Nutrient chapter

Fulvic acid (heterogeneous humic fraction)

Operational heterogeneous humic fraction, not a single molecular structure or established essential nutrient. Individual preparations and the distinct fungal molecule CAS 479-66-3 are recorded separately.

42 recorded mechanisms · 0 availability situations · 4 preserved sources. Draft and verified records are labeled separately.

Read recorded mechanisms Open recursive mind map

The mechanisms

What the sources say this nutrient does, one relationship at a time. Plain wording comes first; the technical statement follows.

Added homocysteine increased ERK phosphorylation in U937 cells.
Homocysteine → Human ERK1/ERK2 kinases source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Human primary monocytes and U937 cells; Esther 20% stock diluted to 0.5-10 micrograms/mL, 4-hour pretreatment; homocysteine stimulation.
limitations
Cell exposure does not establish oral exposure, homocysteine removal or cardiovascular benefit. Results text reports homocysteine 200 micromolar, while figure captions say 200 micrograms/mL; dose units are unresolved. Inhibitor concentrations also need original-record clarification.
nutrient_topic
Fulvic acid collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Fulvic acid (heterogeneous humic fraction)
plain_language
Homocysteine activated an inflammatory signaling branch.
primary_references
Fulvic acid attenuates homocysteine-induced cyclooxygenase-2 expression in human monocytes. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25888188/ · DOI 10.1186/s12906-015-0583-x
Fulvic acid: mixture identity, mineral chemistry, signaling and cross-nutrient mechanisms (2026-09-19) · lines 20–26
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human primary monocytes and U937 cells; Esther 20% stock diluted to 0.5-10 micrograms/mL, 4-hour pretreatment; homocysteine stimulation. · source_derived_draft · unverified_draft
## fulvic-acid-hcy-erk Homocysteine activated an inflammatory signaling branch. Added homocysteine increased ERK phosphorylation in U937 cells. Model: Human primary monocytes and U937 cells; Esther 20% stock diluted to 0.5-10 micrograms/mL, 4-hour pretreatment; homocysteine stimulation. Limitations: Cell exposure does not establish oral exposure, homocysteine removal or cardiovascular benefit. Results text reports homocysteine 200 micromolar, while figure captions say 200 micrograms/mL; dose units are unresolved. Inhibitor concentrations also need original-record clarification. Evidence access: Primary full text Fulvic acid attenuates homocysteine-induced cyclooxygenase-2 expression in human monocytes. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25888188/ · DOI 10.1186/s12906-015-0583-x
Complete structured claim and evidence
Added homocysteine increased JNK phosphorylation in U937 cells.
Homocysteine → Human JNK1/JNK2 assay pool source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Human primary monocytes and U937 cells; Esther 20% stock diluted to 0.5-10 micrograms/mL, 4-hour pretreatment; homocysteine stimulation.
limitations
Cell exposure does not establish oral exposure, homocysteine removal or cardiovascular benefit. Results text reports homocysteine 200 micromolar, while figure captions say 200 micrograms/mL; dose units are unresolved. Inhibitor concentrations also need original-record clarification.
nutrient_topic
Fulvic acid collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Fulvic acid (heterogeneous humic fraction)
plain_language
A second kinase branch responded to homocysteine.
primary_references
Fulvic acid attenuates homocysteine-induced cyclooxygenase-2 expression in human monocytes. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25888188/ · DOI 10.1186/s12906-015-0583-x
Fulvic acid: mixture identity, mineral chemistry, signaling and cross-nutrient mechanisms (2026-09-19) · lines 28–34
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human primary monocytes and U937 cells; Esther 20% stock diluted to 0.5-10 micrograms/mL, 4-hour pretreatment; homocysteine stimulation. · source_derived_draft · unverified_draft
## fulvic-acid-hcy-jnk A second kinase branch responded to homocysteine. Added homocysteine increased JNK phosphorylation in U937 cells. Model: Human primary monocytes and U937 cells; Esther 20% stock diluted to 0.5-10 micrograms/mL, 4-hour pretreatment; homocysteine stimulation. Limitations: Cell exposure does not establish oral exposure, homocysteine removal or cardiovascular benefit. Results text reports homocysteine 200 micromolar, while figure captions say 200 micrograms/mL; dose units are unresolved. Inhibitor concentrations also need original-record clarification. Evidence access: Primary full text Fulvic acid attenuates homocysteine-induced cyclooxygenase-2 expression in human monocytes. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25888188/ · DOI 10.1186/s12906-015-0583-x
Complete structured claim and evidence
Fulvic pretreatment reduced homocysteine-stimulated ERK phosphorylation.
Esther Material Technology fulvic preparation, 2015 study → Human ERK1/ERK2 kinases source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Human primary monocytes and U937 cells; Esther 20% stock diluted to 0.5-10 micrograms/mL, 4-hour pretreatment; homocysteine stimulation.
limitations
Cell exposure does not establish oral exposure, homocysteine removal or cardiovascular benefit. Results text reports homocysteine 200 micromolar, while figure captions say 200 micrograms/mL; dose units are unresolved. Inhibitor concentrations also need original-record clarification.
nutrient_topic
Fulvic acid collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Fulvic acid (heterogeneous humic fraction)
plain_language
The preparation dampened the ERK response.
primary_references
Fulvic acid attenuates homocysteine-induced cyclooxygenase-2 expression in human monocytes. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25888188/ · DOI 10.1186/s12906-015-0583-x
Fulvic acid: mixture identity, mineral chemistry, signaling and cross-nutrient mechanisms (2026-09-19) · lines 36–42
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human primary monocytes and U937 cells; Esther 20% stock diluted to 0.5-10 micrograms/mL, 4-hour pretreatment; homocysteine stimulation. · source_derived_draft · unverified_draft
## fulvic-acid-fa-erk The preparation dampened the ERK response. Fulvic pretreatment reduced homocysteine-stimulated ERK phosphorylation. Model: Human primary monocytes and U937 cells; Esther 20% stock diluted to 0.5-10 micrograms/mL, 4-hour pretreatment; homocysteine stimulation. Limitations: Cell exposure does not establish oral exposure, homocysteine removal or cardiovascular benefit. Results text reports homocysteine 200 micromolar, while figure captions say 200 micrograms/mL; dose units are unresolved. Inhibitor concentrations also need original-record clarification. Evidence access: Primary full text Fulvic acid attenuates homocysteine-induced cyclooxygenase-2 expression in human monocytes. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25888188/ · DOI 10.1186/s12906-015-0583-x
Complete structured claim and evidence
Fulvic pretreatment reduced homocysteine-stimulated JNK phosphorylation.
Esther Material Technology fulvic preparation, 2015 study → Human JNK1/JNK2 assay pool source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Human primary monocytes and U937 cells; Esther 20% stock diluted to 0.5-10 micrograms/mL, 4-hour pretreatment; homocysteine stimulation.
limitations
Cell exposure does not establish oral exposure, homocysteine removal or cardiovascular benefit. Results text reports homocysteine 200 micromolar, while figure captions say 200 micrograms/mL; dose units are unresolved. Inhibitor concentrations also need original-record clarification.
nutrient_topic
Fulvic acid collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Fulvic acid (heterogeneous humic fraction)
plain_language
The preparation dampened the JNK response.
primary_references
Fulvic acid attenuates homocysteine-induced cyclooxygenase-2 expression in human monocytes. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25888188/ · DOI 10.1186/s12906-015-0583-x
Fulvic acid: mixture identity, mineral chemistry, signaling and cross-nutrient mechanisms (2026-09-19) · lines 44–50
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human primary monocytes and U937 cells; Esther 20% stock diluted to 0.5-10 micrograms/mL, 4-hour pretreatment; homocysteine stimulation. · source_derived_draft · unverified_draft
## fulvic-acid-fa-jnk The preparation dampened the JNK response. Fulvic pretreatment reduced homocysteine-stimulated JNK phosphorylation. Model: Human primary monocytes and U937 cells; Esther 20% stock diluted to 0.5-10 micrograms/mL, 4-hour pretreatment; homocysteine stimulation. Limitations: Cell exposure does not establish oral exposure, homocysteine removal or cardiovascular benefit. Results text reports homocysteine 200 micromolar, while figure captions say 200 micrograms/mL; dose units are unresolved. Inhibitor concentrations also need original-record clarification. Evidence access: Primary full text Fulvic acid attenuates homocysteine-induced cyclooxygenase-2 expression in human monocytes. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25888188/ · DOI 10.1186/s12906-015-0583-x
Complete structured claim and evidence
Fulvic pretreatment reduced p65 binding at the COX-2 promoter in stimulated U937 cells.
Esther Material Technology fulvic preparation, 2015 study → Human NF-kappa-B p65 / RELA source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Human primary monocytes and U937 cells; Esther 20% stock diluted to 0.5-10 micrograms/mL, 4-hour pretreatment; homocysteine stimulation.
limitations
Cell exposure does not establish oral exposure, homocysteine removal or cardiovascular benefit. Results text reports homocysteine 200 micromolar, while figure captions say 200 micrograms/mL; dose units are unresolved. Inhibitor concentrations also need original-record clarification. ChIP is a cultured-cell result; the paper uses in vivo to mean within cells.
nutrient_topic
Fulvic acid collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Fulvic acid (heterogeneous humic fraction)
plain_language
The inflammatory transcription factor occupied the promoter less.
primary_references
Fulvic acid attenuates homocysteine-induced cyclooxygenase-2 expression in human monocytes. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25888188/ · DOI 10.1186/s12906-015-0583-x
Fulvic acid: mixture identity, mineral chemistry, signaling and cross-nutrient mechanisms (2026-09-19) · lines 52–58
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human primary monocytes and U937 cells; Esther 20% stock diluted to 0.5-10 micrograms/mL, 4-hour pretreatment; homocysteine stimulation. · source_derived_draft · unverified_draft
## fulvic-acid-p65-binding The inflammatory transcription factor occupied the promoter less. Fulvic pretreatment reduced p65 binding at the COX-2 promoter in stimulated U937 cells. Model: Human primary monocytes and U937 cells; Esther 20% stock diluted to 0.5-10 micrograms/mL, 4-hour pretreatment; homocysteine stimulation. Limitations: Cell exposure does not establish oral exposure, homocysteine removal or cardiovascular benefit. Results text reports homocysteine 200 micromolar, while figure captions say 200 micrograms/mL; dose units are unresolved. Inhibitor concentrations also need original-record clarification. ChIP is a cultured-cell result; the paper uses in vivo to mean within cells. Evidence access: Primary full text Fulvic acid attenuates homocysteine-induced cyclooxygenase-2 expression in human monocytes. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25888188/ · DOI 10.1186/s12906-015-0583-x
Complete structured claim and evidence
Fulvic pretreatment reduced homocysteine-induced COX-2 mRNA in primary monocytes and U937 cells.
Esther Material Technology fulvic preparation, 2015 study → Cyclooxygenase-2 (PTGS2) source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Human primary monocytes and U937 cells; Esther 20% stock diluted to 0.5-10 micrograms/mL, 4-hour pretreatment; homocysteine stimulation.
limitations
Cell exposure does not establish oral exposure, homocysteine removal or cardiovascular benefit. Results text reports homocysteine 200 micromolar, while figure captions say 200 micrograms/mL; dose units are unresolved. Inhibitor concentrations also need original-record clarification.
nutrient_topic
Fulvic acid collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Fulvic acid (heterogeneous humic fraction)
plain_language
Less inflammatory-enzyme message was produced.
primary_references
Fulvic acid attenuates homocysteine-induced cyclooxygenase-2 expression in human monocytes. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25888188/ · DOI 10.1186/s12906-015-0583-x
