Vitamin B12 and acne: eruption signal, treatment benefit unestablished

Useful facts when choosing a product

• S01 used one1-mg intramuscular hydroxocobalamin injection.
• The S01 human product/excipients were not established and are distinct from culture-reagent Sigma.
• The actual dose and molecule of the S03 oral OTC exposure were unreported.
• S04 reports1000 µg/mL as concentration, not an administered dose without volume.

What the research actually shows

# Vitamin B12 and acne: a post-supplementation eruption signal, not established treatment benefit

**TASK-1054 / R01-094 · Evidence cutoff 2026-09-18 · New harm report · Efficacy ungraded · Safety: Caution**

## Thirty-second answer

The searched and accessible evidence did not establish a between-group inflammatory-lesion treatment benefit of single oral B12 in acne patients. Human reports instead describe new acne or acneiform eruptions after supplementation. In the anchor, one of ten people with clear skin developed papules and comedones one week after intramuscular hydroxocobalamin; this is neither population incidence nor randomized causal proof. [S01 pp4–6;S02 Summary;S03 Case/Discussion;S04 Case]

## Original question and scope of this answer

The original question is **“In patients with acne, what effect, difference or risk is associated with vitamin B12 and inflammatory acne lesions?”** The input proposed a single oral product, placebo and a between-group inflammatory-lesion count difference. These were search assumptions, not verified study facts, and remain preserved separately.

The actual anchor concerns **new clinical skin lesions after injection in people with clear skin, not treatment of existing acne**. The therapeutic part is answered as “direct eligible treatment effect not established,” while the risk component is completed from the observations available now. Clinical judgment is not deferred to the recipient.

**One page endpoint:** people developing new facial acne with erythematous papules and comedones. **One page timepoint:** one week after intramuscular hydroxocobalamin. It was selected because human exposure, molecule/route, exposed denominator and onset timing were directly identifiable—not because registered primary status was verified. Day14 gene expression, resampling three months later and withdrawal recovery are not combined into that primary timepoint. [S01 pp4–6,11]

## Verified human evidence table

| Source and access | Actual exposure and population | Clinical outcome and time | Use and limit | |---|---|---|---| | S01 Kang2015, institutional author manuscript | Ten healthy clear-skin participants; one 1-mg IM hydroxocobalamin injection | One developed facial erythematous papules and comedones at one week; lesion counts unreported | Page anchor. No concurrent clinical control or CI; nine without acne over14 days do not establish general safety. [pp4–6,11] | | S02 Veraldi2018, publisher abstract | Five female cases, oral or IM B12; case-specific molecule/dose unverified | Papules/pustules after1 week–5 months; no comedones/cysts; one eosinophilic folliculitis biopsy; all reported to recover3–6 weeks after withdrawal | Supportive harm signal. Five selected cases are not the total exposed denominator. [Summary] | | S03 Bowden2023, publisher full text | Woman aged68, oral OTC B12 weekly for1–2 months; molecule/dose unreported | Papulopustular eruption; doxycycline prescribed while B12 continued; later outcome unreported | Oral case context, not documented withdrawal recovery. [Case;Discussion] | | S04 Karakoç2025, publisher full text | Woman aged26, B12 119 ng/L; IM cyanocobalamin1000 µg/mL daily5 days; volume unreported | Comedone-free eruption in week2; partial improvement2 weeks after withdrawal plus systemic/topical treatments | Deficiency-treatment injection case. Concentration is not dose; co-treatment prevents attribution to withdrawal alone. [pp3–5] | | S05 Ghiasi2018, PubMed abstract | 66 acne patients; isotretinoin+folate+B12 versus isotretinoin,2 months | Blood homocysteine, folate and B12; no lesion-count result in accessed abstract | Excluded as therapeutic anchor: combination and different endpoint. Within-arm P does not establish a between-arm effect. [Abstract] |

## Values that cannot be interchanged

The incident Kang case **had comedones**, whereas the Veraldi and Karakoç eruptions **had no comedones**. Acne vulgaris, post-supplementation monomorphic acneiform eruption, eosinophilic folliculitis, rosacea and allergic rash are therefore not treated as one diagnosis. No worsening rate in existing acne, IGA improvement or total-lesion effect is invented. [S01 p6;S02 Summary;S04 Case]

Healthy participants, confirmed deficiency and isotretinoin-treated acne are different populations. Hydroxocobalamin, cyanocobalamin and unknown-form B12 remain separate. Methylcobalamin was searched, but access-limited evidence was not substituted for oral/injection effects. Topical B12 in atopic dermatitis addresses another question. Blood-marker improvements with combined B vitamins or folate are not evidence that B12 alone treats acne. [S01–S05;access_log.json]

## Self-check of numbers, denominators and statistics

One event among ten exposed is a count of people. The arithmetic receipt verifies 1÷10=0.1 within this sample and 1 mL×1000 µg/mL=1000 µg=1 mg. **Neither is used as population incidence, comparative risk, NNT/NNH or a prescribed dose.** Inferential reanalysis was not performed because a clinical control, representative denominator and clinical effect variance were not available; nonexecution fields contain null and reasons.

