Does adding folic acid 0.8 mg/day for one year lower plasma hs-CRP?
research showsIn Dutch adults aged 50–70 with mildly elevated homocysteine, oral folic acid 0.8 mg/day for one year did not demonstrate lower plasma hs-CRP than matched placebo (P=.88). Participants were not selected for elevated hs-CRP. The current D/28 judgment describes failure to demonstrate improvement in this narrow contrast, not an effect of exactly zero or equivalence for every use of folic acid.
ads claimNo specific advertising copy was collected for this task.
Four separate assessment dimensions
| Effect direction and size | No plasma hs-CRP improvement was demonstrated in the selected 0.8-mg/day, one-year placebo contrast (P=.88). Original mean effect, CI and MCID are null; non-significance is not zero effect or equivalence. |
|---|---|
| Evidence certainty | Current D/28 reflects one source-verified direct family and unverified funding, registration, household correlation and effect magnitude. It does not assert absence of all human research. |
| Applicability | Limited to Dutch homocysteine-screened adults aged 50–70, oral folic-acid capsules 0.8 mg/day, placebo and one-year plasma hs-CRP. Elevated hs-CRP was not a selection criterion. |
| Safety | Caution. Selected-trial AE denominators are unverified; official B12/drug cautions and events in another high-dose trial remain separate. No personal dosing or prescription-change/cessation instructions. |
D is the original grade-function output; 28 is the separate fixed anchor for zero strengths. Neither is a success probability, official GRADE score, document quality or external certification.
Useful facts when choosing a product
- S01 used oral folic-acid capsules 0.8 mg/day manufactured by Swiss Caps Benelux and compared with matched placebo.
- Exact salt, crystal form, raw-material origin, purity, batch, excipients and release profile are unverified.
- This specially manufactured trial capsule does not establish a current product’s anti-inflammatory authorization or a personal dosing recommendation.
Chamgap Semantic Classification Code
Permanent code issued
S.folic-acid-800mcg-supplement-capsule.oral.dutch-age50to70-hcy13plus.one-year-plasma-hscrp-log.matched-placebo-capsuleIngredients > Folic acid, the sole randomized added active ingredient > Oral > Dutch men and postmenopausal women aged 50–70 with screening homocysteine ≥13 micromoles/L. Not selected for elevated hs-CRP; some diabetes/vascular disease. Deficiency/sufficiency subgroups and individual eGFR unverified. > One-year plasma hs-CRP by Dako high-sensitivity ELISA; original distribution in mg/L and a two-sided t test of natural-log endpoint means. Registry-primary status unverified. > Matched placebo capsule. The sole added active ingredient is not necessarily treatment without any background medication; full concomitant-drug balance unverified.
Original D/28, sole added oral folic acid 800 micrograms, one-year plasma hs-CRP,17 uncertainties,both full languages and recorded execution preserved without regrading. The code identifies the intervention and claim; it never contains the evidence grade, score, or safety result.
Exact Claim Classification
These independent facets prevent evidence from different forms, routes, populations, effects, and comparators from being mixed.
| Intervention class | S · Supplement or nutraceutical |
|---|---|
| Canonical ingredient or intervention | Folic acid, the sole randomized added active ingredient |
| Source or part used | Reported as folic acid. Plant part not applicable; manufacturing origin, salt and crystal form unverified. Dietary folate, 5-MTHF and folinic acid excluded. |
| Formulation or processing | Oral 0.8-mg capsule manufactured by Swiss Caps Benelux, not a tablet. Placebo matched in appearance, apparent content and taste; excipients, purity, batch and release profile unverified. |
| Route | Oral |
| Dose | Additional 0.8 mg/day (800 micrograms/day); actual total dietary, fortified and supplemental exposure and DFE unverified. |
| Duration | One-year intervention; assessment at one year ± six weeks, distinct from other 2–52-week and three-year reports. |
| Population | Dutch men and postmenopausal women aged 50–70 with screening homocysteine ≥13 micromoles/L. Not selected for elevated hs-CRP; some diabetes/vascular disease. Deficiency/sufficiency subgroups and individual eGFR unverified. |
| Effect or condition | Additional folic acid for lowering the circulating inflammatory marker hs-CRP |
| Primary endpoint | One-year plasma hs-CRP by Dako high-sensitivity ELISA; original distribution in mg/L and a two-sided t test of natural-log endpoint means. Registry-primary status unverified. |
| Comparator | Matched placebo capsule. The sole added active ingredient is not necessarily treatment without any background medication; full concomitant-drug balance unverified. |
| Duplicate-detection key | folic-acid|supplement-capsule-oral|800mcg-day|Netherlands-age50-70-Hcy13plus|plasma-hsCRP-log-endpoint|one-year|matched-placebo |