Fulvic acid: mixture identity, mineral chemistry, signaling and cross-nutrient mechanisms (2026-09-19) · lines 60–66
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human primary monocytes and U937 cells; Esther 20% stock diluted to 0.5-10 micrograms/mL, 4-hour pretreatment; homocysteine stimulation. · source_derived_draft · unverified_draft
## fulvic-acid-cox-expression Less inflammatory-enzyme message was produced. Fulvic pretreatment reduced homocysteine-induced COX-2 mRNA in primary monocytes and U937 cells. Model: Human primary monocytes and U937 cells; Esther 20% stock diluted to 0.5-10 micrograms/mL, 4-hour pretreatment; homocysteine stimulation. Limitations: Cell exposure does not establish oral exposure, homocysteine removal or cardiovascular benefit. Results text reports homocysteine 200 micromolar, while figure captions say 200 micrograms/mL; dose units are unresolved. Inhibitor concentrations also need original-record clarification. Evidence access: Primary full text Fulvic acid attenuates homocysteine-induced cyclooxygenase-2 expression in human monocytes. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25888188/ · DOI 10.1186/s12906-015-0583-x
Complete structured claim and evidence
Fulvic pretreatment reduced PGE2 release after homocysteine stimulation.
Esther Material Technology fulvic preparation, 2015 study → Prostaglandin E2 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Human primary monocytes and U937 cells; Esther 20% stock diluted to 0.5-10 micrograms/mL, 4-hour pretreatment; homocysteine stimulation.
limitations
Cell exposure does not establish oral exposure, homocysteine removal or cardiovascular benefit. Results text reports homocysteine 200 micromolar, while figure captions say 200 micrograms/mL; dose units are unresolved. Inhibitor concentrations also need original-record clarification. This is not a demonstrated direct COX-2 catalytic inhibitor.
nutrient_topic
Fulvic acid collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Fulvic acid (heterogeneous humic fraction)
plain_language
The downstream prostaglandin output also fell.
primary_references
Fulvic acid attenuates homocysteine-induced cyclooxygenase-2 expression in human monocytes. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25888188/ · DOI 10.1186/s12906-015-0583-x
Fulvic acid: mixture identity, mineral chemistry, signaling and cross-nutrient mechanisms (2026-09-19) · lines 68–74
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human primary monocytes and U937 cells; Esther 20% stock diluted to 0.5-10 micrograms/mL, 4-hour pretreatment; homocysteine stimulation. · source_derived_draft · unverified_draft
## fulvic-acid-pge-output The downstream prostaglandin output also fell. Fulvic pretreatment reduced PGE2 release after homocysteine stimulation. Model: Human primary monocytes and U937 cells; Esther 20% stock diluted to 0.5-10 micrograms/mL, 4-hour pretreatment; homocysteine stimulation. Limitations: Cell exposure does not establish oral exposure, homocysteine removal or cardiovascular benefit. Results text reports homocysteine 200 micromolar, while figure captions say 200 micrograms/mL; dose units are unresolved. Inhibitor concentrations also need original-record clarification. This is not a demonstrated direct COX-2 catalytic inhibitor. Evidence access: Primary full text Fulvic acid attenuates homocysteine-induced cyclooxygenase-2 expression in human monocytes. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25888188/ · DOI 10.1186/s12906-015-0583-x
Complete structured claim and evidence
Dialysis and centrifugation showed copper association with the tested fulvic mixture.
Drinking-water fulvic mixture, 1999 copper study → Copper(II) ion source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Single oral radiocopper dose to 10-12-day-old rats; 0.93 mg Cu/L with 10 mg fulvic/L; chemical fractionation.
limitations
Binding is not evidence of improved systemic delivery.
nutrient_topic
Fulvic acid collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Fulvic acid (heterogeneous humic fraction)
plain_language
Copper can bind components of the mixture.
primary_references
Intestinal absorption of copper from drinking water containing fulvic acids and an infant formula mixture studied in a suckling rat model. · 1999 · https://pubmed.ncbi.nlm.nih.gov/10406087/ · DOI 10.1023/a:1009233802104
Fulvic acid: mixture identity, mineral chemistry, signaling and cross-nutrient mechanisms (2026-09-19) · lines 76–82
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Single oral radiocopper dose to 10-12-day-old rats; 0.93 mg Cu/L with 10 mg fulvic/L; chemical fractionation. · source_derived_draft · unverified_draft
## fulvic-acid-copper-binding Copper can bind components of the mixture. Dialysis and centrifugation showed copper association with the tested fulvic mixture. Model: Single oral radiocopper dose to 10-12-day-old rats; 0.93 mg Cu/L with 10 mg fulvic/L; chemical fractionation. Limitations: Binding is not evidence of improved systemic delivery. Evidence access: Primary abstract Intestinal absorption of copper from drinking water containing fulvic acids and an infant formula mixture studied in a suckling rat model. · 1999 · https://pubmed.ncbi.nlm.nih.gov/10406087/ · DOI 10.1023/a:1009233802104
Complete structured claim and evidence
Fulvic exposure increased intestinal mucosal copper retention at six hours without markedly changing lumen-to-mucosa uptake.
Drinking-water fulvic mixture, 1999 copper study → Rat intestinal copper retention after fulvic-mixture exposure source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Suckling-rat tracer study; water and formula matrices.
limitations
The abstract switches to Cd when describing circulatory absorption. That sentence is not silently treated as a verified copper result; no infant recommendation follows.
nutrient_topic
Fulvic acid collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Fulvic acid (heterogeneous humic fraction)
plain_language
Copper stayed in the intestinal lining longer.
primary_references
Intestinal absorption of copper from drinking water containing fulvic acids and an infant formula mixture studied in a suckling rat model. · 1999 · https://pubmed.ncbi.nlm.nih.gov/10406087/ · DOI 10.1023/a:1009233802104
Fulvic acid: mixture identity, mineral chemistry, signaling and cross-nutrient mechanisms (2026-09-19) · lines 84–90
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Suckling-rat tracer study; water and formula matrices. · source_derived_draft · unverified_draft
## fulvic-acid-copper-retention Copper stayed in the intestinal lining longer. Fulvic exposure increased intestinal mucosal copper retention at six hours without markedly changing lumen-to-mucosa uptake. Model: Suckling-rat tracer study; water and formula matrices. Limitations: The abstract switches to Cd when describing circulatory absorption. That sentence is not silently treated as a verified copper result; no infant recommendation follows. Evidence access: Primary abstract Intestinal absorption of copper from drinking water containing fulvic acids and an infant formula mixture studied in a suckling rat model. · 1999 · https://pubmed.ncbi.nlm.nih.gov/10406087/ · DOI 10.1023/a:1009233802104
Complete structured claim and evidence
The tested fulvic fraction formed iron(III) complexes within 15 minutes.
Fulvic fraction used in 2008 iron EXAFS study → Ferric iron source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Cell-free EXAFS spectroscopy; acidic aqueous solutions at pH 2 and 4.
limitations
Chemical binding does not establish human intestinal uptake or correction of iron deficiency.
nutrient_topic
Fulvic acid collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Fulvic acid (heterogeneous humic fraction)
plain_language
The organic fraction bound ferric iron.
primary_references
EXAFS study on the reactions between iron and fulvic acid in acid aqueous solutions. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18504967/ · DOI 10.1021/es072092z
Fulvic acid: mixture identity, mineral chemistry, signaling and cross-nutrient mechanisms (2026-09-19) · lines 92–98
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Cell-free EXAFS spectroscopy; acidic aqueous solutions at pH 2 and 4. · source_derived_draft · unverified_draft
## fulvic-acid-iron-complex The organic fraction bound ferric iron. The tested fulvic fraction formed iron(III) complexes within 15 minutes. Model: Cell-free EXAFS spectroscopy; acidic aqueous solutions at pH 2 and 4. Limitations: Chemical binding does not establish human intestinal uptake or correction of iron deficiency. Evidence access: Primary abstract EXAFS study on the reactions between iron and fulvic acid in acid aqueous solutions. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18504967/ · DOI 10.1021/es072092z
Complete structured claim and evidence
Iron(III) reduction to iron(II) occurred over time at pH 2 but was not significant at pH 4.
Fulvic fraction used in 2008 iron EXAFS study → Ferrous iron source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Cell-free EXAFS study of the specified fulvic fraction.
limitations
Stomach-like acidity alone does not reproduce food, digestion, mucosal transport or human pharmacokinetics.
nutrient_topic
Fulvic acid collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Fulvic acid (heterogeneous humic fraction)
plain_language
Acidity changed the iron-redox outcome.
primary_references
EXAFS study on the reactions between iron and fulvic acid in acid aqueous solutions. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18504967/ · DOI 10.1021/es072092z
Fulvic acid: mixture identity, mineral chemistry, signaling and cross-nutrient mechanisms (2026-09-19) · lines 100–106
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Cell-free EXAFS study of the specified fulvic fraction. · source_derived_draft · unverified_draft
## fulvic-acid-iron-redox Acidity changed the iron-redox outcome. Iron(III) reduction to iron(II) occurred over time at pH 2 but was not significant at pH 4. Model: Cell-free EXAFS study of the specified fulvic fraction. Limitations: Stomach-like acidity alone does not reproduce food, digestion, mucosal transport or human pharmacokinetics. Evidence access: Primary abstract EXAFS study on the reactions between iron and fulvic acid in acid aqueous solutions. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18504967/ · DOI 10.1021/es072092z
Complete structured claim and evidence
SS-FA at 0.1-10 micrograms/mL reduced PMA/calcium-ionophore-induced histamine release from KU812 cells.
Solubilized-sludge fulvic fraction, 2011 study → Histamine source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human basophilic leukemia KU812 cells; 15-minute pretreatment, PMA 20 nM plus A23187 1 micromolar.
limitations
Sludge-derived research material is not a dietary ingredient recommendation. This does not establish human allergy treatment or direct calcium chelation.
nutrient_topic
Fulvic acid collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Fulvic acid (heterogeneous humic fraction)
plain_language
One preparation reduced triggered mediator release.
primary_references
Microarray analysis of immediate-type allergy in KU812 cells in response to fulvic acid. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21331654/ · DOI 10.1007/s10616-010-9333-6
Fulvic acid: mixture identity, mineral chemistry, signaling and cross-nutrient mechanisms (2026-09-19) · lines 108–114
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human basophilic leukemia KU812 cells; 15-minute pretreatment, PMA 20 nM plus A23187 1 micromolar. · source_derived_draft · unverified_draft
## fulvic-acid-histamine One preparation reduced triggered mediator release. SS-FA at 0.1-10 micrograms/mL reduced PMA/calcium-ionophore-induced histamine release from KU812 cells. Model: Human basophilic leukemia KU812 cells; 15-minute pretreatment, PMA 20 nM plus A23187 1 micromolar. Limitations: Sludge-derived research material is not a dietary ingredient recommendation. This does not establish human allergy treatment or direct calcium chelation. Evidence access: Primary abstract Microarray analysis of immediate-type allergy in KU812 cells in response to fulvic acid. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21331654/ · DOI 10.1007/s10616-010-9333-6
Complete structured claim and evidence
SS-FA pretreatment altered allergy-associated transcripts in stimulated KU812 cells.
Solubilized-sludge fulvic fraction, 2011 study → KU812 allergy-related gene-expression profile after SS-FA source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human KU812 microarray study following PMA/calcium-ionophore stimulation.
limitations
Expression changes are not proof of direct receptor binding; cell-line results do not establish an oral dose.
nutrient_topic
Fulvic acid collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Fulvic acid (heterogeneous humic fraction)
