Does oral single-active pantothenic acid improve TEWL in adults with dry, impaired-barrier skin?

Complete submitted research report

# Does oral single-active pantothenic acid improve TEWL in dry, barrier-impaired adult skin?

**TASK-1033 / R01-073 · 5/5 · Evidence cutoff: 2026-09-17**

## The 30-second answer

Within the disclosed search, **no eligible human comparison was verified that isolated the effect of oral single-active pantothenic acid on transepidermal water loss (TEWL) at a defined time in adults with dry, barrier-impaired skin.** Related human research does exist. In an oral combination trial, both conditions received the same pantothenic acid; topical panthenol or dexpanthenol results do not establish the effect of taking pantothenic acid orally. [S01,S03,S05,S13,S14]

The current efficacy judgment is **`?`, with score `null`**, and safety is **Caution**. This is not zero effect, equivalence, a score of zero, or absence of all human pantothenic-acid research. A directly applicable oral effect, its between-group confidence interval (CI), and a minimum clinically important difference (MCID) cannot be estimated from the material verified. **Document quality A** describes same-author completeness of sourcing, boundaries, uncertainty, bilingual content and format; it is not independent peer review, journal certification or an error-free guarantee.

## 1. The question is not a verified trial description

| Dimension | Intended question | Verified boundary | |---|---|---| | Substance and route | Oral single-active pantothenic acid | Pantothenic acid and calcium/sodium salts are not automatically converted between labeled and active amounts. An eligible oral product's salt, dose and duration remain unverified. | | Population | Adults with defined dry skin and impaired barrier function | Healthy volunteers, clinically dry skin, and SLS/SLES damage models are distinguished. Dryness alone is not proof of elevated TEWL. | | Endpoint | TEWL at a defined time | Water flux through skin is not the same numerical endpoint as stratum corneum hydration, Corneometer/Skicon readings, elasticity, erythema or subjective symptoms. | | Comparator | Actual placebo, usual care or active control | No eligible single-B5 oral contrast was verified. An untreated leg, vehicle and oral control containing the same vitamins are not interchangeable placebos. | | Clinical interpretation | A barrier-related surrogate | A change in TEWL alone does not establish eczema treatment, itch relief, ulcer closure or long-term clinical benefit. |

Proposed eligibility, dose, duration and comparator have not been turned into study facts. Deficiency correction is not combined with extra supplementation in people whose nutrient status is unknown. Confirmed findings and reasons for unavailable baseline nutrition, total diet/supplement exposure, renal function, disease, season and concomitant care appear separately in `study_extractions.json`.

## 2. Reuse and duplicate review

The complete **3,148-record index** was screened using Korean/English names, synonyms and adjacent endpoints, and the seven included originals **028, 3099, 3100, 3101, 3102, 3147 and 3148** were reviewed. These concern broad acne/hair material, inflammatory acne counts, LDL-C, FSS fatigue, diarrhea risk, complete epithelialization of chronic ulcers and stratum corneum hydration, respectively. Their independent claims differ from this TEWL question. The presence of TEWL sources in 3148 does not mean this oral independent claim was already published. Index-only pantethine/lipid and topical multiingredient eyelid-cleansing records were also distinguished by molecule, route and endpoint. Automatic candidate presence or absence was not treated as a guarantee of novelty.

The current input records prior72 as **published3148**, with **72 completed tasks:67 published,5 exact duplicates and 28 pending**. These are supplied deployment/completion records, not a claim of new live-server verification by this researcher. The historical unassigned manifest and all original bytes remain unchanged. Completed71/72 and B6 manuscripts, grades and translations were not modified. The3148 source, search, extraction and safety map was reused; only gaps specific to the new TEWL question were investigated.

