Sole added folic acid and MCI cognition: a limited signal in twelve-month WAIS-RC Full Scale IQ

Useful facts when choosing a product

• S01 reports an oral folic acid 400-microgram tablet, one tablet daily, with medicinal permit H10970079.
• The reported manufacturer is Beijing Scrianen Pharmaceutical Co., Ltd., China; this does not verify a current approved MCI indication.
• Salt, manufacturing origin, release profile, excipients, purity, lot, total dietary intake and product-supply contracts are unverified.

What the research actually shows

# Sole added folic acid × twelve-month global cognitive performance in MCI

TASK-1044 / R01-084 · New independent claim · Evidence cutoff 2026-09-17T21:31:13+09:00

## Thirty-second answer

In one trial family of Chinese adults aged at least 65 with study-diagnosed mild cognitive impairment (MCI), adding **oral folic acid 400 micrograms/day (0.4 mg/day) to conventional non-pharmacological and dietary care** produced a small reported signal on **Chinese WAIS-RC Full Scale IQ at twelve months** (d=0.153, P=0.028). Blinding, sample-size and numerical/analysis-reporting concerns prevent concluding that meaningful everyday cognitive benefit is established. A raw-IQ contrast and valid confidence interval were not adopted as verified; that is not a finding of zero effect or equivalence. [S01]

**Current efficacy C / 50; safety Caution.** Grade C is the actual original-calculator result; 50 is a separate fixed anchor. Manuscript quality A concerns completeness of sourcing, limitations, bilingual content and structure, not efficacy grade A, independent external review or journal certification.

## Planned question and selected actual boundary

MoCA was a planned question, not an observed fact. The direct paper used WAIS-RC, so **one endpoint, Full Scale IQ, and one time point, twelve months**, were selected. Favorable Information or Digit Span subtests were not substituted for the broad score. The fully accessible 400-microgram/conventional-care report anchors the page; the 2024 800-microgram/placebo report remains adjacent evidence. This does not hide newer evidence or imply that 400 micrograms is an optimal dose. The paper’s main outcome is separate from a registry-designated primary outcome; registry detail/history could not be verified. [S01, S05, S09]

The paper identifies folic-acid tablets, medicinal permit H10970079 and Beijing Scrianen Pharmaceutical. The actual trial formulation is therefore classified as kind M under the supplied taxonomy rather than forcing the provisional nutritional-supplement S code. This does not verify a current Chinese or Korean cognitive indication. Folic acid is the sole randomized added active ingredient, not a B6/B12/DHA combination. Manufacturing origin, salt, crystalline form, release profile, excipients and purity remain null. [S01; supplied multifacet classification v1]

The comparator is not placebo: both groups received conventional non-pharmacological memory/lifestyle and dietary advice, with no added folic-acid tablet in controls. The memory guidance booklet is identified, but full drug-by-drug background balance is not verified. Folic acid, 5-MTHF, folinic acid, dietary/fortified folate and B-vitamin/DHA combinations are not merged. The claim is not generalized to healthy adults, subjective complaints alone, dementia/Alzheimer disease, vascular impairment, depression/delirium, special diseases or confirmed-deficiency treatment. [S01]

## Participants and baseline nutrition

This was an individually randomized parallel trial after community sampling. Cluster community sampling is not cluster randomization. The paper reports enrollment in March–April 2013 and registration on 2013-05-04, so prospective confirmatory registration is not certified. Screening eligibility differs between Results (2,293) and Methods (2,317); this inconsistency is preserved. [S01]

The modified-Petersen definition includes memory complaints lasting at least two weeks, objective performance at least 1.5 SD below age/education norms on the MMSE memory subtask, preserved daily activities (ADL<26) and exclusion of dementia. Its general-cognition criterion is internally contradictory, describing normal cognition and a deficit of more than 1.5 SD together. The fact that the study reports diagnosed MCI and the diagnostic ambiguity are both retained. Formal amnestic/non-amnestic or single/multidomain subclassification and biomarker-positive MCI due to Alzheimer disease are unverified. Major psychiatric conditions were excluded, but completeness of every differential diagnosis is not certified. [S01]