plain_language
The cell response included changes in gene expression.
primary_references
Microarray analysis of immediate-type allergy in KU812 cells in response to fulvic acid. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21331654/ · DOI 10.1007/s10616-010-9333-6
Fulvic acid: mixture identity, mineral chemistry, signaling and cross-nutrient mechanisms (2026-09-19) · lines 116–122
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human KU812 microarray study following PMA/calcium-ionophore stimulation. · source_derived_draft · unverified_draft
## fulvic-acid-allergy-transcript The cell response included changes in gene expression. SS-FA pretreatment altered allergy-associated transcripts in stimulated KU812 cells. Model: Human KU812 microarray study following PMA/calcium-ionophore stimulation. Limitations: Expression changes are not proof of direct receptor binding; cell-line results do not establish an oral dose. Evidence access: Primary abstract Microarray analysis of immediate-type allergy in KU812 cells in response to fulvic acid. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21331654/ · DOI 10.1007/s10616-010-9333-6
Complete structured claim and evidence
CHD-FA exposure increased membrane permeability in Candida albicans assays.
Carbohydrate-derived fulvic acid / CHD-FA (preparation class) → Candida albicans membrane integrity source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Clinical Candida isolate panel; planktonic and biofilm growth; inhibitory concentrations reported as 0.125% and 0.25%.
limitations
An in-vitro antiseptic concentration is not a systemic supplement exposure or demonstrated infection treatment.
nutrient_topic
Fulvic acid collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Fulvic acid (heterogeneous humic fraction)
plain_language
The tested antifungal action involved a leaky membrane.
primary_references
Carbohydrate Derived Fulvic Acid: An in vitro Investigation of a Novel Membrane Active Antiseptic Agent Against Candida albicans Biofilms. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22479260/ · DOI 10.3389/fmicb.2012.00116
Fulvic acid: mixture identity, mineral chemistry, signaling and cross-nutrient mechanisms (2026-09-19) · lines 124–130
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Clinical Candida isolate panel; planktonic and biofilm growth; inhibitory concentrations reported as 0.125% and 0.25%. · source_derived_draft · unverified_draft
## fulvic-acid-fungal-membrane The tested antifungal action involved a leaky membrane. CHD-FA exposure increased membrane permeability in Candida albicans assays. Model: Clinical Candida isolate panel; planktonic and biofilm growth; inhibitory concentrations reported as 0.125% and 0.25%. Limitations: An in-vitro antiseptic concentration is not a systemic supplement exposure or demonstrated infection treatment. Evidence access: Primary full text Carbohydrate Derived Fulvic Acid: An in vitro Investigation of a Novel Membrane Active Antiseptic Agent Against Candida albicans Biofilms. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22479260/ · DOI 10.3389/fmicb.2012.00116
Complete structured claim and evidence
CHD-FA exposure caused extracellular ATP leakage from Candida cells.
Carbohydrate-derived fulvic acid / CHD-FA (preparation class) → ATP source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Candida membrane-permeability assay; ATP release followed over time.
limitations
ATP leakage indicates microbial membrane damage, not increased host ATP production.
nutrient_topic
Fulvic acid collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Fulvic acid (heterogeneous humic fraction)
plain_language
Cell contents escaped after membrane injury.
primary_references
Carbohydrate Derived Fulvic Acid: An in vitro Investigation of a Novel Membrane Active Antiseptic Agent Against Candida albicans Biofilms. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22479260/ · DOI 10.3389/fmicb.2012.00116
Fulvic acid: mixture identity, mineral chemistry, signaling and cross-nutrient mechanisms (2026-09-19) · lines 132–138
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Candida membrane-permeability assay; ATP release followed over time. · source_derived_draft · unverified_draft
## fulvic-acid-fungal-atp Cell contents escaped after membrane injury. CHD-FA exposure caused extracellular ATP leakage from Candida cells. Model: Candida membrane-permeability assay; ATP release followed over time. Limitations: ATP leakage indicates microbial membrane damage, not increased host ATP production. Evidence access: Primary full text Carbohydrate Derived Fulvic Acid: An in vitro Investigation of a Novel Membrane Active Antiseptic Agent Against Candida albicans Biofilms. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22479260/ · DOI 10.3389/fmicb.2012.00116
Complete structured claim and evidence
Chitin-synthesis inhibition with nikkomycin Z increased Candida susceptibility to CHD-FA.
Nikkomycin Z → Candida susceptibility to CHD-FA source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Candida planktonic and biofilm combination experiments.
limitations
This supports a cell-envelope mechanism; it is not a clinically established combination.
nutrient_topic
Fulvic acid collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Fulvic acid (heterogeneous humic fraction)
plain_language
Weakening the wall made the tested membrane-active exposure more effective.
primary_references
Carbohydrate Derived Fulvic Acid: An in vitro Investigation of a Novel Membrane Active Antiseptic Agent Against Candida albicans Biofilms. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22479260/ · DOI 10.3389/fmicb.2012.00116
Fulvic acid: mixture identity, mineral chemistry, signaling and cross-nutrient mechanisms (2026-09-19) · lines 140–146
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Candida planktonic and biofilm combination experiments. · source_derived_draft · unverified_draft
## fulvic-acid-fungal-chitin Weakening the wall made the tested membrane-active exposure more effective. Chitin-synthesis inhibition with nikkomycin Z increased Candida susceptibility to CHD-FA. Model: Candida planktonic and biofilm combination experiments. Limitations: This supports a cell-envelope mechanism; it is not a clinically established combination. Evidence access: Primary full text Carbohydrate Derived Fulvic Acid: An in vitro Investigation of a Novel Membrane Active Antiseptic Agent Against Candida albicans Biofilms. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22479260/ · DOI 10.3389/fmicb.2012.00116
Complete structured claim and evidence
The tested fulvic preparation reduced tau filament formation in vitro.
Fulvic preparation in 2011 tau study, identity unresolved here → Tau paired-helical-filament assembly in vitro source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Cell-free tau aggregation and atomic-force microscopy.
limitations
Preparation identity and concentration are not resolved from the accessed abstract; no brain delivery or Alzheimer efficacy is demonstrated.
nutrient_topic
Fulvic acid collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Fulvic acid (heterogeneous humic fraction)
plain_language
One preparation interfered with fibril assembly.
primary_references
Fulvic acid inhibits aggregation and promotes disassembly of tau fibrils associated with Alzheimer's disease. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21785188/ · DOI 10.3233/JAD-2011-110623
Fulvic acid: mixture identity, mineral chemistry, signaling and cross-nutrient mechanisms (2026-09-19) · lines 148–154
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Cell-free tau aggregation and atomic-force microscopy. · source_derived_draft · unverified_draft
## fulvic-acid-tau-assembly One preparation interfered with fibril assembly. The tested fulvic preparation reduced tau filament formation in vitro. Model: Cell-free tau aggregation and atomic-force microscopy. Limitations: Preparation identity and concentration are not resolved from the accessed abstract; no brain delivery or Alzheimer efficacy is demonstrated. Evidence access: Primary abstract Fulvic acid inhibits aggregation and promotes disassembly of tau fibrils associated with Alzheimer's disease. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21785188/ · DOI 10.3233/JAD-2011-110623
Complete structured claim and evidence
Exposure altered preformed tau fibrils, including shorter filaments.
Fulvic preparation in 2011 tau study, identity unresolved here → Preformed tau paired-helical-filament length and morphology source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Cell-free atomic-force microscopy.
limitations
Proposed hydrophobic interaction is not a verified binding site; smaller structures need not be non-toxic.
nutrient_topic
Fulvic acid collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Fulvic acid (heterogeneous humic fraction)
plain_language
Already formed fibrils changed in the assay.
primary_references
Fulvic acid inhibits aggregation and promotes disassembly of tau fibrils associated with Alzheimer's disease. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21785188/ · DOI 10.3233/JAD-2011-110623
Fulvic acid: mixture identity, mineral chemistry, signaling and cross-nutrient mechanisms (2026-09-19) · lines 156–162
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Cell-free atomic-force microscopy. · source_derived_draft · unverified_draft
## fulvic-acid-tau-disassembly Already formed fibrils changed in the assay. Exposure altered preformed tau fibrils, including shorter filaments. Model: Cell-free atomic-force microscopy. Limitations: Proposed hydrophobic interaction is not a verified binding site; smaller structures need not be non-toxic. Evidence access: Primary abstract Fulvic acid inhibits aggregation and promotes disassembly of tau fibrils associated with Alzheimer's disease. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21785188/ · DOI 10.3233/JAD-2011-110623
Complete structured claim and evidence
The specified reagent reduced K18 tau aggregation in RT-QuIC assays.
Defined fungal fulvic acid / CAS 479-66-3 → Human tau K18 amplification assay source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
2020 study; Cayman CAS 479-66-3 at 37 micromolar; HEK293 constructs or purified K18 tau as specified.
limitations
The methods identify a defined fungal compound, not an interchangeable environmental mixture. Supplier identity: https://www.caymanchem.com/product/19063/fulvic-acid . No clinical efficacy or CNS exposure was measured.
nutrient_topic
Fulvic acid collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Fulvic acid (heterogeneous humic fraction)
plain_language
The defined research chemical slowed an in-vitro aggregation readout.
primary_references
Effects of pharmacological modulators of α-synuclein and tau aggregation and internalization. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32732936/ · DOI 10.1038/s41598-020-69744-y
Fulvic acid: mixture identity, mineral chemistry, signaling and cross-nutrient mechanisms (2026-09-19) · lines 164–170
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · 2020 study; Cayman CAS 479-66-3 at 37 micromolar; HEK293 constructs or purified K18 tau as specified. · source_derived_draft · unverified_draft
## fulvic-acid-defined-tau-k18 The defined research chemical slowed an in-vitro aggregation readout. The specified reagent reduced K18 tau aggregation in RT-QuIC assays. Model: 2020 study; Cayman CAS 479-66-3 at 37 micromolar; HEK293 constructs or purified K18 tau as specified. Limitations: The methods identify a defined fungal compound, not an interchangeable environmental mixture. Supplier identity: https://www.caymanchem.com/product/19063/fulvic-acid . No clinical efficacy or CNS exposure was measured. Evidence access: Primary full text Effects of pharmacological modulators of α-synuclein and tau aggregation and internalization. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32732936/ · DOI 10.1038/s41598-020-69744-y
Complete structured claim and evidence
The reagent reduced tau HTRF aggregation signals, while tau BiFC-positive cell frequency was unchanged.
Defined fungal fulvic acid / CAS 479-66-3 → Tau aggregation readouts in human HEK293 cells source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
2020 study; Cayman CAS 479-66-3 at 37 micromolar; HEK293 constructs or purified K18 tau as specified. Twelve-hour treatment following co-culture.
limitations
The methods identify a defined fungal compound, not an interchangeable environmental mixture. Supplier identity: https://www.caymanchem.com/product/19063/fulvic-acid . No clinical efficacy or CNS exposure was measured. Assay differences are retained rather than collapsed into universal suppression.
nutrient_topic
Fulvic acid collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Fulvic acid (heterogeneous humic fraction)
