boundaries for the same exposure)
Application exceptions: Do not turn unverified efficacy into safety or copy cautions for combination products/pantethine.
Why this condition is needed: Needed to avoid converting general safety commentary into incidence rates in the target single-active-ingredient trial or overall safety.
Referenced methods: M19 §19.1.2–19.2.4; internal application; M19 §19.1.2–19.2.4; detailed distinctions are internally designed; design-specific harm questions in M19 §19.2; details of temporal relationships are internally designed; M19 §19.2.2–19.2.4, M03 §3.2.3; internal application; design considerations in M19 §19.2.2–19.2.4; detailed confounding records are internally designed; M19 §19.1.2–19.2.4, M04 §4.6.3; internal application; Chamgap's own interpretive boundary. The principles of M19 are referenced; this is not an application of a formal causality tool

N39 · Has safety been verified for long-term high-dose use, special populations, and concomitant use?

Required materials and conditions: Data on long-term exposure, rare events, pregnancy/lactation/children, liver/kidney disease, and concomitant use
Conditions for verification: Preserve the safety limitations for the selected fatigue purpose and the original Caution label.
Requirement and applicability: Supplementary (extension to long-term/vulnerable-population safety)
Application exceptions: Do not establish that unverified interactions are absent.
Why this condition is needed: Needed to avoid using limited general descriptions as proof of safety for all populations/combinations.
Referenced methods: M19 §19.1.2–19.2.4; internal application; Chamgap's own interpretive boundary. The principles of M19 are referenced; this is not an application of a formal causality tool

N40 · What can change, as of which date and within which material scope?

Required materials and conditions: Original review date, scope actually read in the current review, new evidence/corrections, and preservation of versions/original text
Conditions for verification: Distinguish the original date and self-review, what has not been newly performed, and the conditions for updates/the same ID.
Requirement and applicability: Required (selected B5 monotherapy comparison for FSS in nonspecific persistent fatigue)
Application exceptions: The original first_published_at is an editorial reference date, not proof of actual server deployment.
Why this condition is needed: Needed to avoid overstating the current table conversion as a current comprehensive search, publication, or official certification.
Referenced methods: M04 §4.5, §4.6.3; the limits of the current material conversion follow the user's scope and the project's own design; data collection/selection principles in M04 §4.5–4.6; separation of access from reading and the hyperlink contract are internally designed; M04 §4.6.3, M15 §15.3.1–15.3.3; status distinctions are internally designed

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 preserved methodological principles/version from 1585 and actual original-byte copies of 5 HTML files; not new reading of methodological full texts or application of official tools in this review

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 preserved methodological principles/version from 1585 and actual original-byte copies of 5 HTML files; not new reading of methodological full texts or application of official tools in this review

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 preserved methodological principles/version from 1585 and actual original-byte copies of 5 HTML files; not new reading of methodological full texts or application of official tools in this review

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 preserved methodological principles/version from 1585 and actual original-byte copies of 5 HTML files; not new reading of methodological full texts or application of official tools in this review

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 preserved methodological principles/version from 1585 and actual original-byte copies of 5 HTML files; not new reading of methodological full texts or application of official tools in this review

What the statuses mean

Partly verified: Some related material/bibliographic/historical information exists, but gaps remain in direct comparisons, products/denominators/plans, and access/harms
Unverified: The selected direct result or necessary material could not be verified within the preserved scope; this does not mean no effect or 0 studies
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 optimal dose, persistence, all populations/clinical events are not imposed as additional requirements for the original FSS question; this does not substitute for other unverified matters
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/attribution, and linkage conditions; not direct FSS efficacy, original 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 40 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 fatigue, intervention, and FSS comparison?

Current findings: The selected question is whether oral treatment with pantothenic acid as the sole active ingredient lowers FSS more than placebo or usual care on the same background treatment in adults with unexplained/nonspecific persistent fatigue. subclaims is an empty list.
Verification status: Met
Materials actually read: The complete, exactly retained archived summary was actually read; external material and separate earlier original texts were not read in this review
Why unverified: This verifies the identity of the question, not an effect or the absence of all human studies.
Reason for missing information: This verifies the identity of the question, not an effect or the absence of all human studies.
Required materials and conditions: Adults with nonspecific persistent fatigue, oral B5 as the sole active ingredient, comparator on the same background treatment, and between-group FSS results
Materials to obtain first: Adults with nonspecific persistent fatigue, oral B5 as the sole active ingredient, comparator on the same background treatment, and between-group FSS results
Further research: Compare differences in population, intervention, and endpoint between the existing question and candidate results for each material.
Remaining uncertainty: This verifies the identity of the question, not an effect or the absence of all human studies.
Conditions for verification: Link the current original effect wording and inclusion/exclusion questions to exact locations.
Why this condition is needed: Needed to avoid combining all vitality claims for the ingredient or fatigue in different diseases into a single question.
Application exceptions: ME/CFS, lupus, correction of confirmed deficiency, treatment-related fatigue, and multicomponent products are separate.
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 tests are internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed

Related sources S201 S202 S204 S205 S207

N02 · How was the population with unexplained persistent fatigue defined?

Current findings: The population was fixed to adults with unexplained/nonspecific persistent fatigue, but diagnosis, baseline nutrition/deficiency, and exclusion criteria in eligible monotherapy trials were not verified.
Verification status: Unverified
Materials actually read: The complete, exactly retained archived summary was actually read; external material and separate earlier original texts were not read in this review
Why unverified: The population specified in the question does not substitute for actual recruitment criteria in an eligible study.
Reason for missing information: The population specified in the question does not substitute for actual recruitment criteria in an eligible study.
Required materials and conditions: Diagnosis, exclusion tests, age, underlying diseases, and selection criteria
Materials to obtain first: Diagnosis, exclusion tests, age, underlying diseases, and selection criteria
Further research: Obtain recruitment and diagnostic tables for the target population and compare applicability boundaries with groups with other causes.
Remaining uncertainty: The population specified in the question does not substitute for actual recruitment criteria in an eligible study.
Conditions for verification: Distinguish actual diagnostic/exclusion criteria in the directly eligible population from what remains unverified.
Why this condition is needed: Needed to avoid transferring CFS or lupus data merely because the same word, fatigue, is used.
Application exceptions: Do not fill an unverified value with an assertion that there was no underlying disease.
Referenced methods: M03 §3.2.1; detailed population conditions are internally designed

Related sources S201 S205 S207 S213

N03 · Are fatigue duration and baseline severity known?

Current findings: The fatigue-duration criterion and baseline FSS in a directly relevant monotherapy trial are unverified within the preserved scope.
Verification status: Unverified
Materials actually read: The complete, exactly retained archived summary was actually read; external material and separate earlier original texts were not read in this review
Why unverified: Do not fill in the duration for the selected question solely from the prolonged fatigue label in a related product trial.
Reason for missing information: Do not fill in the duration for the selected question solely from the prolonged fatigue label in a related product trial.
Required materials and conditions: Fatigue-duration threshold, baseline FSS, and distribution by severity
Materials to obtain first: Fatigue-duration threshold, baseline FSS, and distribution by severity
Further research: Link recruitment criteria and baseline tables to time points/scale versions to review eligibility.
Remaining uncertainty: Do not fill in the duration for the selected question solely from the prolonged fatigue label in a related product trial.
Conditions for verification: Indicate whether actual duration and the baseline scale were verified in an eligible monotherapy trial.
Why this condition is needed: Needed to avoid using the label persistent fatigue as verified duration or severity values.
Application exceptions: Do not transfer disease diagnostic criteria or baseline scores from another trial.
Referenced methods: M03 §3.2.1; detailed population conditions are internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed

Related sources S201 S202

N04 · Were B5 monotherapy and other molecules or multicomponent products distinguished?