The differing S01 day0/day14 RNA-seq denominators reflect library quality. Overlapping healthy subsets and the same nine people resampled three months later were not added as independent participants. Reported adjusted P/AIC criteria and molecular tests were checked but not repurposed as clinical lesion P or CI. In S05, significance within one arm and nonsignificance within another does not show a significant between-arm difference. Nonsignificance is neither equivalence nor exact zero. [S01 pp5,10–13;S05 Abstract]

## Mechanism, limiting observations and access

Microbial gene expression and in-vitro porphyrin support a biological hypothesis, not treatment efficacy, representative incidence or definitive causality. Nine S01 recipients did not develop acne during short observation, and S03 did not supply follow-up after continued B12. Neither “everyone develops a rash” nor “withdrawal always cures it” follows. [S01 pp6,9;S03 Case]

S02 was abstract-only; S05 was also limited to a PubMed abstract. Bahbouhi/Owen/Zubair full texts and some registry details were inaccessible, so snippet numbers were excluded from the verified table. Thirty-four recorded search strings and direct access/failures are retained in search_log.json and access_log.json. Korean/English, molecular forms, treatment/harm, registration, opposing/nonsignificant findings and corrections/retractions were explored, without claiming subscription database searches or an exhaustive systematic review.

## Funding, interests and safety

S01 disclosed two NIH grants and a related patent. S03 declared no support/relevant financial relationships. S04 declared no conflict, but funding remains unverified. S02 funding could not be established from its abstract. The incorrect Veraldi DOI in the S04 reference list was checked against the primary publisher identifier, corrected in the current source record and logged before submission. No relevant official correction/retraction notice was identified in accessed pages/recorded searches; this is not an external clearance certificate. [S01 p1,p14;S02;S03 pp2–3;S04 pp5,7]

Caution. New papules, pustules or another rash after supplementation/injection warrant clinical review of exposure timing, route, actual product and dose, prior skin disease and co-medication. This report is not advice to stop necessary deficiency treatment or select an individual dose. Cobalt hypersensitivity is separate from acne; suspected severe allergic symptoms such as acute breathing difficulty or facial/oral swelling require urgent care. The previously verified NIH absence of an established tolerable upper intake level does not imply unlimited high-dose safety. These data do not establish safety in pregnancy, lactation, children, hepatic/renal disease or long-term co-medication. [S01–S04;reused R89-S05 MHRA, R89-S06 NIH]

## Exact reason no efficacy grade is assigned

This report adopts a safety signal, not a therapeutic efficacy verdict. Section 5 of the supplied common prompt (handoff line94) prohibits forcing safety, interaction or assay-interference questions into the efficacy A–F formula and directs a not_applicable_or_policy_missing / needs_format_mapping report when no suitable mapping is supplied. The original scoring document, “Items that cannot determine the grade,” safety/harm row (line803), separates harm from efficacy grading. Consequently, efficacy grade, score, all seven axes and the numeric anchor are null. This is not automatic non-grading because evidence is observational, nor an F/zero or ? verdict. Human observations exist: no_human_study=false. Memory, depression, ALS, TUG and sleep values are not inherited.

The unchanged original calculator was read and hash-checked, but check_verdict, derive_grade and its CLI were **not executed**. Four decision receipts record nonexecution and capture the complete final report and its SHA. Return, exception, stdout, stderr, exit, error count and numeric anchor are null—not fabricated PASS/zero values. Actual arithmetic and unperformed inferential reanalysis have separate receipts.

## Seven evaluation explanations and seven null-axis reasons

### Claim type · claim_type

null — The original question includes effect, difference and risk; the adopted current finding is a skin-harm signal after B12 exposure. It is not forced into efficacy type B/C, and the exclusion does not mean physical/chemical type A.

### Endpoint · endpoint

null — The observed clinical event is new papules and comedones one week after injection. Lesion reduction and day14 gene expression are not substituted for a clinical therapeutic endpoint. Efficacy H/P/S coding is not applied to this harm report. [S01 pp4–6]

### Replication · replication

null — Overlapping S01 cohorts and selected S02/S03/S04 cases are not independent replications of therapeutic efficacy. Historical review cases were not added, and R1/RX were not invented merely because one observational study was found.

### Independence · independence

null — S01 discloses both NIH funding and a related patent. S03 reports no support/relationships; S04 reports no conflict but funding is unverified; S02 is abstract-only. None is automatically classified as independently funded. [S01 p1,p14;S03 pp2–3;S04 p5]

### Effect size · effect

null — No between-group therapeutic lesion effect or MCID is established. The observed 1/10, dechallenge and mechanism are not converted into effect size, B12 efficacy or population incidence. Harm is not forced into E− to create D/F.

### Bias · bias

null — Nonblinding, absence of a concurrent clinical control, selected cases, co-treatment and reporting limits are described. Efficacy B0/B1/B2 scoring is not applied to this safety report. Nonreporting is not absence of flaws.