plain_language
Two assays measured different aspects of the tau response.
primary_references
Effects of pharmacological modulators of α-synuclein and tau aggregation and internalization. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32732936/ · DOI 10.1038/s41598-020-69744-y
Fulvic acid: mixture identity, mineral chemistry, signaling and cross-nutrient mechanisms (2026-09-19) · lines 172–178
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · 2020 study; Cayman CAS 479-66-3 at 37 micromolar; HEK293 constructs or purified K18 tau as specified. Twelve-hour treatment following co-culture. · source_derived_draft · unverified_draft
## fulvic-acid-defined-cell-tau Two assays measured different aspects of the tau response. The reagent reduced tau HTRF aggregation signals, while tau BiFC-positive cell frequency was unchanged. Model: 2020 study; Cayman CAS 479-66-3 at 37 micromolar; HEK293 constructs or purified K18 tau as specified. Twelve-hour treatment following co-culture. Limitations: The methods identify a defined fungal compound, not an interchangeable environmental mixture. Supplier identity: https://www.caymanchem.com/product/19063/fulvic-acid . No clinical efficacy or CNS exposure was measured. Assay differences are retained rather than collapsed into universal suppression. Evidence access: Primary full text Effects of pharmacological modulators of α-synuclein and tau aggregation and internalization. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32732936/ · DOI 10.1038/s41598-020-69744-y
Complete structured claim and evidence
The reagent reduced alpha-synuclein aggregation signals in co-cultures; proteinase-K resistance was not significantly reduced in transfected-only cells.
Defined fungal fulvic acid / CAS 479-66-3 → Alpha-synuclein aggregation in human HEK293 co-cultures source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
2020 study; Cayman CAS 479-66-3 at 37 micromolar; HEK293 constructs or purified K18 tau as specified.
limitations
The methods identify a defined fungal compound, not an interchangeable environmental mixture. Supplier identity: https://www.caymanchem.com/product/19063/fulvic-acid . No clinical efficacy or CNS exposure was measured. Disassembly of all pre-existing alpha-synuclein aggregates was not established.
nutrient_topic
Fulvic acid collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Fulvic acid (heterogeneous humic fraction)
plain_language
The effect depended on how aggregates were produced and measured.
primary_references
Effects of pharmacological modulators of α-synuclein and tau aggregation and internalization. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32732936/ · DOI 10.1038/s41598-020-69744-y
Fulvic acid: mixture identity, mineral chemistry, signaling and cross-nutrient mechanisms (2026-09-19) · lines 180–186
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · 2020 study; Cayman CAS 479-66-3 at 37 micromolar; HEK293 constructs or purified K18 tau as specified. · source_derived_draft · unverified_draft
## fulvic-acid-defined-synuclein The effect depended on how aggregates were produced and measured. The reagent reduced alpha-synuclein aggregation signals in co-cultures; proteinase-K resistance was not significantly reduced in transfected-only cells. Model: 2020 study; Cayman CAS 479-66-3 at 37 micromolar; HEK293 constructs or purified K18 tau as specified. Limitations: The methods identify a defined fungal compound, not an interchangeable environmental mixture. Supplier identity: https://www.caymanchem.com/product/19063/fulvic-acid . No clinical efficacy or CNS exposure was measured. Disassembly of all pre-existing alpha-synuclein aggregates was not established. Evidence access: Primary full text Effects of pharmacological modulators of α-synuclein and tau aggregation and internalization. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32732936/ · DOI 10.1038/s41598-020-69744-y
Complete structured claim and evidence
Podzol-derived fulvic material increased respiration in isolated rat liver mitochondria.
Podzol-derived fulvic fraction, 1987 study → Rat liver mitochondrial respiration after podzol fulvic exposure source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
In-vitro mitochondrial exposure, 40-360 mg/L; lower-molecular-weight fractions had larger effects.
limitations
No oral pharmacokinetics or human ATP benefit is demonstrated. The abstract groups humic substances when describing phosphorylation efficiency, so a fulvic-specific efficiency claim is not inferred.
nutrient_topic
Fulvic acid collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Fulvic acid (heterogeneous humic fraction)
plain_language
A soil-derived fraction changed respiration in isolated organelles.
primary_references
Effect of humic substances on mitochondrial respiration and oxidative phosphorylation. · 1987 · https://pubmed.ncbi.nlm.nih.gov/2953069/ · DOI 10.1016/0048-9697(87)90521-3
Fulvic acid: mixture identity, mineral chemistry, signaling and cross-nutrient mechanisms (2026-09-19) · lines 188–194
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · In-vitro mitochondrial exposure, 40-360 mg/L; lower-molecular-weight fractions had larger effects. · source_derived_draft · unverified_draft
## fulvic-acid-mitochondrial-respiration A soil-derived fraction changed respiration in isolated organelles. Podzol-derived fulvic material increased respiration in isolated rat liver mitochondria. Model: In-vitro mitochondrial exposure, 40-360 mg/L; lower-molecular-weight fractions had larger effects. Limitations: No oral pharmacokinetics or human ATP benefit is demonstrated. The abstract groups humic substances when describing phosphorylation efficiency, so a fulvic-specific efficiency claim is not inferred. Evidence access: Primary abstract Effect of humic substances on mitochondrial respiration and oxidative phosphorylation. · 1987 · https://pubmed.ncbi.nlm.nih.gov/2953069/ · DOI 10.1016/0048-9697(87)90521-3
Complete structured claim and evidence
FulvoFeed at 5 or 50 mg C/L reduced the subsequent copper-associated ROS response.
FulvoFeed phenol-rich fulvic preparation, 2022 study → Copper-associated ROS fluorescence in zebrafish larvae source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Zebrafish larvae; FulvoFeed for 96 hours, wash, then copper 50 micromolar for 2 hours; ROS fluorescence assay.
limitations
mg C/L expresses organic carbon, not supplement mass. Washing reduced direct external copper-complexation confounding. ROS is an indirect inflammatory endpoint; proposed radical/aromatic explanations were not isolated genetic or binding tests.
nutrient_topic
Fulvic acid collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Fulvic acid (heterogeneous humic fraction)
plain_language
Lower tested exposures dampened the stress readout.
primary_references
Modification of the chemically induced inflammation assay reveals the Janus face of a phenol rich fulvic acid. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35393468/ · DOI 10.1038/s41598-022-09782-w
Fulvic acid: mixture identity, mineral chemistry, signaling and cross-nutrient mechanisms (2026-09-19) · lines 196–202
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Zebrafish larvae; FulvoFeed for 96 hours, wash, then copper 50 micromolar for 2 hours; ROS fluorescence assay. · source_derived_draft · unverified_draft
## fulvic-acid-zebrafish-low Lower tested exposures dampened the stress readout. FulvoFeed at 5 or 50 mg C/L reduced the subsequent copper-associated ROS response. Model: Zebrafish larvae; FulvoFeed for 96 hours, wash, then copper 50 micromolar for 2 hours; ROS fluorescence assay. Limitations: mg C/L expresses organic carbon, not supplement mass. Washing reduced direct external copper-complexation confounding. ROS is an indirect inflammatory endpoint; proposed radical/aromatic explanations were not isolated genetic or binding tests. Evidence access: Primary full text Modification of the chemically induced inflammation assay reveals the Janus face of a phenol rich fulvic acid. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35393468/ · DOI 10.1038/s41598-022-09782-w
Complete structured claim and evidence
FulvoFeed at 300 or 500 mg C/L increased the subsequent copper-associated ROS response.
FulvoFeed phenol-rich fulvic preparation, 2022 study → Copper-associated ROS fluorescence in zebrafish larvae source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Zebrafish larvae; FulvoFeed for 96 hours, wash, then copper 50 micromolar for 2 hours; ROS fluorescence assay.
limitations
mg C/L expresses organic carbon, not supplement mass. Washing reduced direct external copper-complexation confounding. ROS is an indirect inflammatory endpoint; proposed radical/aromatic explanations were not isolated genetic or binding tests. This is a concentration-dependent result, not an unexplained contradiction with the lower-dose result.
nutrient_topic
Fulvic acid collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Fulvic acid (heterogeneous humic fraction)
plain_language
Higher tested exposures amplified the same stress readout.
primary_references
Modification of the chemically induced inflammation assay reveals the Janus face of a phenol rich fulvic acid. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35393468/ · DOI 10.1038/s41598-022-09782-w
Fulvic acid: mixture identity, mineral chemistry, signaling and cross-nutrient mechanisms (2026-09-19) · lines 204–210
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Zebrafish larvae; FulvoFeed for 96 hours, wash, then copper 50 micromolar for 2 hours; ROS fluorescence assay. · source_derived_draft · unverified_draft
## fulvic-acid-zebrafish-high Higher tested exposures amplified the same stress readout. FulvoFeed at 300 or 500 mg C/L increased the subsequent copper-associated ROS response. Model: Zebrafish larvae; FulvoFeed for 96 hours, wash, then copper 50 micromolar for 2 hours; ROS fluorescence assay. Limitations: mg C/L expresses organic carbon, not supplement mass. Washing reduced direct external copper-complexation confounding. ROS is an indirect inflammatory endpoint; proposed radical/aromatic explanations were not isolated genetic or binding tests. This is a concentration-dependent result, not an unexplained contradiction with the lower-dose result. Evidence access: Primary full text Modification of the chemically induced inflammation assay reveals the Janus face of a phenol rich fulvic acid. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35393468/ · DOI 10.1038/s41598-022-09782-w
Complete structured claim and evidence
Reference fulvic fractions increased iron import in respiratory epithelial cells.
Suwannee River fulvic acid reference material → Iron import in fulvic-exposed respiratory epithelial cells source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human respiratory epithelial-cell exposure to Suwannee River/Nordic reference fulvic fractions; comparison with smoke water-soluble fractions.
limitations
Abstract access; exposure concentration and duration require full-method verification. Increased iron import is consistent with compensatory iron stress, not direct quantification of every intracellular available-iron pool. These are airway-cell exposures, not an oral trial.
nutrient_topic
Fulvic acid collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Fulvic acid (heterogeneous humic fraction)
plain_language
Cells changed their iron handling after direct exposure.
primary_references
A Fulvic Acid-like Substance Participates in the Pro-inflammatory Effects of Cigarette Smoke and Wood Smoke Particles. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32191033/ · DOI 10.1021/acs.chemrestox.0c00036
Fulvic acid: mixture identity, mineral chemistry, signaling and cross-nutrient mechanisms (2026-09-19) · lines 212–218
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human respiratory epithelial-cell exposure to Suwannee River/Nordic reference fulvic fractions; comparison with smoke water-soluble fractions. · source_derived_draft · unverified_draft
## fulvic-acid-airway-iron-import Cells changed their iron handling after direct exposure. Reference fulvic fractions increased iron import in respiratory epithelial cells. Model: Human respiratory epithelial-cell exposure to Suwannee River/Nordic reference fulvic fractions; comparison with smoke water-soluble fractions. Limitations: Abstract access; exposure concentration and duration require full-method verification. Increased iron import is consistent with compensatory iron stress, not direct quantification of every intracellular available-iron pool. These are airway-cell exposures, not an oral trial. Evidence access: Primary abstract A Fulvic Acid-like Substance Participates in the Pro-inflammatory Effects of Cigarette Smoke and Wood Smoke Particles. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32191033/ · DOI 10.1021/acs.chemrestox.0c00036
Complete structured claim and evidence