Current findings: The question concerns oral B5 as the sole active ingredient. Pantethine, pantetheine, dexpanthenol/panthenol, B-complex products, multivitamins, and multicomponent energy products were distinguished from the direct intervention. The exact eligible salt is unverified.
Verification status: Met
Materials actually read: The complete, exactly retained archived summary was actually read; external material and separate earlier original texts were not read in this review
Why unverified: This verifies the distinction between boundaries; it does not mean that a specific single-active-ingredient product was acquired.
Reason for missing information: This verifies the distinction between boundaries; it does not mean that a specific single-active-ingredient product was acquired.
Required materials and conditions: Documentation of pantothenic acid, the exact salt, other active ingredients, and route
Materials to obtain first: Documentation of pantothenic acid, the exact salt, other active ingredients, and route
Further research: Compare manufacturing-composition and chemical-form documents for each result to verify sole-active-ingredient status.
Remaining uncertainty: This verifies the distinction between boundaries; it does not mean that a specific single-active-ingredient product was acquired.
Conditions for verification: Link differences in chemical form, combination, and route in the original text with limits on direct attribution.
Why this condition is needed: Needed to avoid converting effects of pantethine or multiple ingredients into effects of B5 alone.
Application exceptions: Verify the salt identity of calcium pantothenate separately and do not import a conversion from another product.
Referenced methods: Question-clarification principles in M03 §3.1, §3.2.1–3.2.4; detailed separation rules are internally designed; M03 §3.2.2–3.2.3; reverse-direction labeling and adaptation to tests are internally designed; M03 §3.2.3, M08 §8.2.2–8.2.3; internal application

Related sources S06 S201 S205 S207 S213

N05 · Are the origin, quality, and formulation of an eligible single-active-ingredient product known?

Current findings: Origin, salt, brand, purity, batch, formulation, and release type are unverified in eligible monotherapy trials.
Verification status: Unverified
Materials actually read: The complete, exactly retained archived summary was actually read; external material and separate earlier original texts were not read in this review
Why unverified: Esserre or Swisse brand information belongs to the respective multicomponent product.
Reason for missing information: Esserre or Swisse brand information belongs to the respective multicomponent product.
Required materials and conditions: Exact salt, origin, purity, batch, brand, release type, and excipients
Materials to obtain first: Exact salt, origin, purity, batch, brand, release type, and excipients
Further research: Verify formulation specifications, active-ingredient analyses, and batch records for the eligible comparison together with the results.
Remaining uncertainty: Esserre or Swisse brand information belongs to the respective multicomponent product.
Conditions for verification: Preserve verified values for a directly eligible formulation and unresolved fields separately.
Why this condition is needed: Needed to avoid substituting specifications of a multicomponent product with a different brand for monotherapy specifications.
Application exceptions: Specifying a single-active-ingredient oral product in the question differs from actual product specifications.
Referenced methods: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptation to tests are internally designed

Related sources S201 S202 S203 S213

N06 · What are the directly eligible B5 dose and actual total exposure?

Current findings: The eligible monotherapy dose and frequency are unverified. Calcium pantothenate 10 g/day in the lupus cases and NIH nutritional reference values do not fill in a directly relevant fatigue-treatment dose.
Verification status: Unverified
Materials actually read: The complete, exactly retained archived summary was actually read; external material and separate earlier original texts were not read in this review
Why unverified: Nominal or actual amounts and salt conversions were not arbitrarily generated.
Reason for missing information: Nominal or actual amounts and salt conversions were not arbitrarily generated.
Required materials and conditions: Single-active-ingredient product dose, frequency, salt mass, dietary/concurrent supplementation, and actual intake
Materials to obtain first: Single-active-ingredient product dose, frequency, salt mass, dietary/concurrent supplementation, and actual intake
Further research: Obtain administration, adherence, and dietary-exposure records from a comparative monotherapy trial to assess actual exposure.
Remaining uncertainty: Nominal or actual amounts and salt conversions were not arbitrarily generated.
Conditions for verification: Distinguish unverified eligible dose/frequency from related-study and nutritional values.
Why this condition is needed: Needed to avoid using the high dose in a lupus combination regimen as a fatigue-treatment dose.
Application exceptions: Perform no new conversion of calcium pantothenate mass, and do not turn nutritional reference values into treatment doses.
Referenced methods: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptation to 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 S06 S207

N07 · Have eligible treatment duration and FSS assessment time points been specified?

Current findings: Eligible monotherapy treatment duration and assessment time points are unverified. Assessments at 28 days and 56 days and follow-up visits for Ullah's multicomponent product were preserved as distinct.
Verification status: Unverified
Materials actually read: The complete, exactly retained archived summary was actually read; external material and separate earlier original texts were not read in this review
Why unverified: A different formulation's schedule does not verify duration for the selected question.
Reason for missing information: A different formulation's schedule does not verify duration for the selected question.
Required materials and conditions: Treatment duration, planned endpoint time points, follow-up, and discontinuation time points
Materials to obtain first: Treatment duration, planned endpoint time points, follow-up, and discontinuation time points
Further research: Collect plans, actual administration duration, and each follow-up result separately and compare them with prespecified endpoints.
Remaining uncertainty: A different formulation's schedule does not verify duration for the selected question.
Conditions for verification: Separate unverified eligible treatment duration/assessment time points from the time points in related reports.
Why this condition is needed: Needed to avoid transferring the 28-day, 56-day, and follow-up visits for a multicomponent product to a monotherapy duration.
Application exceptions: Do not arbitrarily specify a universal minimum duration.
Referenced methods: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptation to 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; M03 §3.2.1–3.2.4; details of dose, duration, and effect modification are internally designed

Related sources S201 S202

N08 · Are placebo or usual care and common treatment actually the same?

Current findings: Placebo or usual care on identical background treatment is the planned comparison. Placebo composition, common treatment, and rescue medication in eligible monotherapy trials are unverified.
Verification status: Unverified
Materials actually read: The complete, exactly retained archived summary was actually read; external material and separate earlier original texts were not read in this review
Why unverified: The presence of a control arm in a multicomponent trial alone does not meet the monotherapy comparison conditions.
Reason for missing information: The presence of a control arm in a multicomponent trial alone does not meet the monotherapy comparison conditions.
Required materials and conditions: Placebo composition, background treatment, rescue medication, and arm-specific changes
Materials to obtain first: Placebo composition, background treatment, rescue medication, and arm-specific changes
Further research: Compare arm-specific prescription, placebo, rescue-treatment, and change records for the eligible comparison against the analysis plan.
Remaining uncertainty: The presence of a control arm in a multicomponent trial alone does not meet the monotherapy comparison conditions.
Conditions for verification: Distinguish the comparator specified in the question from actual common treatment/changes in an eligible trial.
Why this condition is needed: Needed to avoid attributing effects of different background treatments to an additional B5 effect.
Application exceptions: Do not require all changes in both arms to be identical; record the actual effect of interest.
Referenced methods: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptation to 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 S201 S205 S207

N09 · Can diet, deficiency, and concurrent supplementation be distinguished?