What the research actually shows
# Does adding folic acid 0.8 mg/day for one year lower plasma hs-CRP?
TASK-1045 / R01-085 · Input snapshot: 2026-09-17T22:40:55+09:00
## The answer in brief
In Dutch adults aged 50–70 with mildly elevated homocysteine, oral folic acid 0.8 mg/day for one year did not demonstrate lower plasma hs-CRP than matched placebo (P=.88). Participants were not selected for elevated hs-CRP. The current D/28 judgment describes failure to demonstrate improvement in this narrow contrast, not an effect of exactly zero or equivalence for every use of folic acid.
[S01](https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/486617)
## The proposed question and the actual primary comparison
This page has one primary endpoint: **plasma hs-CRP at one year**. The original distribution is in mg/L; the between-arm test is a two-sided t test of natural-log-transformed endpoint means. Proposed elevated-hs-CRP adults, tablets and candidate comparators were not promoted into facts. The verified study used men/postmenopausal women aged 50–70, homocysteine screening, oral capsules and matched placebo.
This contrast was selected editorially because the original assay, denominators, comparator and one-year result could be traced. It was not a prospectively registered review selection or a claim to identify the globally latest/largest study. Whether CRP was a registered primary endpoint remains unverified.
[S01](https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/486617) [S09](https://www.isrctn.com/ISRCTN33564325)
## Population and baseline inflammation boundaries
The community sample was selected for screening homocysteine ≥13 micromoles/L. The last 530 participants from an 819-person parent trial entered this inflammatory-marker analysis. It was not a uniform population with one diagnosed inflammatory disease; some participants had diabetes or vascular disease. Baseline CRP medians were 1.5 mg/L with folic acid and 1.1 with placebo. It is incorrect to describe everyone as having elevated CRP, being healthy or having adequate folate intake.
Exclusions included renal/thyroid disease, B12 <271 pg/mL (200 pmol/L), specified B-vitamin supplements or medications affecting folate metabolism/atherosclerosis, and <80% run-in adherence. Excluding low B12 does not guarantee subsequent B12-related safety.
[S01](https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/486617)
## Nutrition, renal function and actual total exposure
Baseline serum-folate medians (IQRs) were 4.9 (4.0–6.2) versus 4.9 (4.0–6.6) ng/mL. Dietary folate was 186 (156–230) versus 202 (161–250) micrograms/day, from the baseline FFQ covering the preceding three months. B12 was 391.6 (336.0–497.3) versus 390.2 (333.3–491.9) pg/mL; creatinine was mean±SD 1.0±0.1 versus 1.1±0.1 mg/dL.
The study was not selected to treat diagnosed folate deficiency. Individual deficiency/sufficiency classifications, eGFR and renal subgroups remain unverified. Adding 800 micrograms to a baseline dietary median would not establish actual total exposure or DFE. Actual follow-up intake including diet, fortification and individual adherence is null.
[S01](https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/486617)
## Molecular form, formulation, dose and comparator
The intervention was an oral folic-acid capsule providing 0.8 mg/day (800 micrograms/day), manufactured by Swiss Caps Benelux and matched to placebo in yellow appearance, apparent contents and taste. It was not a tablet, 5-MTHF, folinic acid, food/fortification or a B6/B12 combination. Exact salt, crystal form, manufacturing origin, batch, purity, excipients and release properties were not verified.