### Precision · precision

null — Between-group clinical CI, SD, SE and P are unavailable and were not reanalyzed. They are not filled with C1 or exact zero. Efficacy precision coding is not applied to this harm report.

## Twelve identification facets

**kind** — M — The actual anchor is intramuscular injection, following the injection boundary in supplied multifacet v1 section1. Proposed S remains preserved in the input.

**canonical_entity** — Vitamin B12; hydroxocobalamin in the anchor. Cyanocobalamin and unknown-form cases remain separate evidence rows.

**source_part** — Purified B12 molecule; plant part not applicable. Manufacturing source, organism, batch and purity unverified (U04).

**formulation** — B12 injectable solution; the anchor names hydroxocobalamin. Human product, excipients and complete composition are unreported (U05). Not combined with oral B-complex evidence.

**route** — Intramuscular for the anchor. Oral cases are contextual and do not establish topical, subcutaneous or intravenous effects.

**dose** — S01: one 1-mL injection of 1000 µg/mL; arithmetic conversion 1000 µg=1 mg. Not a personal dose or injection prescription.

**duration** — Single injection; page timepoint one week after injection. Fourteen-day microbial observation and resampling three months later are separate layers.

**population** — Ten healthy people with clear skin, injected for general well-being. Not a therapeutic trial in existing acne; serum B12/deficiency unreported (U03).

**claim** — Signal of new acne/acneiform eruption with inflammatory papules after B12 exposure. Not established therapeutic efficacy or incidence.

**primary_endpoint** — New facial acne with erythematous papules and comedones at one week: one affected person among ten exposed. Not lesion number or a verified registered primary outcome.

**comparator** — Own clear-skin pre-exposure state. No concurrent randomized placebo clinical-event control; later gene comparisons in the same nine people are separate.

**duplicate_key** — internal-only|B12-hydroxocobalamin|IM|clear-skin-healthy|single-1mg|incident-papules-and-comedones|week1|within-person-baseline|harm-report; not a permanent semantic code

## Duplicate checks and reuse

The complete3168-record index and13 original B12 candidates were compared. IDs110,1059,1340,1440,3111,3112,3113,3114,3164,3165,3166,3167,3168 are boundary-reuse records with original IDs, grades/scores, full bilingual texts, sources and uncertainties preserved unchanged. None is the same completed acne claim; this is a new harm report, not skip_duplicate. Completed endpoints were not re-searched, rescored or retranslated. ID3099 concerns B5 acne, a different ingredient. The existing Vitamin B12 hub and original tag are reused; no new hub is created. ID3168 is an ungraded sleep report with null grade/score/seven axes and no_human_study=false, not an acne grade. See intake/duplicate_boundary.json.

## All unresolved and nonapplicable fields

### U01 · Direct therapeutic effect

The searched and accessible material did not establish a between-group inflammatory-lesion treatment effect of single oral B12. This is not worldwide absence of human studies or a zero-effect finding. (not_found_in_searched_scope; value=null)

### U02 · Registered primary endpoint/time

S01 did not establish a registered primary clinical acne endpoint. PRJNA260091 is a sequencing deposit, not trial registration. The page selects the observed one-week event, without claiming prospective primary status. (not_reported; value=null)

### U03 · Baseline deficiency and individual demographics

Serum B12, deficiency classification and individual age/sex distribution of the S01 injection subgroup were not established from the reviewed main manuscript. Healthy clear skin does not establish biochemical sufficiency. (not_reported; value=null)

### U04 · Manufacturing source and total intake

Manufacturing organism/source, batch, purity and total dietary B12 intake were not established for S01. A plant part does not apply to this molecular intervention. (not_reported; value=null)

### U05 · Product and excipients

The human injection brand, manufacturer, excipients and additional components were not reported in S01. Sigma in the culture experiment is not identified as the human injection product. (not_reported; value=null)

### U06 · Concurrent clinical comparator

S01 has no concurrent randomized placebo comparison of clinical events. Resampling nine of the same people without supplementation three months later is a gene-expression control, not an independent clinical 0/9 unexposed group. (not_applicable; value=null)

### U07 · Lesion counts and IGA

Papule/comedone counts, inflammatory/total lesion changes and an IGA change for the incident S01 case were not reported. One affected person is not one lesion. (not_reported; value=null)

### U08 · Clinical effect and uncertainty statistics

Between-group clinical RR, RD, OR, CI, SD, SE and P were not reported. Microbial gene statistics do not replace them. (not_reported; value=null)

### U09 · MCID

No source-verified MCID was established for this event or the unreported lesion-count change. No threshold is invented. (not_reported; value=null)

### U10 · Covariates and background care

Adjusted clinical effects, covariate models and the injection subgroup distribution of medications, skin care, hormonal and dietary factors were not established. Topical treatment in the cross-sectional acne group is not copied to the ten healthy recipients. (not_reported; value=null)