Current findings: Baseline nutrition and deficiency status in eligible monotherapy trials are unverified. Deficiency case reports and the nonspecific-fatigue question are separate.
Verification status: Unverified
Materials actually read: The complete, exactly retained archived summary was actually read; external material and separate earlier original texts were not read in this review
Why unverified: Do not fill in baseline information with mechanisms or blood markers.
Reason for missing information: Do not fill in baseline information with mechanisms or blood markers.
Required materials and conditions: Baseline nutrition, B5-deficiency testing, diet, and concurrent active ingredients
Materials to obtain first: Baseline nutrition, B5-deficiency testing, diet, and concurrent active ingredients
Further research: Obtain baseline nutrition, deficiency measurements, and concurrent-supplementation information by arm to review applicability.
Remaining uncertainty: Do not fill in baseline information with mechanisms or blood markers.
Conditions for verification: Link differences between the selected population's baseline status and disease/deficiency cases.
Why this condition is needed: Needed to avoid mixing correction of deficiency with additional supplementation for nonspecific fatigue.
Application exceptions: Do not establish that participants are nondeficient if deficiency information is unavailable.
Referenced methods: M03 §3.2.1; detailed population conditions are internally designed; M03 §3.2.2–3.2.3; reverse-direction labeling and adaptation to tests are internally designed; M03 §3.2.3, M08 §8.2.2–8.2.3; internal application

Related sources S211 S06

N10 · Have the actual FSS version, range, and scoring method been verified?

Current findings: FSS is the prioritized scale for this question. Its actual version, range, and scoring method in an eligible monotherapy trial are unverified.
Verification status: Unverified
Materials actually read: The complete, exactly retained archived summary was actually read; external material and separate earlier original texts were not read in this review
Why unverified: An FSS label does not mean that all measurement conditions have been verified.
Reason for missing information: An FSS label does not mean that all measurement conditions have been verified.
Required materials and conditions: Actual FSS version, items/range, aggregation, direction, and measurement procedures
Materials to obtain first: Actual FSS version, items/range, aggregation, direction, and measurement procedures
Further research: Compare the actual scale version and scoring/collection procedures against results tables and blinding information.
Remaining uncertainty: An FSS label does not mean that all measurement conditions have been verified.
Conditions for verification: Distinguish the scale prioritized in the question from the actual scale in an eligible monotherapy trial.
Why this condition is needed: Needed to avoid mistaking the selection of FSS as the prioritized scale for verification of its actual use.
Application exceptions: Do not convert CIS, Chalder, vitality, or mood into FSS.
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 S201 S202 S205 S213

N11 · Are FSS, CIS, Chalder, and mechanisms the same outcome?

Current findings: FSS for Ullah's multicomponent product, CIS for the CFS multicomponent product, the secondary Chalder endpoint in the healthy-women registration, and animal/metabolic and exercise markers were distinguished.
Verification status: Met
Materials actually read: The complete, exactly retained archived summary was actually read; external material and separate earlier original texts were not read in this review
Why unverified: Improvement in related symptoms or mechanistic observations does not substitute for the FSS effect of B5 alone.
Reason for missing information: Improvement in related symptoms or mechanistic observations does not substitute for the FSS effect of B5 alone.
Required materials and conditions: Scale, primary/secondary endpoint, time point, population, and intervention for each material
Materials to obtain first: Scale, primary/secondary endpoint, time point, population, and intervention for each material
Further research: Compare the original definitions of different scales and planned endpoints, and do not merge them into a common effect.
Remaining uncertainty: Improvement in related symptoms or mechanistic observations does not substitute for the FSS effect of B5 alone.
Conditions for verification: Attribute each result's population, scale, and time point to its original location.
Why this condition is needed: Needed to avoid using different symptom scales or physiological markers as the same direct effect.
Application exceptions: Do not delete results on other scales; retain them under their respective questions.
Referenced methods: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed; M04 §4.6.3, M15 §15.3.1–15.3.3; status distinctions are internally designed; M08 Table 8.2.a, M03 §3.2.4; internal application; M03 §3.2.4; internally specified boundary on extensions

Related sources S201 S202 S204 S205 S210 S213 S216

N12 · Were between-group differences in change distinguished from endpoint differences and within-group differences?

Current findings: The question was fixed to prioritize the between-group difference in change in FSS, with endpoint differences separate, but monotherapy baseline, change, and endpoint values and the actual analysis are unverified.
Verification status: Unverified
Materials actually read: The complete, exactly retained archived summary was actually read; external material and separate earlier original texts were not read in this review
Why unverified: Do not estimate a between-group monotherapy effect from improvement with a multicomponent product or subjective lupus narratives.
Reason for missing information: Do not estimate a between-group monotherapy effect from improvement with a multicomponent product or subjective lupus narratives.
Required materials and conditions: Baseline, change, and endpoint values, definition of between-group comparison, and adjustment/analysis methods
Materials to obtain first: Baseline, change, and endpoint values, definition of between-group comparison, and adjustment/analysis methods
Further research: Compare eligible results tables against the analysis plan to verify estimates and denominators for the effect of interest.
Remaining uncertainty: Do not estimate a between-group monotherapy effect from improvement with a multicomponent product or subjective lupus narratives.
Conditions for verification: Indicate the between-group/within-group and change/endpoint definitions of the actual selected results and the gaps.
Why this condition is needed: Needed to avoid turning within-group improvement into an effect superior to placebo.
Application exceptions: Do not fill in an analysis not specified in the original text as ITT or an adjusted effect.
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 S201 S205 S207

N13 · Are the directly relevant FSS effect, CI, and P value known?

Current findings: The primary_effect.mean_difference, confidence_interval, p_value, and analysis sample-size records are empty/not_verified.
Verification status: Unverified
Materials actually read: The complete, exactly retained archived summary was actually read; external material and separate earlier original texts were not read in this review
Why unverified: No graphs, correlations, variances, or effect estimates were newly calculated or reconstructed.
Reason for missing information: No graphs, correlations, variances, or effect estimates were newly calculated or reconstructed.
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: Obtain estimates, intervals, variances, and denominators from the original results tables and attribute them to the reported effect definition.
Remaining uncertainty: No graphs, correlations, variances, or effect estimates were newly calculated or reconstructed.
Conditions for verification: Distinguish empty values in primary_effect from the direction of related reports.
Why this condition is needed: Needed to avoid filling in an effect based on significance or the number of related studies.
Application exceptions: Do not turn an unverified result into an effect of 0, nonsignificance, or equivalence.
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 S201 S205 S207

N14 · How many participants were allocated, analyzed, and completed, respectively?

Current findings: Arm-specific allocation, FSS analysis, and completion denominators in directly eligible monotherapy trials are unverified. Known denominators from related trials remain attributed only to each respective study.
Verification status: Unverified
Materials actually read: The complete, exactly retained archived summary was actually read; external material and separate earlier original texts were not read in this review
Why unverified: No effect or incidence rate was calculated without a denominator.
Reason for missing information: No effect or incidence rate was calculated without a denominator.
Required materials and conditions: Arm-specific allocation, analysis, completion, and missing-data/dropout handling in an eligible monotherapy trial
Materials to obtain first: Arm-specific allocation, analysis, completion, and missing-data/dropout handling in an eligible monotherapy trial
Further research: Compare participant flow, reasons for missing data, and outcome-specific analysis tables to verify denominators.
Remaining uncertainty: No effect or incidence rate was calculated without a denominator.
Conditions for verification: Distinguish eligible outcome-specific denominators from what remains unverified.
Why this condition is needed: Needed to avoid using another trial's total sample size as the directly relevant FSS analysis denominator.
Application exceptions: Do not transfer Ullah 58 or Brouwers 53/48 as monotherapy 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

Related sources S201 S202 S204 S205

N15 · Are allocation, concealment, and assessment procedures in the direct comparison known?