## 3. Search and access scope

Public searches on 2026-09-17 combined pantothenic acid, pantothenate, calcium/sodium salts, oral administration, xerosis and TEWL/transepidermal water loss, including Korean terms. Topical synonyms, unfavorable/nonsignificant findings, trial registration and correction/retraction terms were searched separately. **Forty actual search expressions** are retained in `search_log.json`. PubMed/PMC, primary publishers, UMIN, public ClinicalTrials.gov records, ISRCTN-index searching and official device/safety information were used. Full-text/PDF-table access is distinguished from abstract-only and bibliographic access.

The interface did not provide a stable exhaustive result count, so a global hit count remains `null`. No artificial PRISMA counts or zero-result claims were created. Among the **ten human study/case records reviewed**, zero met the direct comparison criteria. The14 source records include linked registries and nontrial device/safety information, not14 independent trials. Licensed Embase/Scopus searches, all unpublished material, every registry version and participant-level data were not reviewed. This is a reproducible bounded search, not proof that no relevant study exists anywhere.

## 4. Evidence table

| Study and actual design | Population, denominator and period | Finding and directness | Funding, product and access | |---|---|---|---| | **Takaoka 2019 [S13,S14]**, oral amino acids plus multivitamins versus the same multivitamins; randomized double-blind crossover | 29 healthy Japanese women; initial sequences14/15. The29 observations in each condition are the same people's crossover exposures. Six weeks per condition reported | Both conditions supplied11 mg/day pantothenic acid. Neck TEWL fell within both; no significant intercondition difference was reported. No B5 exposure contrast | UMIN names Noevir and DAC as funders. Noevir sample preparation/affiliated authors and the article's no-conflict declaration are both reported. Full text, tables and current registry accessed | | **Morgado 2026 [S05,S09]**, randomized split-leg topical combination cream versus untreated skin | 35 people/35pairs;28 days;35 completed; efficacyPP35 and safetyITT35 | Table 2 day 28 TEWL7.9 treated versus 9.5 untreated g/m²/h. Topical, multiingredient and no vehicle control. Dryness selection is not elevated-TEWL selection | Lacer funding and three affiliated authors. Donation details unverified. Primary text/tables/figure accessed; original registry history unavailable | | **Gehring & Gloor 2000 [S01]**, topical randomized double-blind vehicle comparison | Seven days; sample size and xerosis criteria absent from accessed abstract | Lower TEWL and higher hydration reported. Numerical contrast/CI unavailable; not an oral result | Funding and product supply absent from abstract; full-text access limited | | **Camargo 2011 [S03]**, topical0/0.5/1/5% formulations and SLES washing | Healthy forearm skin,15/30 days and 2 hours after washing; N/attrition unavailable in abstract | Lower30-dayTEWL with 1/5% and favorable postwash findings for panthenol formulations. Not an oral effect | Funding/product detail and numerical magnitude/CI unavailable in abstract | | **Pavlackova 2018/2019 [S06]**, topical emulsion comparisons | 40 women,48 hours,5–13 wt%panthenol | Some7–11 wt% formulations lowered TEWL. Exact contrast/CI and xerosis selection unverified | Abstract-level access; funding, supply and analysis sets unverified | | **Proksch & Nissen 2002 [S10]**, topical cream after SLS damage versus vehicle/untreated control | Patch-damage model; twice daily; N and total period unverified from abstract | Faster barrier repair reported; exact TEWL device/value not established by the accessed abstract | PubMed abstract; publisher full text inaccessible. Support indexing does not identify a funder or independence | | **Biro 2003 [S02]**, topical5%dexpanthenol, paired forearms | 25 people,21 completed;3noncompliance and 1unrelated severe-AE withdrawal;26 days | Corneometry, sebum and pH are not substituted for TEWL. Topical acute-SLS boundary | Existing abstract extraction reused; funding/supply unreported | | **Fanian 2013 [S04]**, oral multinutrient/placebo | 80allocated40/40; outcomes40/39;122 days plus6 weeks off treatment | Actual microrelief, elasticity and ultrasound outcomes; not oral single-B5 TEWL evidence | Vitabiotics product; explicit funding/donation unverified; prior full-text extraction reused | | **Rao 2021 [S07]**, oral pharmacokinetics/safety | 40unique healthy adults:32 single-dose and 8 separate repeat-dose participants | No TEWL endpoint; existing dose/feeding/diarrhea denominators reused for safety only | CoA Therapeutics funding/interests; Rugby product; prior extraction reused | | **Hemmer 1997 [S11]**, bibliographic case of hand eczema with oral exposure | Title identifies one dexpanthenol-sensitized patient | Safety caveat only. Dose, provocation, causality and frequency cannot be established without the narrative | Bibliography/case indexing only; full narrative and funding unavailable |