Folic acid was the sole randomized additional active ingredient, which does not imply treatment without any background medication. Complete concomitant-drug distributions and changes remain unverified. The specially manufactured capsule does not establish a currently marketed product or authorized anti-inflammatory indication.
[S01](https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/486617) [S07](https://ods.od.nih.gov/factsheets/Folate-HealthProfessional/)
## Specimen, assay and measurement scope
Methods describe fasting K3EDTA plasma, immediate centrifugation and storage at −80°C. hs-CRP was measured by Dako high-sensitivity ELISA; intra-/inter-assay coefficients of variation were 6.0%/9.7%. The CRP reader, reagent catalogue/lot, detection/quantification limits and exact sampling clock time were unverified. The 400-pg/mL detection limit for sICAM-1 and instruments for creatinine/vitamins were not transferred to CRP.
The abstract methods say serum, whereas detailed specimen methods and results say plasma. This terminology conflict is retained, with plasma adopted from the detailed methods. Routine CRP versus a high-sensitivity assay, serum versus plasma, and original versus logarithmic concentrations are not merged.
[S01](https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/486617)
## Original denominators, attrition and adherence
The allocated analysis population was 264 with folic acid and 266 with placebo, totaling 530. Five/four did not return at one year, leaving an arithmetically derived observed follow-up sample of 259/262, totaling 521. The reported ITT analysis imputed baseline values as endpoints for nine participants. Parent-trial 819, inflammatory-analysis 530 and observed-visit 521 are different denominators.
All except two reported >90% capsule use from returns/self-report. The lowest reported adherence in a three-month period was 52%. Run-in selection and self-report impose limitations. Homocysteine reduction supports exposure but is not evidence of CRP improvement.
[S01](https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/486617)
## Primary endpoint values and test
| Item | Folic acid | Placebo | Meaning | |---|---:|---:|---| | Baseline hs-CRP, mg/L | 1.5 (0.7–3.1) | 1.1 (0.6–2.4) | Median (IQR) | | One-year hs-CRP, mg/L | 1.4 (0.9–3.1) | 1.2 (0.6–3.1) | Median (IQR) | | ITT analysis n | 264 | 266 | Includes baseline-value imputation | | One-year between-arm test | P=.88 | — | Two-sided t test of natural-log endpoint means |
The simple difference 1.4−1.2=0.2 mg/L is a difference between group medians, not the paper’s estimated mean difference or adjusted effect. Subtracting each group’s baseline and endpoint medians is not a mean of individual changes. P=.88 is not labelled a median rank test or a within-arm test. The paper says baseline adjustment left conclusions unchanged, but an adjusted coefficient, SE and CI were not obtained in the accessible material.
[S01](https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/486617)
## Recalculation and clinical meaning
Arithmetic checks give 264+266=530, 530−9=521 and 1.698113% missing follow-up. Medians/IQRs were not arbitrarily converted to normally distributed means/SDs. Assuming an independent equal-variance log-scale t test with P=.88 and df=528 yields |t|≈0.151042 and |d_log|≈0.013122. This is a conditional approximation inverted from rounded P, not an effect calculated from the original table; it provides no sign, raw mg/L difference, adjusted effect, CI or MCID. Unverified household dependence and log distributions preclude adoption as the primary effect.
A verified raw mean difference/geometric-mean ratio, CI and MCID remain null with reasons. Non-significance is not equivalence or an exact zero. CRP changes alone do not establish clinical benefit for symptoms, infection, cardiovascular events, cancer or immune function.
[S01](https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/486617)
## Randomization, blinding and household structure
Computer-generated permuted blocks of four/six, an externally supplied random list and unique allocation codes are described. Allocation/distribution/blood-draw staff and analysts were code-blinded; analysts received fake participant numbers. People sharing a household received the same intervention. Household counts, ICC and household-correlation adjustment are unverified, so 530 fully independent observations cannot be guaranteed.