Current findings: The preserved materials include related multicomponent-product RCTs, but allocation, concealment, and blinding in a direct monotherapy FSS comparison are unverified.
Verification status: Unverified
Materials actually read: The complete, exactly retained archived summary was actually read; external material and separate earlier original texts were 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 assessor/participant blinding
Materials to obtain first: Actual design, allocation/concealment, baseline balance, and assessor/participant blinding
Further research: Review the scope of verification of allocation and outcome measurement using eligible methods, registrations, and baseline/assessment materials.
Remaining uncertainty: Do not label this as formal execution of RoB 2 or absence of bias.
Conditions for verification: Link actual design/measurement information for the direct results with the missing material.
Why this condition is needed: Needed to avoid using a related RCT label as a bias assessment of an eligible monotherapy trial.
Application exceptions: Do not arbitrarily 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 S201 S205

N16 · Were the effects of ITT/PP, adherence, rescue treatment, and missing data verified?

Current findings: Adherence, arm-specific analyses, and handling of missing data/rescue treatment in eligible monotherapy trials are unverified.
Verification status: Unverified
Materials actually read: The complete, exactly retained archived summary was actually read; external material and separate earlier original texts were not read in this review
Why unverified: The reporting of completers in a related multicomponent-product trial does not verify missing-data handling for monotherapy results.
Reason for missing information: The reporting of completers in a related multicomponent-product trial does not verify missing-data handling for monotherapy results.
Required materials and conditions: Effect of interest, analysis population, adherence, arm-specific changes, and missing-data handling
Materials to obtain first: Effect of interest, analysis population, adherence, arm-specific changes, and missing-data handling
Further research: Match the analysis plan, adherence, and participant flow with results tables to distinguish the actual effect of interest.
Remaining uncertainty: The reporting of completers in a related multicomponent-product trial does not verify missing-data handling for monotherapy results.
Conditions for verification: Indicate the directly eligible analysis and why verification is not possible.
Why this condition is needed: Needed to avoid mixing the effect of assignment with effects among adherent participants or before-and-after results among completers.
Application exceptions: Do not arbitrarily assume ITT if the analysis method is unavailable.
Referenced methods: M03 §3.2.3, M08 §8.2.2–8.2.3; internal application; M08 §8.2.2, M15 §15.3.1; internal application; M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptations are internally designed

Related sources S201 S205

N17 · What magnitude of fatigue difference does the interval allow?

Current findings: The direct between-group FSS CI, variance, and MCID are unverified. The remaining precision axis is also an unscored empty value in the original material.
Verification status: Unverified
Materials actually read: The complete, exactly retained archived summary was actually read; external material and separate earlier original texts were not read in this review
Why unverified: Do not use an unverified interval as evidence excluding an important effect or establishing an effect of 0.
Reason for missing information: Do not use an unverified interval as evidence excluding an important effect or establishing an effect of 0.
Required materials and conditions: Direct effect/CI, endpoint-specific variance, and the basis for an MCID
Materials to obtain first: Direct effect/CI, endpoint-specific variance, and the basis for an MCID
Further research: Obtain the basis for an important difference appropriate to the endpoint version and the actual result interval separately, and compare them.
Remaining uncertainty: Do not use an unverified interval as evidence excluding an important effect or establishing an effect of 0.
Conditions for verification: Explain the reported interval and importance criterion, or why interpretation is not possible.
Why this condition is needed: Needed to avoid declaring sufficiency based only on sample size, statistical significance, or the number of reports.
Application exceptions: Do not arbitrarily adopt an MCID, minimum sample size, or common duration.
Referenced methods: M15 §15.3.1–15.3.3; internal 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 S201 S205

N18 · What produced the FSS improvement in Ullah?

Current findings: Ullah 2023 allocated 58 participants, 29 per arm, to study a product containing pomegranate extract, B-complex vitamins, and vitamin C, and reported FSS improvement. Assessments at 28 days and 56 days were distinguished from follow-up. FSS analysis denominators, completion counts, and the contribution of B5 alone are unverified.
Verification status: Partly verified
Materials actually read: The complete, exactly retained archived summary was actually read; external material and separate earlier original texts were not read in this review
Why unverified: The positive combination-product results were neither deleted nor elevated to a direct single-ingredient effect.
Reason for missing information: The positive combination-product results were neither deleted nor elevated to a direct single-ingredient effect.
Required materials and conditions: Product composition, endpoints, time points, and arm-specific results in the 58-participant trial
Materials to obtain first: Product composition, endpoints, time points, and arm-specific results in the 58-participant trial
Further research: Review the combination trial's original tables, composition, and whether individual factors were compared to verify whether an independent B5 contribution can be estimated.
Remaining uncertainty: The positive combination-product results were neither deleted nor elevated to a direct single-ingredient effect.
Conditions for verification: Link the positive results with the actual combination product and denominator limitations.
Why this condition is needed: Needed to limit attribution to a single ingredient while preserving favorable related results.
Application exceptions: Do not isolate a contribution from B5 solely because it was included.
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; 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; M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses is this project's own design; M03 §3.2.3, M08 §8.2.2–8.2.3; internal application

Related sources S201 S202

N19 · Are the Ullah full text, abstract, and preliminary evaluation independent replications?

Current findings: S201 and S202 are the full text/abstract of the same Ullah RCT and have the same DOI and PMID. S203 is a citation concerning chemical characterization and preliminary evaluation, and the details of its original text are unverified.
Verification status: Partly verified
Materials actually read: The complete, exactly retained archived summary was actually read; external material and separate earlier original texts were not read in this review
Why unverified: S203 was not added as an independent single-ingredient FSS trial, and its exact cohort relationship was not established.
Reason for missing information: S203 was not added as an independent single-ingredient FSS trial, and its exact cohort relationship was not established.
Required materials and conditions: S201/S202/S203 report identities, DOI/PMID, and cohort linkage
Materials to obtain first: S201/S202/S203 report identities, DOI/PMID, and cohort linkage
Further research: Trace the registration, recruitment, product, and participant relationships for each report to check for overlap.
Remaining uncertainty: S203 was not added as an independent single-ingredient FSS trial, and its exact cohort relationship was not established.
Conditions for verification: Distinguish the explicit identity of reports of the same trial from the unresolved relationship with the preliminary evaluation.
Why this condition is needed: Needed to avoid counting reports as unique trials.
Application exceptions: Do not establish cohort linkage for the preliminary evaluation solely from similar names.
Referenced methods: Distinction between studies and reports in M04 §4.6.1–4.6.2; cohort/outcome linkage is an internal 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; internal application

Related sources S201 S202 S203

N20 · Does nonsignificance in Brouwers mean that B5 alone is ineffective?

Current findings: Brouwers 2002 is a trial of a polynutrient supplement in CFS patients and did not report a significant between-group difference in CIS fatigue or other outcomes. It is directly ineligible for the question of B5 alone and FSS.
Verification status: Partly verified
Materials actually read: The complete, exactly retained archived summary was actually read; external material and separate earlier original texts were not read in this review
Why unverified: The nonreporting wording in the original evidence.result and the explanation of nonsignificance in the main text are preserved at their respective locations, without converting them into an effect of 0 for the single ingredient.
Reason for missing information: The nonreporting wording in the original evidence.result and the explanation of nonsignificance in the main text are preserved at their respective locations, without converting them into an effect of 0 for the single ingredient.
Required materials and conditions: CIS, design, between-group results, and original tables for the CFS combination product
Materials to obtain first: CIS, design, between-group results, and original tables for the CFS combination product
Further research: Check the original CIS results and analysis, composition, and population materials to limit direct attribution to FSS.
Remaining uncertainty: The nonreporting wording in the original evidence.result and the explanation of nonsignificance in the main text are preserved at their respective locations, without converting them into an effect of 0 for the single ingredient.
Conditions for verification: Link the differences in population, combination product, and CIS with the scope of the nonsignificant findings.
Why this condition is needed: Needed to preserve unfavorable related findings as well and avoid converting them into an effect of 0 for a different question.
Application exceptions: Do not turn nonsignificance into equivalence or ineffectiveness for all fatigue.
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; M04 §4.6.1–4.6.2, M15 §15.3.1; internal application

Related sources S204 S205

N21 · What denominators do 53 allocated and 48 completed represent?