## 5. The key oral adjacent trial: B5 was also in the control

Takaoka's Table 2 supplies **5.5 mg pantothenic acid per pack, two packs daily, or11 mg/day in both products**. The experimental condition additionally supplied leucine1200 mg/day, arginine500 mg/day and glutamine600 mg/day. The control replaced only those amino acids with maltitol; the other vitamins were unchanged. Calling the paper's placebo a B5-free placebo would therefore be incorrect. The chemical salt, active-acid labeling basis and total dietary B5 intake were not established. These research exposures are not personal dosing recommendations. [S13,Table 2]

The registry targeted30 participants; the article enrolled29. That difference was not invented as a one-person dropout. Mean age22.2±3.4 is **SD**. Participants were healthy women without treated problematic disease, regular pharmaceuticals/supplements or smoking; they were not selected by xerosis, impaired-barrier or deficiency criteria. Neck moisture was an allocation factor, with 14/15 initial sequences. The29 observations per condition are not58 independentpeople, and anatomical sites or repeated visits are not additional patients. [S13,Table 1/Methods;S14]

TEWL was measured using **TewameterTM 300** at a fixed neck landmark and the inner forearm. After light washing with a designated detergent, participants sat for **20 minutes of acclimation at 21±1°C and 55±10%relative humidity**. The open-chamber principle was confirmed from the manufacturer, not inferred as evidence of actual trial calibration. Airflow/sweat controls, probe-stability criteria, TEWL replicate count/averaging and a precise moisturizer-restriction interval were not reported. The paper's five measurements describe colorimetry, not TEWL. Skicon hydration and Cutometer elasticity remain different endpoints. [S12,S13,Methods]

| NeckTEWL, g/m²/h; mean ±SD | Baseline | Week2 | Week4 | Week6 | |---|---:|---:|---:|---:| | Same-vitamin control | 9.0±5.0 | 7.5±3.6 | 7.5±2.5 | 6.7±2.3 | | Amino acids plus same vitamins | 8.3±3.4 | 8.2±3.6 | 7.4±2.6 | 6.6±2.0 |

The significance symbols in Table 4 concern within-condition comparisons against baseline. The authors describe **no significant intercondition difference in neck TEWL**; an exact between-condition TEWL p value or CI was not available. Arithmetic from rounded means gives changes of−1.7 and−2.3, and a difference of changes of+0.6g/m²/h. This is not a crossover estimate adjusted for period, sequence and within-person correlation, and is not a B5 effect. Nonsignificance is not equivalence. Numerical forearmTEWL data were not shown and were not filled in. [S13,Table 4/Results;numeric_audit.json]

Measurements were at 0,2,4 and 6 weeks in each condition. The authors describe six-week periods and a two-month washout, but provide calendar dates of 2015-05-26to07-09 and 10-21to12-17. These were not forced into agreement without individual schedules. Seasonal differences, unreported period/carryover adjustment, multiple endpoints/times, and unreported formal ITT, missing-data handling and adherence rates limit interpretation. Current registryversion3 reports disclosure on 2015-05-19 and update on 2018-04-08; the primary endpoint is broadly **skin state**, not a uniquely specified TEWL/time hierarchy. Historical versions were not verified. Its2018unpublished field is not evidence that the 2019paper does not exist. The registry names **Noevir and DAC** as funders; the article acknowledges Noevir test-sample preparation while declaring no potential conflicts. [S13,S14]