### U11 · Supplement and missingness

Separate S01 supplementary individual clinical follow-up was not retrieved. Day-0 RNA-seq n=7 versus day-14 n=10 concerns library quality, not three clinical dropouts. (inaccessible; value=null)

### U12 · Allocation and blinding

S01 is not a randomized therapeutic efficacy trial and explicitly states that it was not blinded. Successful allocation concealment or double blinding is not claimed. (not_applicable; value=null)

### U13 · Multiplicity detail

S01 specifies adjusted P/AIC criteria for RNA-seq and several molecular tests, but all multiplicity details were not verified against separate supplements. Neither universal nonadjustment nor clinical significance is inferred. (inaccessible; value=null)

### U14 · Injection-case dechallenge/rechallenge

Quantitative dechallenge recovery and rechallenge outcomes for S01 HL414 were not established in the reviewed main paper. Temporality is not randomized causal proof. (not_reported; value=null)

### U15 · Incidence, dose response and long term

Representative exposed denominators, route-specific incidence, dose response and long-term risk were not established. The study fraction 1/10 is not published as a 10% risk for general users. (not_reported; value=null)

### U16 · Exposure detail in five cases

Only the S02 abstract was accessed; case-specific oral/IM route, molecule, dose, formulation, product and deficiency are unverified. Oral and injected exposures are not pooled into a dose effect. (inaccessible; value=null)

### U17 · Funding and selection in five cases

S02 funding, product supply, selection, complete follow-up and rechallenge details cannot be established from the abstract. Independence or consecutive complete ascertainment is not assumed. (inaccessible; value=null)

### U18 · Case denominators

The five S02 cases and one each in S03/S04 are selected cases, not all B12 recipients. They cannot yield population event rates or zero control events. (not_applicable; value=null)

### U19 · Oral OTC form and dose

S03 confirms oral use weekly for 1–2 months; molecule, amount, product and detailed composition are unreported. Oral administration is verified in the Discussion, not inferred solely from OTC status. (not_reported; value=null)

### U20 · Oral-case outcome and deficiency

S03 continued supplementation while prescribing doxycycline. Subsequent recovery, attrition, rechallenge and baseline deficiency values are unreported; this is not a documented cure after withdrawal. (not_reported; value=null)

### U21 · Actual dose in the 2025 case

S04 reports a concentration of 1000 µg/mL. Without injection volume, a 1000-µg dose or 5-mg cumulative five-day exposure cannot be established. (not_reported; value=null)

### U22 · Recovery attribution and co-treatment

S04 combined withdrawal with doxycycline, topical clindamycin/benzoyl peroxide and antihistamines. Partial improvement at two weeks is not complete recovery or a randomized effect of withdrawal alone. (not_applicable; value=null)

### U23 · 2025-case funding and product

S04 declares no conflict, but funding, manufacturer and excipients were not separately established. A conflict declaration does not prove independent funding. (not_reported; value=null)

### U24 · Combination RCT methods

S05 confirms 66 total participants, two groups and two months; per-group allocation/analysis, dose, molecule, route, missingness, registration and funding are unverified. Equal groups of 33 are not assumed. (inaccessible; value=null)

### U25 · Combination RCT lesion outcome

The accessed S05 abstract concerns blood homocysteine, folate and B12, not lesion counts. Significance in one arm and nonsignificance in another does not establish a between-group difference. (not_reported; value=null)

### U26 · Direct methylcobalamin acne evidence

A methylcobalamin ALS experience paper was located but its full text was inaccessible, so acne events and denominators were not directly verified. The completed JETALS muscle-strength verdict was neither re-researched nor repurposed. (inaccessible; value=null)

### U27 · Additional case full texts

Bahbouhi and Owen papers were located and access attempted, but key full texts were unavailable. Patient counts and exposures from snippets were not merged into the verified evidence table. (inaccessible; value=null)

### U28 · Registry and search scope

General web, primary papers, PubMed pages and indexed ClinicalTrials.gov searches were used. Registry detail pages remained loading screens; subscription Embase/Web of Science/CENTRAL database searches were not performed. This is not claimed as an exhaustive systematic review. (not_searched; value=null)

### U29 · Advertising

Advertising claims were not collected for this clinical task. what_ads is null rather than an empty string or invented advertisement. (not_searched; value=null)

### U30 · Permanent identifiers and live publication

New id/site_id/slug/url/semantic code/first publication are null because no allocation or deployment occurred. TASK-1054 is not site 1054. The content-complete report requires only technical format mapping. (not_applicable; value=null)

### U31 · Allergy versus acne

Previously verified cobalt hypersensitivity information concerns a separate hazard. Papules, pustules or comedones do not diagnose allergy, and not every rash is acne vulgaris. (not_applicable; value=null)

### U32 · Safety in special populations

These acne data do not establish safety in pregnancy, lactation, children, hepatic/renal disease or long-term co-medication. Nonreporting is not zero adverse events or confirmed safety. (not_reported; value=null)