Current findings: Brouwers allocated 53 participants (27/26), and 48 completed. These are denominators for the CFS combination product, not FSS analysis denominators for B5 alone.
Verification status: Partly verified
Materials actually read: The complete, exactly retained archived summary was actually read; external material and separate earlier original texts were not read in this review
Why unverified: No new arm-specific completion counts or direct FSS denominators were estimated beyond the preserved values.
Reason for missing information: No new arm-specific completion counts or direct FSS denominators were estimated beyond the preserved values.
Required materials and conditions: Brouwers arm-specific allocation, completion, outcome-specific analyses, and handling of dropouts
Materials to obtain first: Brouwers arm-specific allocation, completion, outcome-specific analyses, and handling of dropouts
Further research: Compare participant flow with the CIS analysis population to verify arm-specific missingness and outcome denominators.
Remaining uncertainty: No new arm-specific completion counts or direct FSS denominators were estimated beyond the preserved values.
Conditions for verification: Attribute the original 53 (27/26) allocated and 48 completed to the corresponding combination-product trial.
Why this condition is needed: Needed to avoid merging allocation/completion counts from a related trial into the same analysis denominator.
Application exceptions: Do not calculate new dropout counts or arm-specific 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; internal application

Related sources S204 S205

N22 · Is the improvement in 12 people with lupus a single-ingredient comparison?

Current findings: The 2007 lupus report is a case series in which 12 women received calcium pantothenate 10 g/day together with several vitamins and combination tablets. It describes subjective fatigue improvement; a concurrent comparator and validated between-group FSS results were not verified.
Verification status: Partly verified
Materials actually read: The complete, exactly retained archived summary was actually read; external material and separate earlier original texts were not read in this review
Why unverified: The disease, combined exposure, comparison, and scale all differ from the selected direct question.
Reason for missing information: The disease, combined exposure, comparison, and scale all differ from the selected direct question.
Required materials and conditions: Case populations, concomitant prescriptions, comparator, and validated fatigue scale
Materials to obtain first: Case populations, concomitant prescriptions, comparator, and validated fatigue scale
Further research: Check prescriptions, populations, fatigue collection, and the presence of a comparator for each case to examine the limits of causality/direct applicability.
Remaining uncertainty: The disease, combined exposure, comparison, and scale all differ from the selected direct question.
Conditions for verification: Link the original 12 participants, 10 g/day, and concomitant vitamins with the reasons for direct exclusion.
Why this condition is needed: Needed to avoid turning an uncontrolled multiple-vitamin narrative into a between-group result for a single ingredient.
Application exceptions: Do not convert calcium-salt mass or transfer a disease-specific sample to the target population.
Referenced methods: M03 §3.2.1; detailed population conditions are 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; M08 §8.1–8.2.3; internal application; M03 §3.2.3, M08 §8.2.2–8.2.3; internal application; design considerations in M19 §19.2.2–19.2.4; detailed confounding records are this project's own design

Related sources S207

N23 · Do the cases in the 2004 and 2007 lupus reports overlap?

Current findings: Whether the cases in the 2004 S206 and 2007 S207 lupus reports overlap is unclear. The preserved original text did not add the samples together.
Verification status: Partly verified
Materials actually read: The complete, exactly retained archived summary was actually read; external material and separate earlier original texts were not read in this review
Why unverified: Different journals, years, or URLs are not evidence of independent cases.
Reason for missing information: Different journals, years, or URLs are not evidence of independent cases.
Required materials and conditions: Populations, recruitment, case numbers, periods, and linkage in the two reports
Materials to obtain first: Populations, recruitment, case numbers, periods, and linkage in the two reports
Further research: Compare case tables and periods in the two original reports and record whether they are the same, different, or unresolved.
Remaining uncertainty: Different journals, years, or URLs are not evidence of independent cases.
Conditions for verification: Preserve the original uncertainty about overlap and the principle of not summing the samples.
Why this condition is needed: Needed to avoid counting repeat reports of the same cases as independent replications and additional participants.
Application exceptions: Do not establish that cases differ solely from publication years.
Referenced methods: Distinction between studies and reports in M04 §4.6.1–4.6.2; cohort/outcome linkage is an internal application; M04 §4.6.1–4.6.2, M15 §15.3.1; internal application; M04 §4.6.1–4.6.2; adaptation for harm data is this project's own design

Related sources S206 S207

N24 · Are the rheumatology reviews separate direct trials?

Current findings: S208 and S209 are bibliographic records for reviews concerning rheumatic diseases. Historical review locations identifying the Leung entry, study summaries, and references are preserved.
Verification status: Partly verified
Materials actually read: The complete, exactly retained archived summary was actually read; external material and separate earlier original texts were not read in this review
Why unverified: The two DOIs or review averages were not counted as independent replications of B5 alone for FSS.
Reason for missing information: The two DOIs or review averages were not counted as independent replications of B5 alone for FSS.
Required materials and conditions: Original reports included in S208/S209, linkage to Leung, and overlap
Materials to obtain first: Original reports included in S208/S209, linkage to Leung, and overlap
Further research: Compare family relationships among included-study tables, original reports, and related reviews to link endpoints and repeated citations.
Remaining uncertainty: The two DOIs or review averages were not counted as independent replications of B5 alone for FSS.
Conditions for verification: Distinguish the bibliographic records and historical locations of the two reviews from direct material from original trials.
Why this condition is needed: Needed to avoid double-counting reviews and their included cases as unique trials.
Application exceptions: An indication of historical full-text access to a review is not direct reading in this review.
Referenced methods: Distinction between studies and reports in M04 §4.6.1–4.6.2; cohort/outcome linkage is an internal 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; internal application

Related sources S208 S209 S206 S207

N25 · Is Chalder in BEMS a direct FSS result?

Current findings: ACTRN12613001087741 is a registered trial of a Swisse multicomponent multivitamin in healthy women aged 50~75. Chalder is a different secondary endpoint, and actual randomized counts and results are unverified.
Verification status: Partly verified
Materials actually read: The complete, exactly retained archived summary was actually read; external material and separate earlier original texts were not read in this review
Why unverified: Historical access to the full registration does not mean that the registration was read or direct B5 results were verified in this review.
Reason for missing information: Historical access to the full registration does not mean that the registration was read or direct B5 results were verified in this review.
Required materials and conditions: ACTRN registration, healthy women aged 50~75, multicomponent composition, and endpoint hierarchy/results
Materials to obtain first: ACTRN registration, healthy women aged 50~75, multicomponent composition, and endpoint hierarchy/results
Further research: Link the registration and results report by exact identity to compare the planned Chalder endpoint with the actual results.
Remaining uncertainty: Historical access to the full registration does not mean that the registration was read or direct B5 results were verified in this review.
Conditions for verification: Link the population, combination intervention, secondary endpoint, and unverified actual results.
Why this condition is needed: Needed to avoid elevating the existence of a registration to a target single-ingredient FSS result.
Application exceptions: Distinguish the planned registered sample from actual allocated/analyzed counts.
Referenced methods: M03 §3.2.1; detailed population conditions are 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; 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 Table 8.2.a, M04 §4.6.3; internal application

Related sources S213

N26 · Does a CTG shell mean that results are absent?