The reported blinding questionnaire in a 260-person three-year subgroup is not a blinding test of all 530 participants at one year. This selected analysis is parallel, not crossover. Unverified registered/analysis priority and multiple-marker testing are disclosed without asserting confirmed post-hoc selection or failed randomization.
[S01](https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/486617) [S09](https://www.isrctn.com/ISRCTN33564325)
## Related-programme reports and overlap
Klerk’s 2005 abstract describes 276 adults, 0.8 mg/day, one year and placebo, without a clear CRP change. Investigators/programme are related to Durga, but individual overlap and separate funding were not verified. The reports are neither asserted to involve identical people nor counted as independent replication. Conservatively, no additional independent trial is added. The repository’s mM screening-homocysteine unit issue is not silently corrected.
Other cognitive/vascular endpoints from the parent programme, follow-up reports, article copies and a review plus its included trials are not separate independent replications.
[S01](https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/486617) [S02](https://repository.tno.nl/SingleDoc?docId=58290)
## The 2021 meta-analysis and its original-source discrepancy
The 2021 review reports pooled CRP −0.59 mg/L, approximately 95% CI −0.85 to −0.33 (an upper bound of −0.32 also appears in the text), with I²=91.3%. It combines different diseases, doses and durations. Its Durga row shows −0.20 mg/L, CI −0.26 to −0.14, implying a significant decrease, whereas the original provides medians/IQRs and a log-test P=.88. That row’s estimand and variance could not be reproduced from the original. The Klerk row also differs from the abstract’s non-significant interpretation and remains unresolved.
This is not an allegation of proven fabrication. The original and review are not added as independent evidence. Without extraction reconciliation, the pooled number is not adopted as the selected contrast’s effect. High I² alone does not justify the supplied R0 code.
[S01](https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/486617) [S02](https://repository.tno.nl/SingleDoc?docId=58290) [S03](https://pdfs.semanticscholar.org/8618/6d56c39be4f1be2648a8e834d41821b7514f.pdf)
## Positive reports in another disease population
El-khodary 2022 compared folic-acid tablets 5 mg/day with placebo for twelve weeks in type 2 diabetes patients maintained on metformin 1500 mg/day. The analysis used 100 people, fifty per arm; the sequence linking the initial 105 and five non-adherence exclusions/ITT could not be fully reconciled in the accessible material. Glycemic outcomes were primary; registered hs-CRP priority was unverified.
Original methods specify serum hs-CRP by Dade Behring BNII nephelometry, distinct from the review’s ELISA label. The accessible narrative’s folic-arm 464.69±65.21→438.05±39.04 and P=.008 are within-arm figures without verified units or the original placebo row. That P is not a between-arm effect, and the figures are not assigned mg/L. The authors’ positive interpretation is preserved, but the verified original between-arm effect/CI is null. This higher-dose/diabetes/twelve-week comparison is not pooled with community 0.8-mg/one-year results.
[S04](https://www.nature.com/articles/s41387-022-00210-6) [S05](https://d-nb.info/1334955549/34)
## Interpretation of the 2024 diabetes review
The 2024 diabetes review reports CRP SMD −0.68, 95% CI −1.34 to −0.01, P=.05. This is not mg/L. Sensitivity analysis excluding El-khodary gives SMD −0.63, CI −1.56 to 0.30, P=.16, remaining uncertain. These samples are not counted as new independent original trials. The PDF text was read, but two attempts at visual table verification failed with tool errors.
Short diabetes crossover trials, other doses and other inflammatory markers in that review are distinct from the selected one-year plasma hs-CRP endpoint. A multi-arm study can contain a folic-acid-only arm; it is not discarded mechanically, but actual eligible comparisons and access levels remain separate.