### U33 · Historical overlap and citation errors

Earlier same-author S02 cases and review totals may overlap and were not pooled. The Veraldi DOI ending 12325 in S04 conflicts with directly verified 12360; the latter is used. This is not a verified formal erratum. (conflicting; value=null)

### U34 · Correction/retraction completeness

No relevant notice was found on accessed sources and in the recorded title/DOI searches, but all databases and every Crossmark record were not exhaustively checked. (not_searched; value=null)

### U35 · Mechanism as a clinical substitute

S01 gene expression and culture porphyrin are a separate mechanistic layer. Culture concentration is not a human dose and cannot establish lesion treatment efficacy or population incidence. (not_applicable; value=null)

### U36 · Deficiency treatment and prescribing

S04 deficiency treatment at B12 119 ng/L and S01 general-wellbeing injections concern different populations. This signal is not advice to stop necessary deficiency treatment or choose a personal dose. (not_applicable; value=null)

## Advertising and product facts

what_ads=null: advertising was not collected (U29). Product facts are limited to verified sentences: S01 is an intramuscular hydroxocobalamin exposure. S03 is oral OTC but product, dose and molecule are unverified. S04 concentration alone cannot establish an administered dose. No product recommendation or individual prescription is provided.

## Editorial review and actual display paths

This is a completed, as-of-date report researched, source-checked and editorially self-reviewed by the same assistant in this conversation. It is not independent external review, journal certification, diagnosis or prescribing. Document quality A is a self-assessment of source traceability, boundaries, uncertainty, bilingual completeness and format—not efficacy A or an error-free guarantee. Initial public corrections=[]; pre-submission changes are retained separately in audit.

editorial_review version1.0 / ready_with_uncertainty / independent=false. Result: completed_with_uncertainty; publication: needs_format_mapping; grading_status=not_applicable_or_policy_missing. New ID, slug, URL, semantic code and first publication are null; clinical_todo=[]. The report’s en.body_markdown and en.what_research equal the full publication.en.md UTF8 bytes; the same equality holds for both Korean fields and publication.ko.md. These are actual local display originals; no live site URL has been assigned. No clinical research, rescoring, calculator or statistics rerun is requested from the recipient.

## Sources and locations

**[S01] Kang D, Shi B, Erfe MC, Craft N, Li H. Vitamin B12 modulates the transcriptome of the skin microbiota in acne pathogenesis.** Sci Transl Med. 2015;7(293):293ra103. doi: 10.1126/scitranslmed.aab2009; pmid: 26109103; pmcid: PMC6049814. institutional_author_manuscript_full_text. PDF p1: bibliographic record, competing interests and sequence data; PDF pp4–6: longitudinal exposure and clinical incident event; PDF pp9–11: limitations, population and exposure methods; PDF p13: statistical methods; p14: funding. [Primary source](https://escholarship.org/content/qt3bv7t1nw/qt3bv7t1nw.pdf).

**[S02] Veraldi S, Benardon S, Diani M, Barbareschi M. Acneiform eruptions caused by vitamin B12: A report of five cases and review of the literature.** J Cosmet Dermatol. 2018;17(1):112–115; online 2017-06-08. doi: 10.1111/jocd.12360; pmid: 28594082. publisher_abstract_only. Publisher Summary; header publication dates; References. [Primary source](https://onlinelibrary.wiley.com/doi/10.1111/jocd.12360).

**[S03] Bowden A, Ekeh O, Brownstone ND, Hsu S. Acneiform Eruption Secondary to Over-the-Counter Vitamin B12.** Cureus. 2023;15(8):e43275. doi: 10.7759/cureus.43275; pmcid: PMC10492573. publisher_full_text_PDF. PDF p1: case presentation; PDF p2: discussion confirms oral use and disclosures; PDF p3: references. [Primary source](https://www.cureus.com/articles/178225-acneiform-eruption-secondary-to-over-the-counter-vitamin-b12.pdf).

**[S04] Karakoç Y, Yıldız N, Aksoy H, Fidancı İ, Ayhan Başer D. A rare aspect of commonly administered vitamin B12 injection therapy in primary care: Acneiform eruption.** Ankara Med J. 2025;25(4):467–472. doi: 10.5505/amj.2025.82258. publisher_full_text_PDF. PDF cover: issue/DOI and submission/acceptance dates; PDF pp3–4 (printed468–469): case, concentration, exposure and follow-up; PDF p5: partial regression figure and conflict statement; PDF p7: references. [Primary source](https://jag.journalagent.com/z4/download_fulltext.asp?pdir=amj&plng=eng&un=AMJ-82258).

**[S05] Ghiasi M, Mortazavi H, Jafari M. Efficacy of Folic Acid and Vitamin B12 Replacement Therapies in the Reduction of Adverse Effects of Isotretinoin: A Randomized Controlled Trial.** Skinmed. 2018;16(4):239–245. pmid: 30207526. PubMed_primary_abstract_only. PubMed bibliographic header and Abstract. [Primary source](https://pubmed.ncbi.nlm.nih.gov/30207526/).