Current findings: S214 is a mitochondrial cocktail/Gulf War illness lead, and S215 is an Alii combination-product lead; the direct pages at that time were JavaScript shells.
Verification status: Partly verified
Materials actually read: The complete, exactly retained archived summary was actually read; external material and separate earlier original texts were not read in this review
Why unverified: They were not labeled as verified full texts/results or counted as negative studies.
Reason for missing information: They were not labeled as verified full texts/results or counted as negative studies.
Required materials and conditions: Actual text, interventions/endpoints, and results of NCT02804828 and NCT07271316
Materials to obtain first: Actual text, interventions/endpoints, and results of NCT02804828 and NCT07271316
Further research: In an authorized subsequent update, read the registration text and results and compare the exact products and endpoints indicated by the leads.
Remaining uncertainty: They were not labeled as verified full texts/results or counted as negative studies.
Conditions for verification: Distinguish historical search leads and shells from unverified plans/results.
Why this condition is needed: Needed to avoid turning access failures or shell pages into negative trials or 0 studies worldwide.
Application exceptions: No current access was attempted, and historical shells are not treated as failures 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; M08 Table 8.2.a, M04 §4.6.3; internal application

Related sources S214 S215

N27 · Do mouse fatigue and CoA functions constitute an FSS effect in adults?

Current findings: S210 is a bibliographic record of original-paper metadata/abstract concerning physical fatigue/cognitive dysfunction in mice. CoA/metabolic functions are not direct FSS effects in adults.
Verification status: Partly verified
Materials actually read: The complete, exactly retained archived summary was actually read; external material and separate earlier original texts were not read in this review
Why unverified: Only the preserved metadata/abstract was read; external original experimental tables or effects translated to humans were not verified.
Reason for missing information: Only the preserved metadata/abstract was read; external original experimental tables or effects translated to humans were not verified.
Required materials and conditions: Species, experimental intervention, physiological/behavioral endpoints, and limits of human applicability
Materials to obtain first: Species, experimental intervention, physiological/behavioral endpoints, and limits of human applicability
Further research: State the differences between animal/mechanistic observations and the human clinical question, and do not combine them with direct results.
Remaining uncertainty: Only the preserved metadata/abstract was read; external original experimental tables or effects translated to humans were not verified.
Conditions for verification: Identify nonhuman/mechanistic materials at a separate level, with their original bibliographic locations.
Why this condition is needed: Needed to avoid substituting mechanisms or animal responses for direct human treatment effects.
Application exceptions: Traditional uses or metabolic functions are not eligible between-group effect estimates.
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; this project's own boundary on extensions

Related sources S210 S06

N28 · Can B5 deficiency case reports be used for the same fatigue treatment?

Current findings: S211 is a J-STAGE abstract/search-index bibliographic record of pantothenic-acid deficiency cases. It is not a comparative FSS result for a single active ingredient in nonspecific persistent fatigue.
Verification status: Partly verified
Materials actually read: The complete, exactly retained archived summary was actually read; external material and separate earlier original texts were not read in this review
Why unverified: The existence of human deficiency studies is preserved, but comparisons or effect estimates beyond that abstract are not inferred.
Reason for missing information: The existence of human deficiency studies is preserved, but comparisons or effect estimates beyond that abstract are not inferred.
Required materials and conditions: Deficiency diagnosis, correction, population, and assessment endpoints
Materials to obtain first: Deficiency diagnosis, correction, population, and assessment endpoints
Further research: Check the actual populations, endpoints, and exposures in deficiency/correction cases to examine how they differ from the selected question.
Remaining uncertainty: The existence of human deficiency studies is preserved, but comparisons or effect estimates beyond that abstract are not inferred.
Conditions for verification: Indicate the bibliographic/access level of deficiency cases and the boundaries for direct exclusion.
Why this condition is needed: Needed to distinguish correction of a specific deficiency from additional supplementation for nonspecific persistent fatigue.
Application exceptions: Do not reclassify the material as a comparative FSS trial in adults when original details are absent.
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; 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 S211

N29 · Does the older sports-vitamin material answer the FSS question?

Current findings: S212 is at the bibliographic/search-abstract level for the early sports-vitamin study with PMID4238715 and DOI10.1007/BF00695017.
Verification status: Partly verified
Materials actually read: The complete, exactly retained archived summary was actually read; external material and separate earlier original texts were not read in this review
Why unverified: It was not used as a direct FSS result for B5 alone in nonspecific persistent fatigue.
Reason for missing information: It was not used as a direct FSS result for B5 alone in nonspecific persistent fatigue.
Required materials and conditions: Product composition, populations, exercise/fatigue endpoints, and actual analyses
Materials to obtain first: Product composition, populations, exercise/fatigue endpoints, and actual analyses
Further research: Compare the composition, population, and endpoint tables of the original sports trial to record its differences from the direct question.
Remaining uncertainty: It was not used as a direct FSS result for B5 alone in nonspecific persistent fatigue.
Conditions for verification: Link the verified level of material with the reasons for not attributing it directly.
Why this condition is needed: Needed to avoid substituting exercise performance or vitality wording for FSS in persistent fatigue.
Application exceptions: Do not establish single-ingredient intervention/scale eligibility from bibliographic records or search abstracts.
Referenced methods: M03 §3.2.1; detailed population conditions are 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; M03 §3.2.4; this project's own boundary on extensions

Related sources S212

N30 · Do ME/CFS metabolomic data represent a single-ingredient treatment effect?

Current findings: S216 is a search-index description of ME/CFS metabolomics material, and a CAPTCHA was reported during direct access at that time.
Verification status: Partly verified
Materials actually read: The complete, exactly retained archived summary was actually read; external material and separate earlier original texts were not read in this review
Why unverified: The metabolomic bibliography/association was not used as an FSS treatment effect from administering B5 alone.
Reason for missing information: The metabolomic bibliography/association was not used as an FSS treatment effect from administering B5 alone.
Required materials and conditions: Direction of exposure, disease, metabolomic findings, and whether a direct intervention exists
Materials to obtain first: Direction of exposure, disease, metabolomic findings, and whether a direct intervention exists
Further research: Check the direction and comparative design of observational metabolomic data and separate them from the direct FSS intervention question.
Remaining uncertainty: The metabolomic bibliography/association was not used as an FSS treatment effect from administering B5 alone.
Conditions for verification: Indicate the disease/endpoint level of the search leads and the lack of direct attribution.
Why this condition is needed: Needed to avoid reversing associations or surrogate markers into an effect of administering the ingredient.
Application exceptions: Do not extrapolate metabolomic differences to doses or individual treatment responses.
Referenced methods: M03 §3.2.1; detailed population conditions are 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; 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; this project's own boundary on extensions

Related sources S216

N31 · Do patent examples constitute clinical comparative evidence?