Table 1 reports, folic-acid/control respectively, mean age 73.71/73.52 years, education 9.14/9.81 years, MMSE 25.60/26.13, serum folate 7.01/6.33 ng/mL and B12 571.25/568.48 pg/mL. These are baseline descriptors, not the selected endpoint. Hcy 13.65/12.19 is printed with mmol/L; it is not silently changed to the more familiar micromole unit. Table 2 labels the same baseline Hcy values as μmol/L and lists control baseline folate as 5.79±2.67 ng/mL, versus 6.33±0.97 in Table 1. These are explicit cross-table unit/value conflicts; neither table is silently designated the correction. [S01, Tables 1/2]

The B12 subgroup boundary of 569.24 pg/mL is a median split, not a deficiency threshold. The paper separately mentions three participants below 200 pg/mL, two in the folic-acid group and one control. Thus, all participants are not labeled B12-replete. Individual confirmed folate-deficiency status, total dietary/fortified/supplement exposure and renal function were not established. A non-fortified setting does not diagnose deficiency in every individual. [S01]

## Scale, time and denominators

WAIS-RC is the Chinese revised Wechsler Adult Intelligence Scale. Methods describes eleven subtests and IQ/index scores calculated using Chinese age norms, whereas Table 3 lists twelve subtest rows including Digit Symbol in addition to Full Scale IQ. This instrument-composition discrepancy remains unresolved. Trained physicians administered testing at baseline, six and twelve months, with higher cognitive scores treated as improvement. Effective raw-IQ limits, an additional education-point correction and version-specific reliability coefficients were not verified. A 0–30 MoCA/MMSE range or MoCA one-point education correction was not inserted. [S01]

Randomization was 84/84=168, completion 77/75=152 and loss 7/9. Printed table n=84/84 is distinct from the completer denominators. ITT with last observation carried forward and available-observation mixed models under missing-at-random assumptions are both described, leaving outcome-specific handling and analysis denominators uncertain. Completion percentage is not pill adherence. Fifteen telephone contacts and blood monitoring are reported, but the actual proportion of tablets taken is not. [S01]

## Numerical audit: reports versus calculations

| Item | Folic acid | Control | Interpretation | |---|---:|---:|---| | Table 3 baseline Full Scale IQ Z | −1.10 ± 0.95 | −0.87 ± 0.90 | Z standardized across visits, not raw IQ points | | Six-month Full Scale IQ Z | 0.25 ± 0.09 | 0.11 ± 0.18 | Not the selected time point | | Twelve-month Full Scale IQ Z | 0.85 ± 1.04 | 0.16 ± 0.61 | The SD/SE identity of ± was not verified for Table 3 itself | | Arithmetic baseline-to-twelve-month change | +1.95 Z | +1.03 Z | Within-group descriptive changes, not treatment effects by themselves | | Unadjusted arithmetic change contrast | +0.92 Z | — | Not adopted as an official baseline-adjusted raw-IQ effect |

The repeated ANCOVA interaction is reported as P=0.044, partial eta-squared=0.082; the mixed-model standardized effect is d=0.153, P=0.028. These are not treated as the same analysis or unit. Table 5’s twelve-month FA-by-wave row reports coefficient 0.512, SE 0.243, t=2.503, P=0.027 and 95% CI 0.074–1.145. Actual division gives 0.512/0.243=2.106996, while a simple normal-Wald interval is 0.03572–0.98828. No original number was silently corrected. The discrepancy requires model/reporting clarification, and the mapping to raw-IQ units is also insufficient. [S01, Tables 3/5; numeric_calculation_receipt.json]

Assuming Table 3’s ± values were SDs permits a conditional unadjusted final-score SMD, but the dispersion assumption is unverified and the result is not the selected baseline-adjusted mixed-model estimand; it is not adopted. A diagnostic conversion of the repeated-model t as though it were an independent two-arm t was also executed and rejected for its inappropriate design assumption. Reported d=0.153 is preserved without claiming independent reproduction of its derivation. No event-based ARR/NNT, borrowed scale MCID or zero effect was manufactured.