**[R89-S05] MHRA. Vitamin B12 (hydroxocobalamin, cyanocobalamin): known cobalt allergy and sensitivity reactions. 18 December 2023.** [Source](https://www.gov.uk/drug-safety-update/vitamin-b12-hydroxocobalamin-cyanocobalamin-advise-patients-with-known-cobalt-allergy-to-be-vigilant-for-sensitivity-reactions). Reused original R01-089 extraction; not newly browsed for this task.

**[R89-S06] NIH ODS. Vitamin B12 Health Professional Fact Sheet.** [Source](https://ods.od.nih.gov/factsheets/VitaminB12-HealthProfessional/). Reused original R01-089 extraction; not newly browsed for this task.

Why this is classified as Unscored

This report adopts a safety signal, not a therapeutic efficacy verdict. Section 5 of the supplied common prompt (handoff line94) prohibits forcing safety, interaction or assay-interference questions into the efficacy A–F formula and directs a not_applicable_or_policy_missing / needs_format_mapping report when no suitable mapping is supplied. The original scoring document, “Items that cannot determine the grade,” safety/harm row (line803), separates harm from efficacy grading. Consequently, efficacy grade, score, all seven axes and the numeric anchor are null. This is not automatic non-grading because evidence is observational, nor an F/zero or ? verdict. Human observations exist: no_human_study=false. Memory, depression, ALS, TUG and sleep values are not inherited.

Counterpoint. null — No between-group therapeutic lesion effect or MCID is established. The observed 1/10, dechallenge and mechanism are not converted into effect size, B12 efficacy or population incidence. Harm is not forced into E− to create D/F.

Rejudgment record. not_applicable_or_policy_missing — This report adopts a safety signal, not a therapeutic efficacy verdict. Section 5 of the supplied common prompt (handoff line94) prohibits forcing safety, interaction or assay-interference questions into the efficacy A–F formula and directs a not_applicable_or_policy_missing / needs_format_mapping report when no suitable mapping is supplied. The original scoring document, “Items that cannot determine the grade,” safety/harm row (line803), separates harm from efficacy grading. Consequently, efficacy grade, score, all seven axes and the numeric anchor are null. This is not automatic non-grading because evidence is observational, nor an F/zero or ? verdict. Human observations exist: no_human_study=false. Memory, depression, ALS, TUG and sleep values are not inherited.