Reference fulvic fractions increased IL-6 and IL-8 release from respiratory epithelial cells.
Suwannee River fulvic acid reference material → IL6 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human respiratory epithelial-cell exposure to Suwannee River/Nordic reference fulvic fractions; comparison with smoke water-soluble fractions.
limitations
Abstract access; exposure concentration and duration require full-method verification. Increased iron import is consistent with compensatory iron stress, not direct quantification of every intracellular available-iron pool. These are airway-cell exposures, not an oral trial.
nutrient_topic
Fulvic acid collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Fulvic acid (heterogeneous humic fraction)
plain_language
Direct airway-cell exposure stimulated inflammatory mediators.
primary_references
A Fulvic Acid-like Substance Participates in the Pro-inflammatory Effects of Cigarette Smoke and Wood Smoke Particles. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32191033/ · DOI 10.1021/acs.chemrestox.0c00036
Fulvic acid: mixture identity, mineral chemistry, signaling and cross-nutrient mechanisms (2026-09-19) · lines 220–226
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human respiratory epithelial-cell exposure to Suwannee River/Nordic reference fulvic fractions; comparison with smoke water-soluble fractions. · source_derived_draft · unverified_draft
## fulvic-acid-airway-inflammation Direct airway-cell exposure stimulated inflammatory mediators. Reference fulvic fractions increased IL-6 and IL-8 release from respiratory epithelial cells. Model: Human respiratory epithelial-cell exposure to Suwannee River/Nordic reference fulvic fractions; comparison with smoke water-soluble fractions. Limitations: Abstract access; exposure concentration and duration require full-method verification. Increased iron import is consistent with compensatory iron stress, not direct quantification of every intracellular available-iron pool. These are airway-cell exposures, not an oral trial. Evidence access: Primary abstract A Fulvic Acid-like Substance Participates in the Pro-inflammatory Effects of Cigarette Smoke and Wood Smoke Particles. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32191033/ · DOI 10.1021/acs.chemrestox.0c00036
Complete structured claim and evidence
Iron co-exposure reduced fulvic-associated IL-6/IL-8 release in the tested cells.
Iron → Cytokine release after reference fulvic exposure in airway cells source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human respiratory epithelial-cell exposure to Suwannee River/Nordic reference fulvic fractions; comparison with smoke water-soluble fractions.
limitations
Abstract access; exposure concentration and duration require full-method verification. Increased iron import is consistent with compensatory iron stress, not direct quantification of every intracellular available-iron pool. These are airway-cell exposures, not an oral trial. This is not a recommendation to supplement iron or proof of systemic iron deficiency.
nutrient_topic
Fulvic acid collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Fulvic acid (heterogeneous humic fraction)
plain_language
Adding iron altered the inflammatory response in this experiment.
primary_references
A Fulvic Acid-like Substance Participates in the Pro-inflammatory Effects of Cigarette Smoke and Wood Smoke Particles. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32191033/ · DOI 10.1021/acs.chemrestox.0c00036
Fulvic acid: mixture identity, mineral chemistry, signaling and cross-nutrient mechanisms (2026-09-19) · lines 228–234
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human respiratory epithelial-cell exposure to Suwannee River/Nordic reference fulvic fractions; comparison with smoke water-soluble fractions. · source_derived_draft · unverified_draft
## fulvic-acid-airway-iron-rescue Adding iron altered the inflammatory response in this experiment. Iron co-exposure reduced fulvic-associated IL-6/IL-8 release in the tested cells. Model: Human respiratory epithelial-cell exposure to Suwannee River/Nordic reference fulvic fractions; comparison with smoke water-soluble fractions. Limitations: Abstract access; exposure concentration and duration require full-method verification. Increased iron import is consistent with compensatory iron stress, not direct quantification of every intracellular available-iron pool. These are airway-cell exposures, not an oral trial. This is not a recommendation to supplement iron or proof of systemic iron deficiency. Evidence access: Primary abstract A Fulvic Acid-like Substance Participates in the Pro-inflammatory Effects of Cigarette Smoke and Wood Smoke Particles. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32191033/ · DOI 10.1021/acs.chemrestox.0c00036
Complete structured claim and evidence
MLG formulations reduced the LPS-induced reporter response.
MLG-50 fossil-derived fulvic/mineral formulation → LPS-induced NF-kappa-B reporter response in human THP1-Blue cells source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
2026 MLG-50/MLG-A50 study; fossil extracts contain fulvic fractions plus mineral/polyphenol components, stock pH about 1.97/12.1. THP1-Blue cells; 1:8192 dilution, LPS 10 or 50 ng/mL, 24 hours.
limitations
Co-components prevent assigning an effect to a single fulvic molecule. In-vitro activity is not established clinical benefit; preparation and dilution remain essential. LPS interaction and receptor interference are proposed from functional assays; direct TLR4 binding is not established.
nutrient_topic
Fulvic acid collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Fulvic acid (heterogeneous humic fraction)
plain_language
The mixtures changed the response to bacterial endotoxin.
primary_references
Integrated safety and microbiota profiling of fulvic acid formulations across in vitro and in vivo models. · 2026 · https://pubmed.ncbi.nlm.nih.gov/41580488/ · DOI 10.1038/s41598-026-37331-2
Fulvic acid: mixture identity, mineral chemistry, signaling and cross-nutrient mechanisms (2026-09-19) · lines 236–242
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · 2026 MLG-50/MLG-A50 study; fossil extracts contain fulvic fractions plus mineral/polyphenol components, stock pH about 1.97/12.1. THP1-Blue cells; 1:8192 dilution, LPS 10 or 50 ng/mL, 24 hours. · source_derived_draft · unverified_draft
## fulvic-acid-lps-signal The mixtures changed the response to bacterial endotoxin. MLG formulations reduced the LPS-induced reporter response. Model: 2026 MLG-50/MLG-A50 study; fossil extracts contain fulvic fractions plus mineral/polyphenol components, stock pH about 1.97/12.1. THP1-Blue cells; 1:8192 dilution, LPS 10 or 50 ng/mL, 24 hours. Limitations: Co-components prevent assigning an effect to a single fulvic molecule. In-vitro activity is not established clinical benefit; preparation and dilution remain essential. LPS interaction and receptor interference are proposed from functional assays; direct TLR4 binding is not established. Evidence access: Primary full text Integrated safety and microbiota profiling of fulvic acid formulations across in vitro and in vivo models. · 2026 · https://pubmed.ncbi.nlm.nih.gov/41580488/ · DOI 10.1038/s41598-026-37331-2
Complete structured claim and evidence
MLG-A50 increased scratch closure in LoVo-cell assays.
MLG-A50 alkaline fulvic/mineral formulation → Human LoVo scratch-assay closure under fulvic formulation exposure source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
2026 MLG-50/MLG-A50 study; fossil extracts contain fulvic fractions plus mineral/polyphenol components, stock pH about 1.97/12.1. Human colorectal adenocarcinoma LoVo cells; dilutions 1:8192 to 1:32768.
limitations
Co-components prevent assigning an effect to a single fulvic molecule. In-vitro activity is not established clinical benefit; preparation and dilution remain essential. This cancer-cell assay does not establish healthy intestinal repair or barrier integrity.
nutrient_topic
Fulvic acid collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Fulvic acid (heterogeneous humic fraction)
plain_language
A cultured monolayer closed its artificial gap faster.
primary_references
Integrated safety and microbiota profiling of fulvic acid formulations across in vitro and in vivo models. · 2026 · https://pubmed.ncbi.nlm.nih.gov/41580488/ · DOI 10.1038/s41598-026-37331-2
Fulvic acid: mixture identity, mineral chemistry, signaling and cross-nutrient mechanisms (2026-09-19) · lines 244–250
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · 2026 MLG-50/MLG-A50 study; fossil extracts contain fulvic fractions plus mineral/polyphenol components, stock pH about 1.97/12.1. Human colorectal adenocarcinoma LoVo cells; dilutions 1:8192 to 1:32768. · source_derived_draft · unverified_draft
## fulvic-acid-lovo-scratch A cultured monolayer closed its artificial gap faster. MLG-A50 increased scratch closure in LoVo-cell assays. Model: 2026 MLG-50/MLG-A50 study; fossil extracts contain fulvic fractions plus mineral/polyphenol components, stock pH about 1.97/12.1. Human colorectal adenocarcinoma LoVo cells; dilutions 1:8192 to 1:32768. Limitations: Co-components prevent assigning an effect to a single fulvic molecule. In-vitro activity is not established clinical benefit; preparation and dilution remain essential. This cancer-cell assay does not establish healthy intestinal repair or barrier integrity. Evidence access: Primary full text Integrated safety and microbiota profiling of fulvic acid formulations across in vitro and in vivo models. · 2026 · https://pubmed.ncbi.nlm.nih.gov/41580488/ · DOI 10.1038/s41598-026-37331-2
Complete structured claim and evidence
Oral MLG formulations changed measured fecal microbiota composition and diversity in guinea pigs.
MLG-50 fossil-derived fulvic/mineral formulation → Guinea-pig fecal microbial community after fulvic formulations source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
2026 MLG-50/MLG-A50 study; fossil extracts contain fulvic fractions plus mineral/polyphenol components, stock pH about 1.97/12.1. Preliminary groups n=8; oral 0.65 mg/kg twice daily for 21 days.
limitations
Co-components prevent assigning an effect to a single fulvic molecule. In-vitro activity is not established clinical benefit; preparation and dilution remain essential. Taxon abundance does not prove beneficial function, nutrient synthesis or improved human health; exploratory comparisons have multiplicity limitations.
nutrient_topic
Fulvic acid collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Fulvic acid (heterogeneous humic fraction)
plain_language
The preparations altered microbial-community measurements.
primary_references
Integrated safety and microbiota profiling of fulvic acid formulations across in vitro and in vivo models. · 2026 · https://pubmed.ncbi.nlm.nih.gov/41580488/ · DOI 10.1038/s41598-026-37331-2
Fulvic acid: mixture identity, mineral chemistry, signaling and cross-nutrient mechanisms (2026-09-19) · lines 252–258
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · 2026 MLG-50/MLG-A50 study; fossil extracts contain fulvic fractions plus mineral/polyphenol components, stock pH about 1.97/12.1. Preliminary groups n=8; oral 0.65 mg/kg twice daily for 21 days. · source_derived_draft · unverified_draft
## fulvic-acid-guinea-pig-microbiota The preparations altered microbial-community measurements. Oral MLG formulations changed measured fecal microbiota composition and diversity in guinea pigs. Model: 2026 MLG-50/MLG-A50 study; fossil extracts contain fulvic fractions plus mineral/polyphenol components, stock pH about 1.97/12.1. Preliminary groups n=8; oral 0.65 mg/kg twice daily for 21 days. Limitations: Co-components prevent assigning an effect to a single fulvic molecule. In-vitro activity is not established clinical benefit; preparation and dilution remain essential. Taxon abundance does not prove beneficial function, nutrient synthesis or improved human health; exploratory comparisons have multiplicity limitations. Evidence access: Primary full text Integrated safety and microbiota profiling of fulvic acid formulations across in vitro and in vivo models. · 2026 · https://pubmed.ncbi.nlm.nih.gov/41580488/ · DOI 10.1038/s41598-026-37331-2
Complete structured claim and evidence
The small oral CHD-FA trial reported reduced skin-prick responses.
Carbohydrate-derived fulvic acid / CHD-FA (preparation class) → Skin-prick response in the CHD-FA atopy trial source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
30 atopic men; escalating exposure and crossover component, 3.8% solution up to 40 mL twice daily for one week.
limitations
Short duration and a surrogate endpoint do not establish treatment of allergic disease or effects of other preparations.
nutrient_topic
Fulvic acid collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Fulvic acid (heterogeneous humic fraction)