One S13 design paragraph names asparagine, whereas Table 2 and the test-product description name arginine. Composition reported here explicitly follows **Table 2**, without silently harmonizing the conflicting wording. This limitation does not create an independent B5 contrast. [S13,pp53–54]

## 6. The topical xerosis trial: paired data and unreconciled numbers

Morgado's trial applied a cream containing panthenol, niacinamide and dipotassium glycyrrhizate to one leg at **1g product twice daily for 28 days**, leaving the opposite leg untreated. Individual concentrations and active amounts were not verified. Neutral detergent was common care, but absence of vehicle control prevents isolation of emollient/occlusive effects and individual ingredients. Dryness selection used stratum corneum hydration, not a verified elevated-TEWL criterion. BaselineTEWL was9.2g/m²/h on both sides; participants were not relabeled as a threshold-confirmed high-TEWL damage cohort. [S05]

All35 participants completed; the paper describes **efficacyPP35 and safetyITT35**. A computer-generated sequence allocated the treated leg. The clinical dermatologist was blinded, but participants could recognize the untreated side; instrument-operator blinding and allocation-concealment details were unverified. Container weights and interviews checked use, without a reported adherence percentage. Measurements involved20×10cm pretibial regions, **TM 300,22±2°C,50±10%relative humidity and 15 minutes acclimation**. TEWL times were baseline,30 minutes,24 hours,48 hours,7 days and 28 days. Calibration, airflow, sweating, probe stabilization, replicate counts, and the interval from last application/removal or washing to measurement were not adequately established in the accessible account. [S05,Methods;S12]

| Table 2 TEWL, g/m²/h | Baseline mean ±SE[95% CI of mean] | Day7 | Day28 | |---|---|---|---| | Treated leg | 9.2±0.3[8.6,9.8] | 8.1±0.2[7.7,8.5] | 7.9±0.2[7.5,8.3] | | Untreated leg | 9.2±0.3[8.6,9.8] | 9.3±0.3[8.7,9.9] | 9.5±0.3[8.9,10.1] |

Dispersion is **SE**, not SD. The intervals describe individual means, not the paired between-treatment change. Table 2 reports a day 28between-legp <0.001, a treated within-baselinep <0.001 and untreatedp =0.111. Rounded-mean arithmetic gives treatedchange−1.3, untreatedchange+0.3 and differenceofchanges−1.6g/m²/h. These are descriptive calculations, not an adjusted estimate. No CI was reconstructed without paired covariance. [S05,Table 2]

**Published discrepancies remain explicit.** The abstract gives day 7as8.2±0.2[7.8,8.6]with 11.3%reduction; the body/Table 2 give8.1±0.2[7.7,8.5]and 12.0%. Day28reduction is13.5%in the abstract versus 14.1%in the body. At24 hours the body gives 8.6while Figure 2B labels 8.5. The48-hour within-group significance symbol also differs from the body statement. Within-group and between-leg symbols concern different tests. The table above explicitly uses **Table 2**, not a silently harmonized replacement. The cause of these differences cannot be established without data or an official explanation. [S05,Abstract/Results/Figure 2B/Table 2]

The prior72 findings about age dispersion, hydration-percentage definitions and hydration-measurement times were reused as historical discrepancies. The completed hydration manuscript was not corrected or regraded here. Favorable topical findings are disclosed as adjacent/countervailing material, not promoted to oral evidence. Repeated-measuresANOVA and local Tukey-Kramer procedures do not establish overall multiplicity control across every endpoint/time; the paper acknowledges this limitation. [S05;provided prior72 verification report]

## 7. Safety and total exposure

**Caution.** Comparative safety for the eligible oral intervention is unavailable. No observed acute irritation in 35 topical participants over 28 days does not establish oral safety. S13 did not provide usable systematic adverse-event counts or discontinuation causes for both conditions; this was not described as zero events. [S05,S13]