Current findings: S217 is a search-index bibliographic record of examples in patent US5304574A.
Verification status: Partly verified
Materials actually read: The complete, exactly retained archived summary was actually read; external material and separate earlier original texts were not read in this review
Why unverified: Directly eligible between-group FSS results, samples, and independence were not verified from this bibliographic record.
Reason for missing information: Directly eligible between-group FSS results, samples, and independence were not verified from this bibliographic record.
Required materials and conditions: Populations, experiments, and independent clinical results in the US5304574A examples
Materials to obtain first: Populations, experiments, and independent clinical results in the US5304574A examples
Further research: Compare the relationship between the patent lead and actual clinical reports, including whether they concern the same cases, and verify direct evidence separately.
Remaining uncertainty: Directly eligible between-group FSS results, samples, and independence were not verified from this bibliographic record.
Conditions for verification: Link the verified patent search-index level to its original location.
Why this condition is needed: Needed to avoid confusing the existence of a patent with eligible trials or demonstrated efficacy.
Application exceptions: Do not label patent rights/cases as independent replications of efficacy.
Referenced methods: Distinction between studies and reports in M04 §4.6.1–4.6.2; cohort/outcome linkage is an internal 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; Chamgap's own conditions for independence and attribution. The official methods sections used in this pilot do not guarantee all of these detailed items; M04 §4.6.1–4.6.2, M15 §15.3.1; internal application

Related sources S217

N32 · Were preserved archived summaries distinguished from historical full-text access?

Current findings: The complete preserved archived summary for 3101 was actually read in this review. NIH inherited extraction, partial PMC access followed by a CAPTCHA, author uploads, visual PDF inspection, full-text access to reviews/registrations, and search indexes are reports from the manuscript at that time. No external materials were attempted or read in this review.
Verification status: Met
Materials actually read: The complete, exactly retained archived summary was actually read; external material and separate earlier original texts were not read in this review
Why unverified: No report-specific access-date field exists, so it was left empty and distinguished from the original review date of 2026-09-15.
Reason for missing information: No report-specific access-date field exists, so it was left empty and distinguished from the original review date of 2026-09-15.
Required materials and conditions: Identity, current locations/values/SHA read, and historical access/dates for each material
Materials to obtain first: Identity, current locations/values/SHA read, and historical access/dates for each material
Further research: When material acquisition is separately authorized, record access levels, dates, original bytes, and locations read for each report.
Remaining uncertainty: No report-specific access-date field exists, so it was left empty and distinguished from the original review date of 2026-09-15.
Conditions for verification: Indicate the summaries actually read in the current review separately from external materials not attempted/not read, and connect the links.
Why this condition is needed: Needed to avoid turning a URL or historical access into original-paper reading in this review.
Application exceptions: Historical CAPTCHAs, shells, and unacquired material are not current access failures, and access dates are not inferred.
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 S201 S202 S203 S204 S205 S206 S207 S208 S209 S210 S211 S212 S213 S214 S215 S216 S217

N33 · Does no_human_study mean that all human studies are absent?

Current findings: axes.no_human_study=true and human_study_exists=false apply to the fixed direct single-ingredient FSS comparison. related_human_studies_exist=true and search_exhaustive=false are also explicitly stated in the original text.
Verification status: Met
Materials actually read: The complete, exactly retained archived summary was actually read; external material and separate earlier original texts were not read in this review
Why unverified: Do not delete related human studies of combination products/specific diseases or interpret the record as a worldwide absence of human evidence.
Reason for missing information: Do not delete related human studies of combination products/specific diseases or interpret the record as a worldwide absence of human evidence.
Required materials and conditions: Original flags, scope, directly eligible/related human-study existence, and search limitations
Materials to obtain first: Original flags, scope, directly eligible/related human-study existence, and search limitations
Further research: When updating, review the link between direct eligibility, search scope, and code meaning, and distinguish raw values from the current explanation.
Remaining uncertainty: Do not delete related human studies of combination products/specific diseases or interpret the record as a worldwide absence of human evidence.
Conditions for verification: Preserve the original flags together with their semantic limitations and the existence of related human studies.
Why this condition is needed: Needed to avoid reading a code flag as 0 studies worldwide or no effect.
Application exceptions: Do not alter the original true/false/empty values to make them identical.
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; internal application

Related sources S201 S202 S204 S205 S207

N34 · What do ?, empty values, and the subsequent 5 axes mean?

Current findings: The original efficacy grade is ?, the score is empty, and the 7 axes are B/P/empty/empty/empty/empty/empty. The subsequent 5 axes and strength count are unscored, not 0. The document_quality B in the original self-review is also separate.
Verification status: Met
Materials actually read: The complete, exactly retained archived summary was actually read; external material and separate earlier original texts were not read in this review
Why unverified: Condition statuses, report counts, and original document assessments were not turned into new scores or official certification.
Reason for missing information: Condition statuses, report counts, and original document assessments were not turned into new scores or official certification.
Required materials and conditions: Original grade/score, application of each axis, gate rationale, and historical calculation references
Materials to obtain first: Original grade/score, application of each axis, gate rationale, and historical calculation references
Further research: In a future, separately authorized update of the criteria, compare and distinguish the original inputs, rules, actual calculations, and valid judgments.
Remaining uncertainty: Condition statuses, report counts, and original document assessments were not turned into new scores or official certification.
Conditions for verification: Preserve the applied/unscored meaning of the original B/P/5 null axes, ?, and empty score.
Why this condition is needed: Needed to avoid elevating new verification statuses into efficacy grades or scores.
Application exceptions: Do not merge document quality B with efficacy ?, or rerun the original calculator.
Referenced methods: M04 §4.5, §4.6.3; limitations of the current material conversion follow the user's scope and this project's own design; M15 §15.3.1–15.3.3; internal application

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N35 · What is known about products, company-affiliated authors, and funding?

Current findings: For Ullah, the Esserre product and company-employee authorship are reported; for Brouwers, Numico supply/manufacture and author affiliation are reported. Full funding and patent information are unverified. Lupus-study funding is also unverified, and the full Swisse COI information was not reviewed for an efficacy conclusion.
Verification status: Partly verified
Materials actually read: The complete, exactly retained archived summary was actually read; external material and separate earlier original texts were not read in this review
Why unverified: Do not transfer related-product sponsorship information to the independence axis of a single-active-ingredient trial.
Reason for missing information: Do not transfer related-product sponsorship information to the independence axis of a single-active-ingredient trial.
Required materials and conditions: Product provision, manufacture, company affiliations, research funding, patents, and disclosed COI
Materials to obtain first: Product provision, manufacture, company affiliations, research funding, patents, and disclosed COI
Further research: Compare original disclosures, product supply, and funding/employment information by study family, and limit the interpretation of independence.
Remaining uncertainty: Do not transfer related-product sponsorship information to the independence axis of a single-active-ingredient trial.
Conditions for verification: Distinguish the reported Esserre, Numico, and Swisse information from what remains unverified.
Why this condition is needed: Needed to avoid turning partial company information or unverified information into independent funding/independent replication.
Application exceptions: Do not delete results because conflicts of interest exist or treat their absence as 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; M08 §8.1–8.2.3; internal application

Related sources S201 S202 S204 S205 S207 S213

N36 · Was the target FSS outcome prespecified?

Current findings: Preregistration and analysis plans for a direct single-active-ingredient FSS comparison are unverified within the preserved scope. The full related registration and CTG shell are distinct levels of material.
Verification status: Unverified
Materials actually read: The complete, exactly retained archived summary was actually read; external material and separate earlier original texts were not read in this review
Why unverified: Do not establish that selective reporting occurred or that registration was absent from gaps in direct plans.
Reason for missing information: Do not establish that selective reporting occurred or that registration was absent from gaps in direct plans.
Required materials and conditions: Eligible single-active-ingredient trial registration, protocol, SAP, reasons for changes, and all results
Materials to obtain first: Eligible single-active-ingredient trial registration, protocol, SAP, reasons for changes, and all results
Further research: Compare registration/SAP with the actual FSS version, time points, and analyses, and record the scope of changes and nonreporting.
Remaining uncertainty: Do not establish that selective reporting occurred or that registration was absent from gaps in direct plans.
Conditions for verification: Link the plans compared and the scope of direct material not compared to their locations.
Why this condition is needed: Needed to avoid turning the failure to acquire direct plans into confirmation of nonregistration or selective reporting.
Application exceptions: The related BEMS registration is a plan for a different population, product, and scale.
Referenced methods: M08 Table 8.2.a, M04 §4.6.3; internal application; data collection/selection principles in M04 §4.5–4.6; separation of access from reading and the hyperlink contract are internally designed; M04 §4.5, §4.6.3; the limits of the current material conversion follow the user's scope and the project's own design

Related sources S213 S214 S215

N37 · Are optimal dose, persistence, and efficacy in special populations also required?