## How much benefit?

Supplied Case 28 directs statistical magnitude classification when a validated between-group MCID is unavailable. Reported d=0.153 is below 0.2, so **E~ is adopted only as a classification of the small reported statistical magnitude**. The old calculator’s below-MCID label is not allowed to imply an actual validated clinical threshold; axis notes and receipts state the difference. Uncertainty in the derivation of d and conflicting numerical reporting inform B2/CX and the limited conclusion. Existing numbers are not relabeled as wholly unreported EX or absence of human research.

A change in Full Scale IQ performance is not established benefit in every memory, attention, executive or learning domain, daily functioning, dementia conversion or quality of life. Positive Information/Digit Span findings and non-significant results on other tests remain different endpoints. Non-significance is not equivalence. Folate, Hcy, inflammatory and amyloid biomarkers do not replace the between-group cognitive effect. A separate estimate of repeated-testing practice effects was not reported. [S01]

## Contrary/adjacent evidence and overlapping families

Six-, twelve- and twenty-four-month reports are grouped under ChiCTR-TRC-13003227. The six/twenty-four-month reports use 180 participants and the twelve-month report 168; unresolved participant reconciliation precludes summation. A separate 2019 four-arm, 240-person study contains a sole-folic-acid arm, but its abstract’s combination d=0.169 was not borrowed. A 2024 four-arm, 280-person study reports sole folic acid 800 micrograms/day versus placebo at twelve months, Full Scale IQ beta=1.992 (95% CI 1.304–2.679, P<0.001). Full-text modeling, dispersion, missingness and family independence are unverified, and the dose/comparator differ; this is not pooled with the selected 400-microgram estimate. [S02–S05]

The 2021 Bai paper, DOI 10.3233/JAD-200997, was excluded from efficacy support following the formal 2023-04-25 retraction. The notice concerns ethical approval and trial registration and discusses clarifying independence from earlier work during possible re-review. It is not rewritten as proven fabrication or retraction of every related report. [S06–S07]

Existing record 486’s combined B6/B12/folate prevention, homocysteine and atrophy evidence provides an exclusion map, not an exact duplicate of this sole-folic-acid MCI comparison. The stroke, hemoglobin, MDD, sperm and SBP judgments of 3107, 3108, 3109, 3110 and 3159 were not transferred. Search consisted of supplied-material reuse and targeted public-web gap filling, not exhaustive searching of every subscription database. Irrelevant results or access failures do not imply no human research exists.

## Bias, funding and safety

Actual risks include the decisive n=168 small trial and the no-placebo/unverified-blinding design. Methods and discussion conflict about participant blinding; assessor blinding and allocation concealment are not certified. Bonferroni post-hoc testing is mentioned, but one prospective multiplicity family across every cognitive and blood outcome is not established. Failure of a registry-primary endpoint is null, not invented for downgrading. Public NSFC funding 81130053 and the no-financial-competing-interests declaration were read, supporting I2 within the disclosed-funding scope; all product provision/contracts were not verified. [S01, S09]

The safety label is **Caution**. Qualitative infrequency of adverse events does not establish AE/SAE=0 in either arm or long-term safety. B12-deficiency masking with continuing neurological damage and anticonvulsant interaction context were verified in official information for a different 5-mg product. That product’s excipients, event frequencies, doses and indication are not transferred to the 400-microgram trial product. Research doses are not personal dosing recommendations, prescription-change or discontinuation instructions, or a substitute for standard care. [S08]

## Assessment and completion scope

The actual axes B/P/R1/I2/E~/B2/CX were entered into the unchanged supplied calculator’s validate_axes, derive_grade and check_verdict functions and its one-record CLI. Grade C and the separate one-I2-strength anchor of 50 are documented in four assessment receipts. Manuscript quality A is self-assessed; there was no independent external review.