The existing oral pharmacokinetic extraction identifies40unique people. Diarrhea was reported in 1/8 after a fasting5000 mg-labeled single exposure,0/8 after fed re-exposure in the same 8 people, and 0/8in a separate8-person2000 mg/day 14-day repeat-dose cohort. Fed/fasting observations were not counted as 16 independent participants. Follow-up to day 22was not converted into22 days of dosing. Without placebo and with an unresolved acid/salt labeling basis and total intake, no causalRR,NNH or safe-dose threshold was calculated. CoA Therapeutics funding and employment/consultancy/shareholding interests were preserved. [S07;reuse from 3102/3147/3148]

Hemmer's oral-pantothenic-acid/hand-eczema case was available as bibliographic metadata only. The title's sensitized-patient context is a cautionary signal, not verification of dose, challenge testing, causality or incidence. The previous same-day NIHODS extraction states that absentUL reflects insufficient data and discusses gastrointestinal effects at very high intakes. Current reopening returned403/access errors, so it is not represented as a newly accessed full page. No UL or no known interaction does not demonstrate unlimited or universally compatible use. [S08,S11]

Total dietary and multicomponent-product exposure, prolonged use, pregnancy/lactation, children, hepatic/renal disease, specific drug combinations and laboratory interference are insufficiently established for this question. Pantothenic acid, topical dexpanthenol and pantethine are not merged into one intervention. **Research doses are not personal instructions and do not replace or change moisturization or standard treatment for skin disease.**

## 8. Classification, grade and uncertainty

The classification is `kind=S`,category`skin-hair`,claim_type`B`, with intended surrogate endpoint`S`. The supplied stage-0 rule and **unchanged original calculator** were executed: proposed and final grades both equal **`?`**, with **score`null`**. No A–F numerical anchor was assigned to this category. Replication, independence, effect, bias, precision and unscored sub-boundaries were not assigned invented grades or zeros. Execution results and source-file hashes appear in `grading_result.json`.

The `no_human_study=true` flag is restricted, after actual design/directness review, to **no verified independent comparison for this oral-single/dry-barrier/defined-timeTEWL question within the disclosed public search**. A separate field states that related oral and topical human studies exist. S13 gave oral B5 and measuredTEWL in humans, but equal B5in both conditions prevents testing its independent effect. Topical trials have a different route. Inaccessible full text alone did not trigger this flag.

The isolated oral effect's direction and magnitude are not estimable; certainty of an oral clinical benefit inferred from adjacent data is very low. This is not formal GRADE, a treatment-success probability or a finding of no effect. An applicableTEWL CI orMCID was not verified, and continuous surrogate data were not converted into event-basedARR/NNT.

## 9. Self-review, revisions and completion

The same author checked primary text/abstracts and PDF tables/figures, person/pair/repeated-measure denominators, equal-B5controls,SD versus SE and CI types, actual registration/funding, molecule/route/endpoint boundaries, the original calculator, bilingual numerical/uncertainty agreement and site fields. S13funding was updated before submission from the article-only state of exact funding unverified to **registry-confirmed funders**. S05's24-hour and abstract/table conflicts were made explicit before completion. These are prepublication audit actions, not corrections to a published page; `prepublication_audit.json` remains separate from`corrections=[]`.

An eligible oral-single comparison, verifiable source data/original registry history, official correction/retraction, or a demonstrated numerical/classification error would trigger revision while preserving any subsequently assigned publicationID/URL. Remaining uncertainties concern the direct effect, paired/crossover-adjustedCI, MCID,some full texts/device details,total intake and long-term safety. They are not clinical research, regrading or translation TODOs passed to the receiver.

**Status:**`completed_with_uncertainty`;content`ready_with_uncertainty`;verification`completed_with_declared_scope`;publication identity`needs_id_assignment`. ID,slug,URL,first publication date and semantic code remain unreservednull. No independent review,journal certification or error-free guarantee is asserted. Technical restoration is separated from clinical judgment. No production-server access,deployment or subsequent task was performed.