[S05](https://d-nb.info/1334955549/34)
## Expression of Concern and the PCOS shared control
Bahmani 2014 randomized 69 women with PCOS to 1 mg/day, 5 mg/day or placebo, twenty-three each, for eight weeks. The abstract’s hs-CRP changes in 5-mg/1-mg/placebo order are −212.2/−262.4/+729.8 micrograms/L. Simple unit conversion gives −0.2122/−0.2624/+0.7298 mg/L, not verified adjusted between-arm effects or CIs. Two doses sharing one placebo group are not two independent trials. The abstract calls the intervention folate; its precise molecule/salt was not verified from full text.
The official Expression of Concern dated 2023-02-27 (DOI 10.1111/cen.14893) says that doubts about feasibility and integrity persisted after investigation because clinical records were not verified. This is distinct from a retraction or proven fabrication. The report is retained as an evidence-map/integrity warning, not definitive positive efficacy evidence.
[S06](https://onlinelibrary.wiley.com/doi/10.1111/cen.12451) [S08](https://onlinelibrary.wiley.com/doi/10.1111/cen.14893)
## Trial families and replication handling
Title 2006 (nineteen people) and Moens 2007 (twenty) are mapped as crossover designs in the 2021 review; their periods are not added as independent parallel groups. Shared-placebo splitting in Bahmani 2014, unverified Durga/Klerk participant linkage and parent-trial follow-up are distinguished in trial_families.json. Mangoni, Spoelstra-de-Man, Solini, Asemi, Talari and Bahmani 2018 are review-mapped studies at other doses/in other diseases, not all verified full-text extractions.
The 2025 folic-acid/B12/rosuvastatin combination was excluded for additional B12. The 2026 observational folic-dose/cardiovascular-event study in methotrexate-treated RA was excluded by design/endpoint; this is methotrexate, not metformin. A 2026 umbrella review was checked but not counted as a new direct CRP trial. A bounded search is not proof that human research does not exist.
[S02](https://repository.tno.nl/SingleDoc?docId=58290) [S03](https://pdfs.semanticscholar.org/8618/6d56c39be4f1be2648a8e834d41821b7514f.pdf) [S10](https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2025.1604862/full) [S11](https://journals.sagepub.com/doi/full/10.1177/1759720X261423837) [S12](https://jogh.org/2026/jogh-16-04160/)
## Related human evidence, direct eligibility and access
Related human evidence exists. Direct original-source access for the selected boundary was obtained for one Durga family. Klerk provides a similar-contrast abstract but independence/overlap remains unverified. Diabetes, PCOS and other-dose studies are adjacent human evidence, not independent replications of this exact contrast. Registry holding pages, table-fetch errors and abstract-only articles are labelled separately. Searches and access to every database or full paper are not claimed.
[S01](https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/486617) [S02](https://repository.tno.nl/SingleDoc?docId=58290) [S04](https://www.nature.com/articles/s41387-022-00210-6) [S06](https://onlinelibrary.wiley.com/doi/10.1111/cen.12451) [S09](https://www.isrctn.com/ISRCTN33564325)
## Seven axes and D/28
The seven adopted axes are **B / S / R1 / I1 / E0 / B1 / CX**. The E0 floor gives D. None of the supplied anchor strengths H/R2/I2/E+/C1/B0/large-hard-endpoint-trial is verified, so the D row with zero strengths gives **28 points**. The grade function and numerical anchor are separate. Unknown funding was not inherited as I2, and the previous item’s C/50 or other folic-acid axes were not copied.
The supplied case 29 (unknown funding), case 31 (comparability/independence), case 44 (B0 verification gate), E0 floor and fixed score anchor were applied. Legacy R1/I1/E0 labels must be read with the actual meanings below.
## Claim type
B: An efficacy claim about randomized additional folic acid lowering CRP, not a chemical fact or safety-only question.
## Endpoint axis
S: Plasma hs-CRP concentration is a surrogate, not a hard clinical endpoint establishing anti-inflammatory treatment, fewer infections, cancer prevention or immune enhancement.
## Replication axis
R1: One source-verified trial family for the selected contrast. The legacy label single confirmatory trial does not mean a prospectively registered primary endpoint was verified. Klerk overlap/funding and comparability of other disease/dose contrasts are unverified; R2, RX and R0 are not assigned (case 31).