Content is completed_with_uncertainty with editorial ready_with_uncertainty and an empty clinical TODO array. Technical ID, slug, URL, semantic code and first-publication timestamp remain null with needs_id_assignment. Prior 79–83 FULL5/5 belongs to the closed previous chat, not the new chat’s FULL0/5. This delivery completes research and local transport testing, not production build, server access or deployment. Task 85 was not started.

## Unverified values and revision conditions

The nulls below are current evidence limits, not an unfinished manuscript. New independent homogeneous trials, corrections/retractions, original registration/analysis code/individual data, reliable d/raw-IQ effects and CIs, a validated between-group MCID, or changed diagnostic/nutritional/safety boundaries may trigger revision. No mandatory clinical re-search, regrading or calculator rerun is transferred as a TODO in this handoff.

| Field | Value/status | Reason | |---|---|---| | `formal_MCI_subtype` | null / not_reported | Formal amnestic/non-amnestic and single/multidomain subclassification was not reported. | | `registered_primary_outcome` | null / inaccessible | Registry-detail retrieval failed. The paper’s main outcome is not relabeled as registry-primary. | | `raw_IQ_scale_limits` | null / not_reported | The effective minimum/maximum raw IQ range for the administered standardization was not verified. MoCA/MMSE 0–30 is not substituted. | | `education_score_correction` | null / not_reported | Age/education norms inform diagnosis and Chinese age norms inform IQ; an additional point-based educational correction is unverified. | | `MCID` | null / not_reported | No verified between-group MCID for this comparison was identified in the accessed sources; no threshold from another scale or individual response was borrowed. | | `verified_raw_IQ_effect` | null / conflicting | Internal coefficient/SE/t/CI inconsistencies and limited unit documentation prevent adopting a verified raw-IQ effect. | | `d_recalculated_from_original_model` | null / conflicting | The original numerator, raw whole-sample baseline SD and repeated-model details are insufficient, with conflicting adjacent coefficient reporting. d=0.153 is adopted only as a reported value. | | `total_folate_intake` | null / not_reported | Actual combined intake from diet, fortification and other supplements was not reported. | | `folate_deficiency_count` | null / not_reported | Individual confirmed folate-deficiency counts and trial-specific thresholds were not verified. Mean concentrations do not classify everyone as deficient or replete. | | `renal_function` | null / not_reported | Baseline eGFR/creatinine and renal-subgroup effects were not reported. | | `salt_origin_release_excipients` | null / not_reported | The molecule is reported as folic acid, but salt, manufacturing origin, release profile and excipients are unverified. | | `co_medication_balance` | null / not_reported | Medication-list collection was reported, but actual drug-specific concomitant distributions and rescue therapy were not verified. | | `pill_adherence_percent` | null / not_reported | Fifteen telephone contacts and blood monitoring were reported, but actual pill adherence was not. Completion is not adherence. | | `AE_SAE_discontinuation_counts` | null / not_reported | Only qualitative infrequency is described; arm-specific unique-patient AE/SAE and adverse-event discontinuation counts/denominators are unverified. | | `long_term_special_population_safety` | null / not_reported | The selected trial does not establish long-term, pregnancy, pediatric or hepatic/renal-disease safety. | | `assay_interference` | null / not_reported | Actual assay-interference events or assessment were not verified in the selected trial. | | `allocation_concealment` | null / not_reported | Computer sequence generation is reported; implementation of central allocation, opaque envelopes or other concealment was not verified. | | `blinding` | null / conflicting | The discussion describes unaware participants whereas methods say patient blinding was infeasible. Assessor blinding is not certified. | | `missing_data_model` | null / conflicting | ITT/LOCF and available-observation MAR mixed models are both described; outcome-specific handling and denominators are unclear. | | `practice_effect_size` | null / not_reported | No separate estimate of practice effects was reported. Common repeated testing does not establish elimination of expectancy or assessment bias. | | `product_contracts` | null / not_reported | Beyond public funding and the no-financial-COI declaration, free product provision and contract details are unverified. | | `participant_overlap_2024_retracted_family` | null / inaccessible | Full 2024 registration/text and participant links to the retracted 2021 family were not verified. Neither identity nor independence is asserted. |

## Expert evidence table: seven rows, not seven independent trials

### S01 · Ma 2016 · FAM-13003227

**Design:** Individually randomized, two parallel arms; cluster community sampling is not cluster randomization. No placebo; conflicting blinding descriptions.