plain_language
An allergy-test response changed in a short trial.
primary_references
Phase 1 clinical study of the acute and subacute safety and proof-of-concept efficacy of carbohydrate-derived fulvic acid. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22427734/ · DOI 10.2147/CPAA.S25784
Fulvic acid: mixture identity, mineral chemistry, signaling and cross-nutrient mechanisms (2026-09-19) · lines 260–266
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · 30 atopic men; escalating exposure and crossover component, 3.8% solution up to 40 mL twice daily for one week. · source_derived_draft · unverified_draft
## fulvic-acid-human-atopy An allergy-test response changed in a short trial. The small oral CHD-FA trial reported reduced skin-prick responses. Model: 30 atopic men; escalating exposure and crossover component, 3.8% solution up to 40 mL twice daily for one week. Limitations: Short duration and a surrogate endpoint do not establish treatment of allergic disease or effects of other preparations. Evidence access: Primary abstract Phase 1 clinical study of the acute and subacute safety and proof-of-concept efficacy of carbohydrate-derived fulvic acid. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22427734/ · DOI 10.2147/CPAA.S25784
Complete structured claim and evidence
No severe adverse events were reported and measured safety parameters remained stable during the trial.
Carbohydrate-derived fulvic acid / CHD-FA (preparation class) → Short-term safety observations in the CHD-FA phase-1 trial source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
30 atopic male volunteers; acute/subacute escalating exposures and one-week crossover treatment.
limitations
Cannot establish chronic safety, pregnancy safety, safety in children, or equivalence of contaminated/environmental extracts.
nutrient_topic
Fulvic acid collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Fulvic acid (heterogeneous humic fraction)
plain_language
This specified preparation was monitored for a short period.
primary_references
Phase 1 clinical study of the acute and subacute safety and proof-of-concept efficacy of carbohydrate-derived fulvic acid. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22427734/ · DOI 10.2147/CPAA.S25784
Fulvic acid: mixture identity, mineral chemistry, signaling and cross-nutrient mechanisms (2026-09-19) · lines 268–274
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · 30 atopic male volunteers; acute/subacute escalating exposures and one-week crossover treatment. · source_derived_draft · unverified_draft
## fulvic-acid-human-short-safety This specified preparation was monitored for a short period. No severe adverse events were reported and measured safety parameters remained stable during the trial. Model: 30 atopic male volunteers; acute/subacute escalating exposures and one-week crossover treatment. Limitations: Cannot establish chronic safety, pregnancy safety, safety in children, or equivalence of contaminated/environmental extracts. Evidence access: Primary abstract Phase 1 clinical study of the acute and subacute safety and proof-of-concept efficacy of carbohydrate-derived fulvic acid. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22427734/ · DOI 10.2147/CPAA.S25784
Complete structured claim and evidence
Investigator global response favored topical CHD-FA over vehicle; several other measures improved in both groups.
Carbohydrate-derived fulvic acid / CHD-FA (preparation class) → Investigator global eczema response in topical CHD-FA trial source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
36 volunteers aged at least two years; twice-daily topical treatment for four weeks; randomized blinded study.
limitations
Small exploratory trial; do not convert within-group improvement into a between-group benefit. Transient burning occurred; topical results do not prove oral efficacy.
nutrient_topic
Fulvic acid collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Fulvic acid (heterogeneous humic fraction)
plain_language
One overall score favored the active topical preparation.
primary_references
Randomized, parallel-group, double-blind, controlled study to evaluate the efficacy and safety of carbohydrate-derived fulvic acid in topical treatment of eczema. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21931500/ · DOI 10.2147/CCID.S23110
Fulvic acid: mixture identity, mineral chemistry, signaling and cross-nutrient mechanisms (2026-09-19) · lines 276–282
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · 36 volunteers aged at least two years; twice-daily topical treatment for four weeks; randomized blinded study. · source_derived_draft · unverified_draft
## fulvic-acid-eczema One overall score favored the active topical preparation. Investigator global response favored topical CHD-FA over vehicle; several other measures improved in both groups. Model: 36 volunteers aged at least two years; twice-daily topical treatment for four weeks; randomized blinded study. Limitations: Small exploratory trial; do not convert within-group improvement into a between-group benefit. Transient burning occurred; topical results do not prove oral efficacy. Evidence access: Primary abstract Randomized, parallel-group, double-blind, controlled study to evaluate the efficacy and safety of carbohydrate-derived fulvic acid in topical treatment of eczema. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21931500/ · DOI 10.2147/CCID.S23110
Complete structured claim and evidence
CHD-FA did not produce a clear reproducible mutagenic response in the reported Ames tests.
Carbohydrate-derived fulvic acid / CHD-FA (preparation class) → Bacterial reverse-mutation results for CHD-FA source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Salmonella and E. coli assays with/without S9, up to 5000 micrograms/plate.
limitations
The 2026 study was electronically published June 21, with a December issue date. Negative results in one assay do not erase positive or uncertain findings in another; chronic exposure remains unresolved. High-dose toxicity and a doubtful TA1537 response were reported.
nutrient_topic
Fulvic acid collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Fulvic acid (heterogeneous humic fraction)
plain_language
Bacterial mutation testing was interpreted as negative.
primary_references
Genotoxicity of Carbohydrate Derived Fulvic Acid. · 2026 · https://pubmed.ncbi.nlm.nih.gov/42383226/ · DOI 10.1016/j.toxrep.2026.102298
Fulvic acid: mixture identity, mineral chemistry, signaling and cross-nutrient mechanisms (2026-09-19) · lines 284–290
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Salmonella and E. coli assays with/without S9, up to 5000 micrograms/plate. · source_derived_draft · unverified_draft
## fulvic-acid-ames Bacterial mutation testing was interpreted as negative. CHD-FA did not produce a clear reproducible mutagenic response in the reported Ames tests. Model: Salmonella and E. coli assays with/without S9, up to 5000 micrograms/plate. Limitations: The 2026 study was electronically published June 21, with a December issue date. Negative results in one assay do not erase positive or uncertain findings in another; chronic exposure remains unresolved. High-dose toxicity and a doubtful TA1537 response were reported. Evidence access: Primary full text Genotoxicity of Carbohydrate Derived Fulvic Acid. · 2026 · https://pubmed.ncbi.nlm.nih.gov/42383226/ · DOI 10.1016/j.toxrep.2026.102298
Complete structured claim and evidence
CHD-FA increased micronucleus frequency in human lymphocyte testing under growth-inhibiting conditions.
Carbohydrate-derived fulvic acid / CHD-FA (preparation class) → Human lymphocyte micronucleus frequency after CHD-FA source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
In-vitro lymphocyte assay with/without metabolic activation; acidic high-dose conditions.
limitations
The 2026 study was electronically published June 21, with a December issue date. Negative results in one assay do not erase positive or uncertain findings in another; chronic exposure remains unresolved. Acidity is a proposed explanation, not a demonstrated causal resolution; no mechanistic follow-up isolated it.
nutrient_topic
Fulvic acid collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Fulvic acid (heterogeneous humic fraction)
plain_language
One mammalian-cell test gave a positive signal.
primary_references
Genotoxicity of Carbohydrate Derived Fulvic Acid. · 2026 · https://pubmed.ncbi.nlm.nih.gov/42383226/ · DOI 10.1016/j.toxrep.2026.102298
Fulvic acid: mixture identity, mineral chemistry, signaling and cross-nutrient mechanisms (2026-09-19) · lines 292–298
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · In-vitro lymphocyte assay with/without metabolic activation; acidic high-dose conditions. · source_derived_draft · unverified_draft
## fulvic-acid-lymphocyte-micronuclei One mammalian-cell test gave a positive signal. CHD-FA increased micronucleus frequency in human lymphocyte testing under growth-inhibiting conditions. Model: In-vitro lymphocyte assay with/without metabolic activation; acidic high-dose conditions. Limitations: The 2026 study was electronically published June 21, with a December issue date. Negative results in one assay do not erase positive or uncertain findings in another; chronic exposure remains unresolved. Acidity is a proposed explanation, not a demonstrated causal resolution; no mechanistic follow-up isolated it. Evidence access: Primary full text Genotoxicity of Carbohydrate Derived Fulvic Acid. · 2026 · https://pubmed.ncbi.nlm.nih.gov/42383226/ · DOI 10.1016/j.toxrep.2026.102298
Complete structured claim and evidence
CHD-FA did not significantly increase micronucleated polychromatic erythrocytes in tested mice.
Carbohydrate-derived fulvic acid / CHD-FA (preparation class) → Mouse erythrocyte micronuclei after CHD-FA source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Male mouse micronucleus assay; reported doses up to 100 mg/kg, sampling at 24/48 hours.
limitations
The 2026 study was electronically published June 21, with a December issue date. Negative results in one assay do not erase positive or uncertain findings in another; chronic exposure remains unresolved. Full results report reduced PCE/NCE at 100 mg/kg after 48 hours despite the abstract summary; retain this marrow-response finding.
nutrient_topic
Fulvic acid collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Fulvic acid (heterogeneous humic fraction)
plain_language
The mouse chromosomal-damage endpoint was negative.
primary_references
Genotoxicity of Carbohydrate Derived Fulvic Acid. · 2026 · https://pubmed.ncbi.nlm.nih.gov/42383226/ · DOI 10.1016/j.toxrep.2026.102298
Fulvic acid: mixture identity, mineral chemistry, signaling and cross-nutrient mechanisms (2026-09-19) · lines 300–306
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Male mouse micronucleus assay; reported doses up to 100 mg/kg, sampling at 24/48 hours. · source_derived_draft · unverified_draft
## fulvic-acid-mouse-micronuclei The mouse chromosomal-damage endpoint was negative. CHD-FA did not significantly increase micronucleated polychromatic erythrocytes in tested mice. Model: Male mouse micronucleus assay; reported doses up to 100 mg/kg, sampling at 24/48 hours. Limitations: The 2026 study was electronically published June 21, with a December issue date. Negative results in one assay do not erase positive or uncertain findings in another; chronic exposure remains unresolved. Full results report reduced PCE/NCE at 100 mg/kg after 48 hours despite the abstract summary; retain this marrow-response finding. Evidence access: Primary full text Genotoxicity of Carbohydrate Derived Fulvic Acid. · 2026 · https://pubmed.ncbi.nlm.nih.gov/42383226/ · DOI 10.1016/j.toxrep.2026.102298
Complete structured claim and evidence
Riboflavin lowered plasma homocysteine in the MTHFR 677TT group by 22% overall; the lower-baseline-B2 subgroup showed a 40% decrease.
Riboflavin (vitamin B2) → Homocysteine source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
B2 cofactor supply interacts with folate-cycle enzyme genotype.
experimental_model
Genotype-stratified randomized trial; 35 TT, 26 CT and 28 CC adults selected, ages 18-65.
exposure
1.6 mg/day riboflavin versus placebo for 12 weeks; experimental regimen.
genotype
MTHFR 677TT; common variant rather than complete loss of enzyme
limitations
Small genotype strata; subgroup magnitude is not an expected response for every TT carrier. The trial did not test cardiovascular events.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
In this trial, improving B2 supply lowered a folate-pathway blood marker in people with two copies of the studied MTHFR variant.
primary_references
[b2-mcnulty2006] Riboflavin lowers homocysteine in individuals homozygous for the MTHFR 677C->T polymorphism (2006). https://pubmed.ncbi.nlm.nih.gov/16380544/ DOI: 10.1161/circulationaha.105.580332