Review performed and remaining limitations

[{'id': 'U01', 'label': 'Direct therapeutic effect', 'status': 'not_found_in_searched_scope', 'value': None, 'reason': 'The searched and accessible material did not establish a between-group inflammatory-lesion treatment effect of single oral B12. This is not worldwide absence of human studies or a zero-effect finding.'}, {'id': 'U02', 'label': 'Registered primary endpoint/time', 'status': 'not_reported', 'value': None, 'reason': 'S01 did not establish a registered primary clinical acne endpoint. PRJNA260091 is a sequencing deposit, not trial registration. The page selects the observed one-week event, without claiming prospective primary status.'}, {'id': 'U03', 'label': 'Baseline deficiency and individual demographics', 'status': 'not_reported', 'value': None, 'reason': 'Serum B12, deficiency classification and individual age/sex distribution of the S01 injection subgroup were not established from the reviewed main manuscript. Healthy clear skin does not establish biochemical sufficiency.'}, {'id': 'U04', 'label': 'Manufacturing source and total intake', 'status': 'not_reported', 'value': None, 'reason': 'Manufacturing organism/source, batch, purity and total dietary B12 intake were not established for S01. A plant part does not apply to this molecular intervention.'}, {'id': 'U05', 'label': 'Product and excipients', 'status': 'not_reported', 'value': None, 'reason': 'The human injection brand, manufacturer, excipients and additional components were not reported in S01. Sigma in the culture experiment is not identified as the human injection product.'}, {'id': 'U06', 'label': 'Concurrent clinical comparator', 'status': 'not_applicable', 'value': None, 'reason': 'S01 has no concurrent randomized placebo comparison of clinical events. Resampling nine of the same people without supplementation three months later is a gene-expression control, not an independent clinical 0/9 unexposed group.'}, {'id': 'U07', 'label': 'Lesion counts and IGA', 'status': 'not_reported', 'value': None, 'reason': 'Papule/comedone counts, inflammatory/total lesion changes and an IGA change for the incident S01 case were not reported. One affected person is not one lesion.'}, {'id': 'U08', 'label': 'Clinical effect and uncertainty statistics', 'status': 'not_reported', 'value': None, 'reason': 'Between-group clinical RR, RD, OR, CI, SD, SE and P were not reported. Microbial gene statistics do not replace them.'}, {'id': 'U09', 'label': 'MCID', 'status': 'not_reported', 'value': None, 'reason': 'No source-verified MCID was established for this event or the unreported lesion-count change. No threshold is invented.'}, {'id': 'U10', 'label': 'Covariates and background care', 'status': 'not_reported', 'value': None, 'reason': 'Adjusted clinical effects, covariate models and the injection subgroup distribution of medications, skin care, hormonal and dietary factors were not established. Topical treatment in the cross-sectional acne group is not copied to the ten healthy recipients.'}, {'id': 'U11', 'label': 'Supplement and missingness', 'status': 'inaccessible', 'value': None, 'reason': 'Separate S01 supplementary individual clinical follow-up was not retrieved. Day-0 RNA-seq n=7 versus day-14 n=10 concerns library quality, not three clinical dropouts.'}, {'id': 'U12', 'label': 'Allocation and blinding', 'status': 'not_applicable', 'value': None, 'reason': 'S01 is not a randomized therapeutic efficacy trial and explicitly states that it was not blinded. Successful allocation concealment or double blinding is not claimed.'}, {'id': 'U13', 'label': 'Multiplicity detail', 'status': 'inaccessible', 'value': None, 'reason': 'S01 specifies adjusted P/AIC criteria for RNA-seq and several molecular tests, but all multiplicity details were not verified against separate supplements. Neither universal nonadjustment nor clinical significance is inferred.'}, {'id': 'U14', 'label': 'Injection-case dechallenge/rechallenge', 'status': 'not_reported', 'value': None, 'reason': 'Quantitative dechallenge recovery and rechallenge outcomes for S01 HL414 were not established in the reviewed main paper. Temporality is not randomized causal proof.'}, {'id': 'U15', 'label': 'Incidence, dose response and long term', 'status': 'not_reported', 'value': None, 'reason': 'Representative exposed denominators, route-specific incidence, dose response and long-term risk were not established. The study fraction 1/10 is not published as a 10% risk for general users.'}, {'id': 'U16', 'label': 'Exposure detail in five cases', 'status': 'inaccessible', 'value': None, 'reason': 'Only the S02 abstract was accessed; case-specific oral/IM route, molecule, dose, formulation, product and deficiency are unverified. Oral and injected exposures are not pooled into a dose effect.'}, {'id': 'U17', 'label': 'Funding and selection in five cases', 'status': 'inaccessible', 'value': None, 'reason': 'S02 funding, product supply, selection, complete follow-up and rechallenge details cannot be established from the abstract. Independence or consecutive complete ascertainment is not assumed.'}, {'id': 'U18', 'label': 'Case denominators', 'status': 'not_applicable', 'value': None, 'reason': 'The five S02 cases and one each in S03/S04 are selected cases, not all B12 recipients. They cannot yield population event rates or zero control events.'}, {'id': 'U19', 'label': 'Oral OTC form and dose', 'status': 'not_reported', 'value': None, 'reason': 'S03 confirms oral use weekly for 1–2 months; molecule, amount, product and detailed composition are unreported. Oral administration is verified in the Discussion, not inferred solely from OTC status.'}, {'id': 'U20', 'label': 'Oral-case outcome and deficiency', 'status': 'not_reported', 'value': None, 'reason': 'S03 continued supplementation while prescribing doxycycline. Subsequent recovery, attrition, rechallenge and baseline deficiency values are unreported; this is not a documented cure after withdrawal.'}, {'id': 'U21', 'label': 'Actual dose in the 2025 case', 'status': 'not_reported', 'value': None, 'reason': 'S04 reports a concentration of 1000 µg/mL. Without injection volume, a 1000-µg dose or 5-mg cumulative five-day exposure cannot be established.'}, {'id': 'U22', 'label': 'Recovery attribution and co-treatment', 'status': 'not_applicable', 'value': None, 'reason': 'S04 combined withdrawal with doxycycline, topical clindamycin/benzoyl peroxide and antihistamines. Partial improvement at two weeks is not complete recovery or a randomized effect of withdrawal alone.'}, {'id': 'U23', 'label': '2025-case funding and product', 'status': 'not_reported', 'value': None, 'reason': 'S04 declares no conflict, but funding, manufacturer and excipients were not separately established. A conflict declaration does not prove independent funding.'}, {'id': 'U24', 'label': 'Combination RCT methods', 'status': 'inaccessible', 'value': None, 'reason': 'S05 confirms 66 total participants, two groups and two months; per-group allocation/analysis, dose, molecule, route, missingness, registration and funding are unverified. Equal groups of 33 are not assumed.'}, {'id': 'U25', 'label': 'Combination RCT lesion outcome', 'status': 'not_reported', 'value': None, 'reason': 'The accessed S05 abstract concerns blood homocysteine, folate and B12, not lesion counts. Significance in one arm and nonsignificance in another does not establish a between-group difference.'}, {'id': 'U26', 'label': 'Direct methylcobalamin acne evidence', 'status': 'inaccessible', 'value': None, 'reason': 'A methylcobalamin ALS experience paper was located but its full text was inaccessible, so acne events and denominators were not directly verified. The completed JETALS muscle-strength verdict was neither re-researched nor repurposed.'}, {'id': 'U27', 'label': 'Additional case full texts', 'status': 'inaccessible', 'value': None, 'reason': 'Bahbouhi and Owen papers were located and access attempted, but key full texts were unavailable. Patient counts and exposures from snippets were not merged into the verified evidence table.'}, {'id': 'U28', 'label': 'Registry and search scope', 'status': 'not_searched', 'value': None, 'reason': 'General web, primary papers, PubMed pages and indexed ClinicalTrials.gov searches were used. Registry detail pages remained loading screens; subscription Embase/Web of Science/CENTRAL database searches were not performed. This is not claimed as an exhaustive systematic review.'}, {'id': 'U29', 'label': 'Advertising', 'status': 'not_searched', 'value': None, 'reason': 'Advertising claims were not collected for this clinical task. what_ads is null rather than an empty string or invented advertisement.'}, {'id': 'U30', 'label': 'Permanent identifiers and live publication', 'status': 'not_applicable', 'value': None, 'reason': 'New id/site_id/slug/url/semantic code/first publication are null because no allocation or deployment occurred. TASK-1054 is not site 1054. The content-complete report requires only technical format mapping.'}, {'id': 'U31', 'label': 'Allergy versus acne', 'status': 'not_applicable', 'value': None, 'reason': 'Previously verified cobalt hypersensitivity information concerns a separate hazard. Papules, pustules or comedones do not diagnose allergy, and not every rash is acne vulgaris.'}, {'id': 'U32', 'label': 'Safety in special populations', 'status': 'not_reported', 'value': None, 'reason': 'These acne data do not establish safety in pregnancy, lactation, children, hepatic/renal disease or long-term co-medication. Nonreporting is not zero adverse events or confirmed safety.'}, {'id': 'U33', 'label': 'Historical overlap and citation errors', 'status': 'conflicting', 'value': None, 'reason': 'Earlier same-author S02 cases and review totals may overlap and were not pooled. The Veraldi DOI ending 12325 in S04 conflicts with directly verified 12360; the latter is used. This is not a verified formal erratum.'}, {'id': 'U34', 'label': 'Correction/retraction completeness', 'status': 'not_searched', 'value': None, 'reason': 'No relevant notice was found on accessed sources and in the recorded title/DOI searches, but all databases and every Crossmark record were not exhaustively checked.'}, {'id': 'U35', 'label': 'Mechanism as a clinical substitute', 'status': 'not_applicable', 'value': None, 'reason': 'S01 gene expression and culture porphyrin are a separate mechanistic layer. Culture concentration is not a human dose and cannot establish lesion treatment efficacy or population incidence.'}, {'id': 'U36', 'label': 'Deficiency treatment and prescribing', 'status': 'not_applicable', 'value': None, 'reason': 'S04 deficiency treatment at B12 119 ng/L and S01 general-wellbeing injections concern different populations. This signal is not advice to stop necessary deficiency treatment or choose a personal dose.'}]