**Denominators:** Randomized 84/84=168; completed 77/75=152; lost 7/9. Printed table n=84/84 is not a completer denominator.

**Funding:** Public NSFC grant 81130053 and declaration of no financial competing interests read directly. Product provision/contracts unverified.

**Endpoint:** Twelve-month WAIS-RC Full Scale IQ; visit Z scores, repeated-model coefficients and reported d remain separate.

**Result:** Reported d=0.153, P=0.028. The month-12 row, 0.512/SE0.243/t2.503/P0.027/CI0.074–1.145, has arithmetic concerns and is not adopted as a verified raw-IQ difference.

**Weight:** One direct trial family for the selected 400-microgram/conventional-care/twelve-month comparison. A small reported signal, not established clinical benefit.

### S02/S03 · same registered family, 6/24 months

**Design:** Linked through ChiCTR-TRC-13003227; primary abstracts accessed.

**Denominators:** Reports use 180 participants; the 24-month report uses 90/90. Person-level reconciliation with the 168-person report is unverified.

**Funding:** Separate product contracts were not verified. Shared investigators and registration do not constitute independent replication.

**Endpoint:** Six- and twenty-four-month WAIS-RC, separate from the selected twelve-month endpoint.

**Result:** Six-month reported d=0.168, P=0.031; positive wording in the 24-month abstract is not an exact twelve-month effect.

**Weight:** Longitudinal context only; no increase in the independent-trial count.

### S04 · Ma 2019, four B12-related arms

**Design:** Sole folic acid, sole B12, combination, and no-treatment groups for six months; reported single blinding.

**Denominators:** 240 randomized across four arms; relevant actual completer denominators unverified.

**Funding:** Abstract access does not establish detailed funding, products, registration or independence.

**Endpoint:** Six-month WAIS-RC, not the selected time point.

**Result:** A human sole-folic-acid arm exists. Combination Full Scale IQ d=0.169 is not a sole-folic-acid effect.

**Weight:** Presence of a relevant intervention arm is distinguished from access to its exact contrast.

### S05 · Li 2024, four FA/DHA arms

**Design:** Abstract reports randomized double-blind placebo control, including sole folic acid 800 micrograms/day.

**Denominators:** 280 total, 70 allocated per group; analysis/completer denominators unverified.

**Funding:** Full funding/product provision and participant independence from related work are unverified; overlapping investigators are identifiable.

**Endpoint:** Twelve-month WAIS-RC Full Scale IQ; different dose, actual comparator and model.

**Result:** Abstract reports sole-FA beta=1.992, 95% CI 1.304–2.679, P<0.001. Modeling, score transformation and missingness are not verified from full text.

**Weight:** Positive adjacent evidence is retained, but not pooled as the 400-microgram/conventional-care effect or promoted to R2.

### S06/S07 · Bai 2021 and its 2023 retraction notice

**Design:** The 2021 paper was formally retracted on 2023-04-25 for ethical-approval and trial-registration issues.

**Denominators:** Retracted participants are not added to valid direct-evidence denominators.

**Funding:** The stated reason is not rewritten as manufacturer funding or proven fabrication.

**Endpoint:** FA/DHA cognition and biomarker work, separate from the sole-addition primary comparison.

**Result:** Excluded from efficacy support. Follow-up/resubmission and participant links to other reports remain unverified.

**Weight:** Retraction and family-overlap control only; no positive efficacy weight.

### Existing 486 and ten other folate candidates

**Design:** Complete candidate records and the 3,159-entry index were reused; combinations, healthy populations, other diagnoses and endpoints remain separate.