## Independence axis
I1: The prescribed case-29 value for unverified funding/product contracts. The legacy label mixed does not assert verified public/industry mixed funding. Swiss Caps manufacture or university affiliation does not justify I2.
## Effect axis
E0: Failure to demonstrate between-group hs-CRP improvement in this 0.8-mg/placebo/one-year contrast (P=.88). The legacy label ineffective is not an effect of exactly zero, equivalence or absence of every folic-acid effect. Magnitude, CI and MCID remain unverified; benefit exclusion is not claimed. The supplied E0 rule is applied to a verified non-significant contrast, rather than treating it as a positive effect with unknown magnitude under EX.
## Bias axis
B1: One reporting/selection domain reflecting inability to verify the registered endpoint/analysis plan, failing the case-44 B0 gate. Multiple markers and household-correlation limitations are disclosed without inventing confirmed endpoint switching or allocation failure, or double-counting funding and precision.
## Precision axis
CX: No verified raw-scale or log-scale effect CI supports a C1 benefit-exclusion or C0 benefit-compatible CI classification. P=.88 alone does not establish equivalence or a precise zero.
## Safety: Caution
Arm-specific AE, SAE and toxicity-withdrawal counts/exposure denominators for the selected 0.8-mg/one-year trial remain unverified. The nine missed visits were not all classified as adverse-event withdrawals, and non-reporting was not converted into zero events or confirmed safety. General official information describes possible masking of hematologic B12-deficiency signs and delayed recognition of neurological injury; this does not establish that the selected trial observed that harm.
The 5-mg/twelve-week diabetes trial reports nausea/loss of appetite 14% versus 8%, bloating/gas/stomach pain 12% versus 2%, unpleasant taste 10% versus 2%, and confusion 6% versus 0%. These are not adverse-event rates for the selected 0.8-mg trial. Non-significant differences do not establish identical safety.
Methotrexate in cancer versus low-dose RA and interactions with antiepileptics involve different contexts. No change or discontinuation of prescribed folate or other medication is directed. Findings are not generalized to renal disease/dialysis, children, pregnancy/lactation or prolonged high-dose use. Research doses are not personal dosing or replacement-of-standard-treatment recommendations.
[S01](https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/486617) [S04](https://www.nature.com/articles/s41387-022-00210-6) [S07](https://ods.od.nih.gov/factsheets/Folate-HealthProfessional/)
## Pre-submission corrections and remaining unknowns
Original-source comparison fixed proposed elevated-hs-CRP selection to actual homocysteine selection, tablets to capsules, and an unqualified serum label to detailed-method plasma with the abstract conflict retained. The meta-analysis’s significant Durga row was not adopted as the original effect. The PCOS Expression of Concern was added, and the diabetes within-arm P, units and assay were separated. These are pre-first-publication audit records, not post-publication corrections; initial corrections=[].
Registry detail, funding/product contracts, individual nutrition/total intake/renal status, household correlation, verified effect/CI/MCID/AE denominators, Klerk overlap, review extraction reconciliation and some original tables remain unverified. Each is completed as null with bilingual reasons and revision conditions; clinical_todo=[]. Clinical re-investigation of missing numbers or independence is not handed to the technical recipient.
[S01](https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/486617) [S03](https://pdfs.semanticscholar.org/8618/6d56c39be4f1be2648a8e834d41821b7514f.pdf) [S04](https://www.nature.com/articles/s41387-022-00210-6) [S08](https://onlinelibrary.wiley.com/doi/10.1111/cen.14893)
## Completion, separate quality and revision conditions
Content is completed_with_uncertainty; technical identifiers are needs_id_assignment. New ID, slug, URL, semantic code and first-publication date are null. Self-assessed document quality A describes completed traceability, uncertainty disclosure, bilingual content and format; it is separate from efficacy D/28, safety Caution and external independent review. Same-model self-review, translation and technical restoration are not journal certification or independent clinical replication.