tissue_or_cell_type
Human clinical setting
trigger_kind
machinery_impairment Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1486–1498
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Genotype-stratified randomized trial; 35 TT, 26 CT and 28 CC adults selected, ages 18-65. · source_derived_draft · unverified_draft
### b2-tt-homocysteine-response Riboflavin lowered plasma homocysteine in the MTHFR 677TT group by 22% overall; the lower-baseline-B2 subgroup showed a 40% decrease. Condition category: machinery_impairment nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: In this trial, improving B2 supply lowered a folate-pathway blood marker in people with two copies of the studied MTHFR variant. organism: Homo sapiens tissue_or_cell_type: Human clinical setting experimental_model: Genotype-stratified randomized trial; 35 TT, 26 CT and 28 CC adults selected, ages 18-65. limitations: Small genotype strata; subgroup magnitude is not an expected response for every TT carrier. The trial did not test cardiovascular events. exposure: 1.6 mg/day riboflavin versus placebo for 12 weeks; experimental regimen. cross_nutrient: B2 cofactor supply interacts with folate-cycle enzyme genotype. genotype: MTHFR 677TT; common variant rather than complete loss of enzyme [b2-mcnulty2006] Riboflavin lowers homocysteine in individuals homozygous for the MTHFR 677C->T polymorphism (2006). https://pubmed.ncbi.nlm.nih.gov/16380544/ DOI: 10.1161/circulationaha.105.580332
Complete structured claim and evidence
No homocysteine response was observed in the CC or CT groups despite improved riboflavin-status measures in all genotype groups.
Riboflavin (vitamin B2) → Homocysteine source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Folate-cycle biomarker response was genotype dependent.
experimental_model
Genotype-stratified randomized trial; 35 TT, 26 CT and 28 CC adults selected, ages 18-65.
exposure
1.6 mg/day riboflavin versus placebo for 12 weeks; experimental regimen.
genotype
MTHFR 677CC or 677CT
limitations
Null findings in modest samples do not prove an effect is impossible; context differs from the TT arm.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
A better B2 test result did not automatically lower homocysteine in everyone.
primary_references
[b2-mcnulty2006] Riboflavin lowers homocysteine in individuals homozygous for the MTHFR 677C->T polymorphism (2006). https://pubmed.ncbi.nlm.nih.gov/16380544/ DOI: 10.1161/circulationaha.105.580332
tissue_or_cell_type
Human clinical setting
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1500–1512
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Genotype-stratified randomized trial; 35 TT, 26 CT and 28 CC adults selected, ages 18-65. · source_derived_draft · unverified_draft
### b2-cc-ct-homocysteine-nonresponse No homocysteine response was observed in the CC or CT groups despite improved riboflavin-status measures in all genotype groups. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A better B2 test result did not automatically lower homocysteine in everyone. organism: Homo sapiens tissue_or_cell_type: Human clinical setting experimental_model: Genotype-stratified randomized trial; 35 TT, 26 CT and 28 CC adults selected, ages 18-65. limitations: Null findings in modest samples do not prove an effect is impossible; context differs from the TT arm. exposure: 1.6 mg/day riboflavin versus placebo for 12 weeks; experimental regimen. cross_nutrient: Folate-cycle biomarker response was genotype dependent. genotype: MTHFR 677CC or 677CT [b2-mcnulty2006] Riboflavin lowers homocysteine in individuals homozygous for the MTHFR 677C->T polymorphism (2006). https://pubmed.ncbi.nlm.nih.gov/16380544/ DOI: 10.1161/circulationaha.105.580332
Complete structured claim and evidence
Controlled depletion lowered plasma folate and significantly raised plasma homocysteine in eight postmenopausal women.
Folate (vitamin B9) → Homocysteine source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
Folate and B12 meet at methionine synthase; this experiment manipulated folate intake.
experimental_model
Eight healthy postmenopausal women aged 49–63 in a metabolic unit, sequential depletion/repletion.
exposure
Five weeks 56 micrograms/day folate, four weeks 111, then three weeks 286–516 using folic acid added to a low-folate diet.
limitations
A concentration is not direct enzyme flux; B12 status, kidney function and other inputs also affect this marker.
nutrient_topic
Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. · Folate (vitamin B9)
organism
Homo sapiens
plain_language
A shortage made a connected methionine-recycling marker rise.
primary_references
[fol-jacob1998] Moderate folate depletion increases plasma homocysteine and decreases lymphocyte DNA methylation in postmenopausal women (1998). https://pubmed.ncbi.nlm.nih.gov/9649607/ DOI: 10.1093/jn/128.7.1204
tissue_or_cell_type
Human blood or whole-person clinical endpoints
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1408–1419
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Eight healthy postmenopausal women aged 49–63 in a metabolic unit, sequential depletion/repletion. · source_derived_draft · unverified_draft
### fol-depletion-homocysteine Controlled depletion lowered plasma folate and significantly raised plasma homocysteine in eight postmenopausal women. Condition category: nutrient_deficiency nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: A shortage made a connected methionine-recycling marker rise. organism: Homo sapiens tissue_or_cell_type: Human blood or whole-person clinical endpoints experimental_model: Eight healthy postmenopausal women aged 49–63 in a metabolic unit, sequential depletion/repletion. limitations: A concentration is not direct enzyme flux; B12 status, kidney function and other inputs also affect this marker. exposure: Five weeks 56 micrograms/day folate, four weeks 111, then three weeks 286–516 using folic acid added to a low-folate diet. cross_nutrient: Folate and B12 meet at methionine synthase; this experiment manipulated folate intake. [fol-jacob1998] Moderate folate depletion increases plasma homocysteine and decreases lymphocyte DNA methylation in postmenopausal women (1998). https://pubmed.ncbi.nlm.nih.gov/9649607/ DOI: 10.1093/jn/128.7.1204
Complete structured claim and evidence
Bhmt deletion raised hepatic total homocysteine sixfold and plasma total homocysteine eightfold in mice.
Bhmt gene (Mus musculus) → Homocysteine source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
Loss of betaine recycling burdens shared homocysteine handling.
experimental_model
Bhmt-null mice and wild-type controls.
limitations
Complete knockout, not common human polymorphisms.
nutrient_topic
Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. · Folate (vitamin B9)
organism
Mus musculus
plain_language
Other pathways did not fully compensate.
primary_references
[teng-2011] Deletion of betaine-homocysteine S-methyltransferase in mice perturbs choline and 1-carbon metabolism, resulting in fatty liver and hepatocellular carcinomas (2011). https://pubmed.ncbi.nlm.nih.gov/21878621/ DOI: 10.1074/jbc.m111.265348
tissue_or_cell_type
Liver and plasma
trigger_kind
machinery_impairment Imported condition classification; unverified.
Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 634–644
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Bhmt-null mice and wild-type controls. · source_derived_draft · unverified_draft
### folate-methyl-bhmt-ko-hcy Bhmt deletion raised hepatic total homocysteine sixfold and plasma total homocysteine eightfold in mice. Condition category: machinery_impairment nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Other pathways did not fully compensate. organism: Mus musculus tissue_or_cell_type: Liver and plasma experimental_model: Bhmt-null mice and wild-type controls. limitations: Complete knockout, not common human polymorphisms. cross_nutrient: Loss of betaine recycling burdens shared homocysteine handling. [teng-2011] Deletion of betaine-homocysteine S-methyltransferase in mice perturbs choline and 1-carbon metabolism, resulting in fatty liver and hepatocellular carcinomas (2011). https://pubmed.ncbi.nlm.nih.gov/21878621/ DOI: 10.1074/jbc.m111.265348
Complete structured claim and evidence
Feeding 20 mg folate/kg diet did not ameliorate elevated plasma homocysteine in Bhmt-null mice.
Folic acid → Homocysteine source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
Folate/betaine compensation has limits.
experimental_model
Bhmt-null and wild-type mice; four-week folate feeding.
exposure
0, 2 or 20 mg folate/kg diet
limitations
Mouse four-week experiment, not a human treatment rule.
nutrient_topic
Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. · Folate (vitamin B9)
organism
Mus musculus
plain_language
Extra folate did not restore this missing route.
primary_references
[teng-2012] Homocysteinemia in mice with genetic betaine homocysteine S-methyltransferase deficiency is independent of dietary folate intake (2012). https://pubmed.ncbi.nlm.nih.gov/23014492/ DOI: 10.3945/jn.112.166835
tissue_or_cell_type
Plasma
trigger_kind
machinery_impairment Imported condition classification; unverified.
Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 668–679
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Bhmt-null and wild-type mice; four-week folate feeding. · source_derived_draft · unverified_draft
### folate-methyl-folate-no-hcy-rescue-bhmt Feeding 20 mg folate/kg diet did not ameliorate elevated plasma homocysteine in Bhmt-null mice. Condition category: machinery_impairment nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Extra folate did not restore this missing route. organism: Mus musculus tissue_or_cell_type: Plasma experimental_model: Bhmt-null and wild-type mice; four-week folate feeding. limitations: Mouse four-week experiment, not a human treatment rule. exposure: 0, 2 or 20 mg folate/kg diet cross_nutrient: Folate/betaine compensation has limits. [teng-2012] Homocysteinemia in mice with genetic betaine homocysteine S-methyltransferase deficiency is independent of dietary folate intake (2012). https://pubmed.ncbi.nlm.nih.gov/23014492/ DOI: 10.3945/jn.112.166835
Complete structured claim and evidence
Total homocysteine was elevated in 95.9% of the B12-deficiency episodes; it was also elevated in 91% of the folate-deficiency episodes.
Vitamin B12 (cobalamins) → Homocysteine source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
cross_nutrient
Folate and B12 both participate in homocysteine remethylation.
experimental_model
Selected clear-cut deficiency series: 434 B12 episodes in 406 patients and 123 folate episodes in 119 patients.
exposure
Serum MMA and total homocysteine assays; elevation defined above three standard deviations of the reference mean.
limitations
Circulating concentration is not a direct MTR activity measurement.
nutrient_topic
Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)
organism
Homo sapiens
plain_language
This marker is shared by connected nutrient pathways, so it cannot identify B12 deficiency by itself.
primary_references
[b12-savage1994] Sensitivity of serum methylmalonic acid and total homocysteine determinations for diagnosing cobalamin and folate deficiencies (1994). https://pubmed.ncbi.nlm.nih.gov/8154512/ DOI: 10.1016/0002-9343(94)90149-x
tissue_or_cell_type
Human blood or whole-person endpoints
trigger_kind
biomarker_context Imported condition classification; unverified.
Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1474–1485
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Selected clear-cut deficiency series: 434 B12 episodes in 406 patients and 123 folate episodes in 119 patients. · source_derived_draft · unverified_draft
### b12-deficiency-homocysteine-frequency Total homocysteine was elevated in 95.9% of the B12-deficiency episodes; it was also elevated in 91% of the folate-deficiency episodes. Condition category: biomarker_context nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: This marker is shared by connected nutrient pathways, so it cannot identify B12 deficiency by itself. organism: Homo sapiens tissue_or_cell_type: Human blood or whole-person endpoints experimental_model: Selected clear-cut deficiency series: 434 B12 episodes in 406 patients and 123 folate episodes in 119 patients. limitations: Circulating concentration is not a direct MTR activity measurement. exposure: Serum MMA and total homocysteine assays; elevation defined above three standard deviations of the reference mean. cross_nutrient: Folate and B12 both participate in homocysteine remethylation. [b12-savage1994] Sensitivity of serum methylmalonic acid and total homocysteine determinations for diagnosing cobalamin and folate deficiencies (1994). https://pubmed.ncbi.nlm.nih.gov/8154512/ DOI: 10.1016/0002-9343(94)90149-x
Complete structured claim and evidence