**Denominators:** Review totals and copies of the same trial are not new independent participants.

**Funding:** Prior funding classifications and grades are not inherited for this sole-addition claim.

**Endpoint:** Dementia prevention, atrophy, homocysteine, stroke, hemoglobin, MDD, sperm and SBP remain separate from Full Scale IQ.

**Result:** No exact duplicate. Existing 486 F/12 remains historical within its original boundary only.

**Weight:** Reuse and duplicate exclusion, not a new clinical effect estimate.

### S08/S10 · safety context

**Design:** A different 5-mg product SmPC was read; the supplied NIH ODS link is preserved, with current web access unsuccessful.

**Denominators:** General 5-mg product information is not a 400-microgram trial adverse-event denominator.

**Funding:** Official product information is separate from independent efficacy trials.

**Endpoint:** B12-deficiency masking, interactions and adverse events, separate from cognition efficacy.

**Result:** Safety label Caution. Trial arm-specific AE/SAE/discontinuation counts and long-term safety remain unverified.

**Weight:** Unreported does not mean safe; no personal dosing or prescription-change instruction.

## Seven-axis adoption notes

**claim_type:** B: A clinical efficacy question about adding folic acid for cognitive performance in diagnosed MCI. Related human evidence and a direct selected family exist, so no_human_study=false.

**endpoint:** P: A patient-centered functional performance endpoint. The supplied scoring text includes observer-assessed function, whereas the old calculator label says patient-reported more narrowly. WAIS-RC is not self-report and is not dementia incidence or brain atrophy.

**replication:** R1: One registered family for the selected 400-microgram/conventional-care/twelve-month comparison. The old single-confirmatory-trial label does not certify prospective confirmatory status or high quality. Six-, twelve- and twenty-four-month reports are linked; different doses/comparators, overlapping investigators and unverified independence do not establish R2.

**independence:** I2: Public NSFC grant 81130053 and the no-financial-competing-interests declaration were read in decisive source S01. This classifies disclosed funding; it does not certify every product contract, independent replication or external review.

**effect:** E~: The paper-reported d=0.153 is classified against the supplied Case 28 statistical convention of 0.2 only. The legacy below-MCID wording is not adopted literally. No between-group MCID is invented and neither meaningful clinical benefit nor its absence is established. Independent reproduction of d is unverified; Table 5 arithmetic concerns and Table 3’s different estimand are disclosed. A reported magnitude is not relabeled as wholly unreported EX.

**bias:** B2: The decisive randomized sample is 168, below the supplied 200-person small-study criterion, and the no-placebo design leaves investigators aware of allocation with conflicting blinding descriptions. These two actual risks and numerical, registration and missing-data limitations are disclosed without declaring every related study defective.

**precision:** CX: The reported CI is preserved, but its relationship to the coefficient, SE, t and raw-IQ unit is not validated. No claim is made that a valid same-estimand CI excludes or permits clinical benefit. C1, zero effect and equivalence are not adopted.

## Primary sources and access scope

**[S01] Ma et al. Folic acid supplementation improves cognitive function by reducing the levels of peripheral inflammatory cytokines in elderly Chinese subjects with MCI (2016)** — https://www.nature.com/articles/srep37486

DOI: 10.1038/srep37486; PMID: 27876835; full_html; Abstract; Results Tables 1, 3, 4, 5; Methods; Acknowledgements; Competing interests.

**[S02] Ma et al. Effects of 6-Month Folic Acid Supplementation on Cognitive Function and Blood Biomarkers in Mild Cognitive Impairment (2016; online 2015)** — https://pubmed.ncbi.nlm.nih.gov/26508298/

DOI: 10.1093/gerona/glv183; PMID: 26508298; primary_abstract; Abstract; trial number reported in linked primary publication.

**[S03] Ma et al. Effects of folic acid supplementation on cognitive function and Aβ-related biomarkers in mild cognitive impairment: a randomized controlled trial (2019; online 2017)** — https://pubmed.ncbi.nlm.nih.gov/29255930/

DOI: 10.1007/s00394-017-1598-5; PMID: 29255930; primary_abstract; Abstract; trial registration and grant support.