Accessible linked registry/protocols, original analyses/tables, funding, corrections/retractions, new independent trials within the same boundary or a validated clinically important threshold would trigger revision while retaining any assigned publication ID. The current value is not on clinical hold. Only original preservation, identifier/classification connection, display/build/deployment are technical next steps; this run performs no server access/deployment and does not start item 86.
## Structural and original-source links
`numeric_evidence.json` preserves source numbers, `numeric_check_receipt.json` actual arithmetic, `trial_families.json` dependency mapping, `sources.json` access/identifiers, and four files in `grading/` the original-calculator and separate-anchor receipts. This full text exactly equals this language’s body_markdown and what_research. The separate research_report.md records bilingual research decisions and is a different file.
Why this is classified as D (28)
D is the original grade-function output; 28 is the separate fixed anchor for zero strengths. Neither is a success probability, official GRADE score, document quality or external certification.
Counterpoint. Registry/funding, original effect/CI, MCID, total intake, renal status, household correlation, AEs, Klerk overlap, meta-extraction reconciliation and some original tables remain unverified. Access failures are disclosed.
| Claim type | B | B: An efficacy claim about randomized additional folic acid lowering CRP, not a chemical fact or safety-only question. |
| Endpoint | S | S: Plasma hs-CRP concentration is a surrogate, not a hard clinical endpoint establishing anti-inflammatory treatment, fewer infections, cancer prevention or immune enhancement. |
| Replication | R1 | R1: One source-verified trial family for the selected contrast. The legacy label single confirmatory trial does not mean a prospectively registered primary endpoint was verified. Klerk overlap/funding and comparability of other disease/dose contrasts are unverified; R2, RX and R0 are not assigned (case 31). |
| Independence | I1 | I1: The prescribed case-29 value for unverified funding/product contracts. The legacy label mixed does not assert verified public/industry mixed funding. Swiss Caps manufacture or university affiliation does not justify I2. |
| Effect size | E0 | E0: Failure to demonstrate between-group hs-CRP improvement in this 0.8-mg/placebo/one-year contrast (P=.88). The legacy label ineffective is not an effect of exactly zero, equivalence or absence of every folic-acid effect. Magnitude, CI and MCID remain unverified; benefit exclusion is not claimed. The supplied E0 rule is applied to a verified non-significant contrast, rather than treating it as a positive effect with unknown magnitude under EX. |
| Precision | CX | CX: No verified raw-scale or log-scale effect CI supports a C1 benefit-exclusion or C0 benefit-compatible CI classification. P=.88 alone does not establish equivalence or a precise zero. |
| Risk of bias | B1 | B1: One reporting/selection domain reflecting inability to verify the registered endpoint/analysis plan, failing the case-44 B0 gate. Multiple markers and household-correlation limitations are disclosed without inventing confirmed endpoint switching or allocation failure, or double-counting funding and precision. |
Stored derived and displayed grades match; this is not a current recalculation or validity check (D).
Review performed and remaining limitations
Registry/funding, original effect/CI, MCID, total intake, renal status, household correlation, AEs, Klerk overlap, meta-extraction reconciliation and some original tables remain unverified. Access failures are disclosed.