Availability and dependencies

Each situation shows the normal role first, then what the sources report under a specific condition. A shortfall in the diet, a fault in the machinery, and a low blood reading are kept separate because they are not the same thing.

The sources

Every document behind this chapter is preserved word for word. Open one to read it in full with its recorded conflicts marked in place.

Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Fulvic acid: mixture identity, mineral chemistry, signaling and cross-nutrient mechanisms (2026-09-19)AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · unverified_draftRead preserved source
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source

Recorded disagreements

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Evidence, AI assistance and curation standards

Fulvic acid (heterogeneous humic fraction)

The mechanisms

Added homocysteine increased ERK phosphorylation in U937 cells.

Added homocysteine increased JNK phosphorylation in U937 cells.

Fulvic pretreatment reduced homocysteine-stimulated ERK phosphorylation.

Fulvic pretreatment reduced homocysteine-stimulated JNK phosphorylation.

Fulvic pretreatment reduced p65 binding at the COX-2 promoter in stimulated U937 cells.

Fulvic pretreatment reduced homocysteine-induced COX-2 mRNA in primary monocytes and U937 cells.

Fulvic pretreatment reduced PGE2 release after homocysteine stimulation.

Dialysis and centrifugation showed copper association with the tested fulvic mixture.

Fulvic exposure increased intestinal mucosal copper retention at six hours without markedly changing lumen-to-mucosa uptake.

The tested fulvic fraction formed iron(III) complexes within 15 minutes.

Iron(III) reduction to iron(II) occurred over time at pH 2 but was not significant at pH 4.

SS-FA at 0.1-10 micrograms/mL reduced PMA/calcium-ionophore-induced histamine release from KU812 cells.

SS-FA pretreatment altered allergy-associated transcripts in stimulated KU812 cells.

CHD-FA exposure increased membrane permeability in Candida albicans assays.

CHD-FA exposure caused extracellular ATP leakage from Candida cells.

Chitin-synthesis inhibition with nikkomycin Z increased Candida susceptibility to CHD-FA.

The tested fulvic preparation reduced tau filament formation in vitro.

Exposure altered preformed tau fibrils, including shorter filaments.

The specified reagent reduced K18 tau aggregation in RT-QuIC assays.

The reagent reduced tau HTRF aggregation signals, while tau BiFC-positive cell frequency was unchanged.

The reagent reduced alpha-synuclein aggregation signals in co-cultures; proteinase-K resistance was not significantly reduced in transfected-only cells.

Podzol-derived fulvic material increased respiration in isolated rat liver mitochondria.

FulvoFeed at 5 or 50 mg C/L reduced the subsequent copper-associated ROS response.

FulvoFeed at 300 or 500 mg C/L increased the subsequent copper-associated ROS response.

Reference fulvic fractions increased iron import in respiratory epithelial cells.

Reference fulvic fractions increased IL-6 and IL-8 release from respiratory epithelial cells.

Iron co-exposure reduced fulvic-associated IL-6/IL-8 release in the tested cells.

MLG formulations reduced the LPS-induced reporter response.

MLG-A50 increased scratch closure in LoVo-cell assays.

Oral MLG formulations changed measured fecal microbiota composition and diversity in guinea pigs.

The small oral CHD-FA trial reported reduced skin-prick responses.

No severe adverse events were reported and measured safety parameters remained stable during the trial.

Investigator global response favored topical CHD-FA over vehicle; several other measures improved in both groups.

CHD-FA did not produce a clear reproducible mutagenic response in the reported Ames tests.

CHD-FA increased micronucleus frequency in human lymphocyte testing under growth-inhibiting conditions.

CHD-FA did not significantly increase micronucleated polychromatic erythrocytes in tested mice.

Riboflavin lowered plasma homocysteine in the MTHFR 677TT group by 22% overall; the lower-baseline-B2 subgroup showed a 40% decrease.

No homocysteine response was observed in the CC or CT groups despite improved riboflavin-status measures in all genotype groups.

Controlled depletion lowered plasma folate and significantly raised plasma homocysteine in eight postmenopausal women.

Bhmt deletion raised hepatic total homocysteine sixfold and plasma total homocysteine eightfold in mice.

Feeding 20 mg folate/kg diet did not ameliorate elevated plasma homocysteine in Bhmt-null mice.

Total homocysteine was elevated in 95.9% of the B12-deficiency episodes; it was also elevated in 91% of the folate-deficiency episodes.

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Recorded disagreements

Open questions in this collection