**[S04] Ma et al. Effects of Folic Acid and Vitamin B12, Alone and in Combination on Cognitive Function and Inflammatory Factors in the Elderly with Mild Cognitive Impairment: A Single-blind Experimental Design (2019)** — https://pubmed.ncbi.nlm.nih.gov/31345146/

DOI: 10.2174/1567205016666190725144629; PMID: 31345146; primary_abstract; Abstract.

**[S05] Li et al. Cognitive Benefits of Folic Acid, Docosahexaenoic Acid, and a Combination of Both Nutrients in Mild Cognitive Impairment: Possible Alterations through Mitochondrial Function and DNA Damage (2024)** — https://pubmed.ncbi.nlm.nih.gov/38952108/

DOI: 10.1159/000540021; PMID: 38952108; primary_abstract; Abstract Methods and Results; publisher abstract landing page.

**[S06] Bai et al. RETRACTED: Effects of Folic Acid Combined with DHA Supplementation on Cognitive Function and Amyloid-β-Related Biomarkers (2021)** — https://pubmed.ncbi.nlm.nih.gov/33749643/

DOI: 10.3233/JAD-200997; PMID: 33749643; primary_index_and_publisher_retraction_label; Publisher retracted title; S07.

**[S07] Retraction notice for DOI 10.3233/JAD-200997 (2023)** — https://journals.sagepub.com/doi/full/10.3233/JAD-239002

DOI: 10.3233/JAD-239002; PMID: 37125556; full_html; Notice published 2023-04-25, issue 93(1):393.

**[S08] Folic Acid Tablets 5mg, Flamingo Pharma (UK) Ltd, Summary of Product Characteristics** — https://www.medicines.org.uk/emc/product/14604/smpc

DOI: null; PMID: null; full_official_product_information; Updated 2026-06-05; sections 4.3, 4.4, 4.5, 4.8.

**[S09] ChiCTR-TRC-13003227 registry access attempt** — https://www.chictr.org.cn/showproj.html?proj=6332

DOI: null; PMID: null; landing_response_then_content_error; Legacy URL in S01 redirected; detail retrieval failed.

**[S10] NIH ODS Folate fact sheet: provided safety-source reuse with failed live reopening** — https://ods.od.nih.gov/factsheets/Folate-HealthProfessional/

DOI: null; PMID: null; provided_source_records_only_live_open_failed; The preserved source registers for IDs 3107–3110; live original and print attempts failed.

**[S11] Supplied original folate candidates and selected prior source files** — provided-corpus:input-archive

DOI: null; PMID: null; provided_full_originals; Eleven candidate records, 52 selected originals and prior 79–83 records; see reuse_audit.json for exact unchanged paths and SHA identities.

Written and self-reviewed: 2026-09-17T22:02:30+09:00.

Why this is classified as C (50)

C is the actual grade-function result; 50 is the separate fixed anchor for one I2 strength. Neither is a success probability, official GRADE, manuscript-quality score or external certification.

Counterpoint. Registry-primary status, reproduction of d, a reliable raw-score effect/CI, MCID, formal subtype, total intake, renal function, actual concomitants/adherence/AEs, product contracts and participant independence of the 2024 report remain unverified. Numerical, blinding, missing-data and diagnostic conflicts are disclosed.

Rejudgment record. C/50 reflects one direct registered family, blinding, small-sample, reporting and registry-access limitations. Positive reporting is not rewritten as no effect. — C is the actual grade-function result; 50 is the separate fixed anchor for one I2 strength. Neither is a success probability, official GRADE, manuscript-quality score or external certification.

Review performed and remaining limitations

Original registry detail, complete analysis code, individual data, reproduction of d, a valid raw-score CI, MCID, total intake, renal function, subtype, product contracts and arm-specific adverse events remain unverified. PDF visual verification failed at tool access.

Evidence Table

Receipt — 11 References

Evidence access cutoff: 2026-09-17. 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.