Current findings: The selected question in this review is the between-group FSS effect in the fixed population. Optimal dose, persistence after discontinuation, and efficacy in all special populations are separate extension questions and were not adopted as additional requirements.
Verification status: Not applicable
Materials actually read: The complete, exactly retained archived summary was actually read; external material and separate earlier original texts were not read in this review
Why unverified: Gaps in verification of the duration and population needed for the claim remain unverified under the earlier items.
Reason for missing information: Gaps in verification of the duration and population needed for the claim remain unverified under the earlier items.
Required materials and conditions: Separate direct dose comparisons, follow-up after discontinuation, and prespecified subgroups/interactions
Materials to obtain first: Separate direct dose comparisons, follow-up after discontinuation, and prespecified subgroups/interactions
Further research: If an extension question is separately requested, review direct dose/follow-up/interaction designs against their plans and results.
Remaining uncertainty: Gaps in verification of the duration and population needed for the claim remain unverified under the earlier items.
Conditions for verification: Record separately the nonapplicability boundary for extensions of efficacy beyond the direct question and what remains unverified.
Why this condition is needed: Needed to avoid extending the narrow FSS question to all long-term and optimal-dose claims.
Application exceptions: The actual duration relevant to the assessed claim must be verified, but optimal-dose/all-subgroup trials are not imposed as additional requirements.
Referenced methods: M03 §3.2.1–3.2.4; details of dose, persistence, and effect modification are internally designed; M03 §3.2.4; internally specified boundary on extensions; question-clarification principles in M03 §3.1, §3.2.1–3.2.4; detailed separation rules are internally designed

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N38 · How much is known about diarrhea and discontinuations with the same single-active-ingredient exposure?

Current findings: The original preserved NIH description mentions the possibility of diarrhea and gastrointestinal discomfort with high-dose B5. The 10 g/day example is not a toxicity threshold/dosing recommendation, and the adequate intake of 5 mg/day is a nutritional reference value. Harm collection, arm-specific denominators/discontinuations, and causality for a single active ingredient used for this fatigue purpose are unverified.
Verification status: Partly verified
Materials actually read: The complete, exactly retained archived summary was actually read; external material and separate earlier original texts were not read in this review
Why unverified: The absence of an established upper limit does not mean unlimited safety. Do not transfer combination-product adverse effects or pantethine bleeding cautions to B5 alone.
Reason for missing information: The absence of an established upper limit does not mean unlimited safety. Do not transfer combination-product adverse effects or pantethine bleeding cautions to B5 alone.
Required materials and conditions: Event definitions, collection, exposure, time, denominators, arm-specific discontinuations, and concomitant use/causes
Materials to obtain first: Event definitions, collection, exposure, time, denominators, arm-specific discontinuations, and concomitant use/causes
Further research: Separately review systematic harm/discontinuation, concomitant-use, and follow-up data for the same single-active-ingredient product and population.
Remaining uncertainty: The absence of an established upper limit does not mean unlimited safety. Do not transfer combination-product adverse effects or pantethine bleeding cautions to B5 alone.
Conditions for verification: Distinguish the NIH high-dose GI warning from gaps in denominators/methods for direct target harms.
Why this condition is needed: Needed to avoid converting general safety commentary into incidence rates in the target single-active-ingredient trial or overall safety.
Application exceptions: Do not turn unverified efficacy into safety or copy cautions for combination products/pantethine.
Referenced methods: M19 §19.1.2–19.2.4; internal application; M19 §19.1.2–19.2.4; detailed distinctions are internally designed; design-specific harm questions in M19 §19.2; details of temporal relationships are internally designed; M19 §19.2.2–19.2.4, M03 §3.2.3; internal application; design considerations in M19 §19.2.2–19.2.4; detailed confounding records are internally designed; M19 §19.1.2–19.2.4, M04 §4.6.3; internal 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

N39 · Has safety been verified for long-term high-dose use, special populations, and concomitant use?

Current findings: Safety for long-term high-dose use for this fatigue purpose, pregnancy, lactation, children, and liver/kidney disease is unverified. The statement that no important interactions are known is also not proof of safety for all combinations.
Verification status: Unverified
Materials actually read: The complete, exactly retained archived summary was actually read; external material and separate earlier original texts were not read in this review
Why unverified: Do not turn study doses into personal dosing instructions or calculate incidence rates from general warnings.
Reason for missing information: Do not turn study doses into personal dosing instructions or calculate incidence rates from general warnings.
Required materials and conditions: Data on long-term exposure, rare events, pregnancy/lactation/children, liver/kidney disease, and concomitant use
Materials to obtain first: Data on long-term exposure, rare events, pregnancy/lactation/children, liver/kidney disease, and concomitant use
Further research: Review long-term/vulnerable-population and concomitant-use studies with matching exposure and baseline risk in relation to their separate designs and actual collection methods.
Remaining uncertainty: Do not turn study doses into personal dosing instructions or calculate incidence rates from general warnings.
Conditions for verification: Preserve the safety limitations for the selected fatigue purpose and the original Caution label.
Why this condition is needed: Needed to avoid using limited general descriptions as proof of safety for all populations/combinations.
Application exceptions: Do not establish that unverified interactions are absent.
Referenced methods: M19 §19.1.2–19.2.4; internal 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

N40 · What can change, as of which date and within which material scope?

Current findings: The evidence/original review date is 2026-09-15. This conversion of preserved material into a table is not a new search, external full-text reading, calculation, judgment, or deployment. If new single-active-ingredient trials, composition, fatigue tables, registration/SAP, corrections/retractions, or classification/numerical errors are verified, preserve the prior original text and history at the same ID/URL.
Verification status: Met
Materials actually read: The complete, exactly retained archived summary was actually read; external material and separate earlier original texts were not read in this review
Why unverified: The original document_quality B, grade_revalidated, and single-assistant self-review are original reports, not independent clinical certification in this review.
Reason for missing information: The original document_quality B, grade_revalidated, and single-assistant self-review are original reports, not independent clinical certification in this review.
Required materials and conditions: Original review date, scope actually read in the current review, new evidence/corrections, and preservation of versions/original text
Materials to obtain first: Original review date, scope actually read in the current review, new evidence/corrections, and preservation of versions/original text
Further research: In a separately authorized update event, preserve the identity of new material, the full original text, and before/after values, and review linked conditions again.
Remaining uncertainty: The original document_quality B, grade_revalidated, and single-assistant self-review are original reports, not independent clinical certification in this review.
Conditions for verification: Distinguish the original date and self-review, what has not been newly performed, and the conditions for updates/the same ID.
Why this condition is needed: Needed to avoid overstating the current table conversion as a current comprehensive search, publication, or official certification.
Application exceptions: The original first_published_at is an editorial reference date, not proof of actual server deployment.
Referenced methods: M04 §4.5, §4.6.3; the limits of the current material conversion follow the user's scope and the project's own design; data collection/selection principles in M04 §4.5–4.6; separation of access from reading and the hyperlink contract are internally designed; M04 §4.6.3, M15 §15.3.1–15.3.3; status distinctions are internally designed

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