Evidence Table
| Study | Design | Sample | Funding | Endpoint | Result | Weight |
|---|---|---|---|---|---|---|
| Durga 2005 · FAM-FACIT-CRP | Randomized placebo parallel contrast with same-household intervention linkage. Original HTML/tables and table image reviewed. | ITT 264/266=530; observed one-year visits 259/262=521; baseline imputed for nine. | Funding/product contracts unverified. Swiss Caps manufacture is not verified independent public funding. | One-year plasma hs-CRP; mg/L medians/IQRs distinct from a log-mean test. | Endpoint 1.4 (0.9–3.1) versus 1.2 (0.6–3.1) mg/L; between-arm P=.88. Original mean effect, CI and MCID null. | One selected direct original trial family. Non-significance is not an exact zero or equivalence. |
| Klerk 2005 · related programme | 0.8 mg/day for one year versus placebo; original-author repository abstract only. | 276 reported; overlap/disjointness with other reports unverified. | Abstract access did not verify separate funding, product support or independence. | CRP; exact assay, original units/figures and registered priority unverified. | Abstract reports no clear change. Repository screening-homocysteine mM unit issue retained. | Related human evidence exists. Not added as separate independent R2/RX replication. |
| Asbaghi 2021 evidence map | Meta-analysis of existing RCTs; PDF CRP forest and characteristics table visually inspected. | Reported CRP eleven reports/twelve effects/1279 people not re-certified as unique independent participants. | Review independence is not transferred to original-trial funding. | CRP across diseases, doses and durations; unit/estimand incompatibility possible. | Pooled −0.59 mg/L, approximate CI −0.85 to −0.33, I²91.3%. Durga row −0.20 [−0.26,−0.14] conflicts with original P=.88. | Trial mapping/extraction audit only, not a new selected-contrast estimate or independent replication. |
| El-khodary 2022 · type 2 diabetes | Added folic-acid tablets 5 mg/day versus placebo on metformin 1500 mg/day for twelve weeks. HTML accessed; separate table fetches failed. | Analyzed 50/50=100; exact ITT sequence from initial 105 and five exclusions unverified. | Does not establish funding independence of the selected 0.8-mg trial. | Serum hs-CRP by Dade Behring BNII nephelometry; registered CRP priority unverified. | Authors’ positive interpretation retained. Narrative within-arm P=.008 is not between-arm P; original unit/placebo row/effect/CI null. | Adjacent evidence in another disease/dose/time frame, not pooled into the selected contrast. |
| Mokgalaboni 2024 · diabetes map | Meta-analysis of existing studies; original PDF text only, two visual attempts failed. | Nine studies/426 people reported overall, not the verified unique CRP denominator. | Review evaluation, certification or funding is not inherited as original-trial I2. | CRP SMD is not mg/L; short crossover designs and doses distinguished. | SMD −0.68 [−1.34,−0.01], P=.05; without El-khodary −0.63 [−1.56,0.30], P=.16. | Adjacent uncertainty context; original evidence not double-counted. |
| Bahmani 2014 and 2023 Expression of Concern | Three-arm PCOS trial, eight weeks; original abstract and full official concern notice reviewed. | Twenty-three each for 1 mg/5 mg/placebo, total 69; one shared placebo. | Official concern about unverified clinical records is not converted into invented industry funding or proven fabrication. | Abstract serum hs-CRP changes in micrograms/L; molecule/salt and detailed analysis unverified from full text. | 5-mg/1-mg/placebo changes −212.2/−262.4/+729.8 micrograms/L. Expression of Concern 2023-02-27, not a retraction. | Integrity warning/mapping only; no definitive positive efficacy weight. |
| Official safety and twelve existing-candidate boundaries | Current NIH ODS official text plus twelve supplied original candidate JSONs and selected manuscripts/sources. | No selected-trial adverse-event denominator invented from general safety material. | Official safety documents, technical tests and old grades do not establish new clinical independence. | B12 masking, concomitant-drug context and other folic-acid claims distinct from this CRP question. | No exact duplicate; safety Caution. Related human evidence, exact direct evidence and access recorded separately. | Safety/boundary reuse only; old efficacy, quality and axes not inherited. |
Receipt — 12 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.
Technical integration by: Codex · Evidence date: 2026-09-17 · Corrections: none
Cite this verdict
[Chamgap] Does adding folic acid 0.8 mg/day for one year lower plasma hs-CRP? — Evidence Grade D·28. 12 cited sources checked. Source: https://chamgap.com/en/verdicts/antioxidant-aging/folic-acid-800mcg-one-year-plasma-hscrp-matched-placebo/ · CC BY 4.0CC BY 4.0 — free to use with attribution; do not distort grades, numbers, or verdict meaning.
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