Evidence Table

| Source and access | Actual exposure and population | Clinical outcome and time | Use and limit | |---|---|---|---| | S01 Kang2015, institutional author manuscript | Ten healthy clear-skin participants; one 1-mg IM hydroxocobalamin injection | One developed facial erythematous papules and comedones at one week; lesion counts unreported | Page anchor. No concurrent clinical control or CI; nine without acne over14 days do not establish general safety. [pp4–6,11] | | S02 Veraldi2018, publisher abstract | Five female cases, oral or IM B12; case-specific molecule/dose unverified | Papules/pustules after1 week–5 months; no comedones/cysts; one eosinophilic folliculitis biopsy; all reported to recover3–6 weeks after withdrawal | Supportive harm signal. Five selected cases are not the total exposed denominator. [Summary] | | S03 Bowden2023, publisher full text | Woman aged68, oral OTC B12 weekly for1–2 months; molecule/dose unreported | Papulopustular eruption; doxycycline prescribed while B12 continued; later outcome unreported | Oral case context, not documented withdrawal recovery. [Case;Discussion] | | S04 Karakoç2025, publisher full text | Woman aged26, B12 119 ng/L; IM cyanocobalamin1000 µg/mL daily5 days; volume unreported | Comedone-free eruption in week2; partial improvement2 weeks after withdrawal plus systemic/topical treatments | Deficiency-treatment injection case. Concentration is not dose; co-treatment prevents attribution to withdrawal alone. [pp3–5] | | S05 Ghiasi2018, PubMed abstract | 66 acne patients; isotretinoin+folate+B12 versus isotretinoin,2 months | Blood homocysteine, folate and B12; no lesion-count result in accessed abstract | Excluded as therapeutic anchor: combination and different endpoint. Within-arm P does not establish a between-arm effect. [Abstract] |

Receipt — 7 References

Evidence access cutoff: 2026-09-18. Each citation states its actual access level (full-text transcription, abstract, index, or other) and remaining limitations. Bibliographic checking does not certify the study results or treatment efficacy.

What this document does and does not do

Chamgap is an information source. It reports what research has and has not confirmed; it does not tell readers what to take or buy. That decision belongs to readers and, when needed, medical or legal professionals. This verdict reflects literature available up to the search date and may change as new research appears. Nothing here is medical advice.