## Source identification and access

`sources.json` records exactURLs,DOI/PMID,locations,access,funding and reuse. [S09]is the same study as[S05],and[S14]is the same study as[S13],not independent replication.

- **[S01] Effect of topically applied dexpanthenol on epidermal barrier function and stratum corneum hydration. Results of a human in vivo study**. https://pubmed.ncbi.nlm.nih.gov/10965426/ · DOI 10.1055/s-0031-1300268 · PMID 10965426 · Access: primary_abstract. - **[S02] Efficacy of dexpanthenol in skin protection against irritation: a double-blind, placebo-controlled study**. https://pubmed.ncbi.nlm.nih.gov/14641355/ · DOI 10.1111/j.0105-1873.2003.00184.x · PMID 14641355 · Access: primary_abstract. - **[S03] Skin moisturizing effects of panthenol-based formulations**. https://pubmed.ncbi.nlm.nih.gov/21982351/ · PMID 21982351 · Access: primary_abstract. - **[S04] Efficacy of micronutrient supplementation on skin aging and seasonal variation: a randomized, placebo-controlled, double-blind study**. https://pmc.ncbi.nlm.nih.gov/articles/PMC3832385/ · DOI 10.2147/CIA.S43976 · PMID 24255597 · Access: primary_full_html. - **[S05] Efficacy of a Topical Formulation on Skin Hydration and Barrier Function in Individuals With Xerosis: A 28-Day Randomized, Split-Leg, Untreated-Controlled Trial**. https://onlinelibrary.wiley.com/doi/full/10.1111/jocd.70898 · DOI 10.1111/jocd.70898 · PMID 42108609 · Access: primary_full_text_and_pdf_tables. - **[S06] In vivo efficacy and properties of semisolid formulations containing panthenol**. https://onlinelibrary.wiley.com/doi/10.1111/jocd.12527 · DOI 10.1111/jocd.12527 · Access: primary_publisher_abstract. - **[S07] The Pharmacokinetics of Orally Administered Calcium Pantothenate in Healthy Adults**. https://www.gavinpublishers.com/article/view/the-pharmacokinetics-of-orally-administered-calcium-pantothenate-in-healthy-adults · DOI 10.29011/JVM-106.100006 · Access: exact_current_input_prior_primary_extraction_reused. - **[S08] Pantothenic Acid: Fact Sheet for Health Professionals**. https://ods.od.nih.gov/factsheets/PantothenicAcid-HealthProfessional/ · Access: official_full_html_fresh. - **[S09] Evaluation of Hydrating Cream Effect on Subjects With Dry Skin**. https://clinicaltrials.gov/study/NCT07393191 · Access: official_indexed_record_and_js_shell. - **[S10] Dexpanthenol enhances skin barrier repair and reduces inflammation after sodium lauryl sulphate-induced irritation**. https://pubmed.ncbi.nlm.nih.gov/19753737/ · DOI 10.1080/09546630212345674 · PMID 19753737 · Access: primary_abstract. - **[S11] Maintenance of hand eczema by oral pantothenic acid in a patient sensitized to dexpanthenol**. https://pubmed.ncbi.nlm.nih.gov/9255501/ · DOI 10.1111/j.1600-0536.1997.tb00389.x · PMID 9255501 · Access: primary_index_metadata_only. - **[S12] Tewameter TM 300 measurement principle**. https://www.courage-khazaka.com/en/scientific-products/multi-probe-adapter-basic-systems?catid=16%3Aalle-produkte&id=172%3Atewameter-e&view=article · Access: official_manufacturer_technical_page. - **[S13] Effect of amino-acid intake on physical conditions and skin state: a randomized, double-blind, placebo-controlled, crossover trial**. https://www.jstage.jst.go.jp/article/jcbn/65/1/65_18-108/_article · DOI 10.3164/jcbn.18-108 · PMID 31379414 · Access: primary_full_text_and_pdf_tables. - **[S14] UMIN000017615 trial registration, current version3**. https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000020407 · Access: official_registry_current_version.