Riboflavin (vitamin B2)

evidence_access

Primary full text, results and Figure 6

experimental_model

Randomized placebo-controlled human study; pooled dose analysis.

limitations

Fecal concentration was measured, not production flux. Neither dose increased F. prausnitzii abundance; this does not establish a universal B2 deficiency gate.

nutrient_topic

Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate

plain_language

A vitamin B2 trial found a butyrate signal after pooling doses.

primary_references

Riboflavin Supplementation Promotes Butyrate Production in the Absence of Gross Compositional Changes in the Gut Microbiota. · 2023 · https://pubmed.ncbi.nlm.nih.gov/35943883/ · DOI 10.1089/ars.2022.0033

Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 86–92

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Randomized placebo-controlled human study; pooled dose analysis. · source_derived_draft · unverified_draft

## butyrate-riboflavin-pooled A vitamin B2 trial found a butyrate signal after pooling doses. Combining the 50 and 100 mg/day riboflavin arms in RIBOGUT showed increased fecal butyrate after two weeks; separate-dose analyses showed only minor SCFA differences. Model: Randomized placebo-controlled human study; pooled dose analysis. Limitations: Fecal concentration was measured, not production flux. Neither dose increased F. prausnitzii abundance; this does not establish a universal B2 deficiency gate. Evidence access: Primary full text, results and Figure 6 Riboflavin Supplementation Promotes Butyrate Production in the Absence of Gross Compositional Changes in the Gut Microbiota. · 2023 · https://pubmed.ncbi.nlm.nih.gov/35943883/ · DOI 10.1089/ars.2022.0033

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

Prevents equating altered tryptophan metabolism with universal niacin depletion.

evidence_location

Abstract

experimental_model

Dietary riboflavin-deficient, pyridoxine-deficient, pair-fed and natural-diet baboons; urinary and erythrocyte measurements.

exposure

Experimental riboflavin-deficient diet

limitations

The abstract reports an aggregate red-cell readout; it does not resolve synthesis flux, other tissues or every NAD species.

nutrient_topic

Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)

organism

Papio species (baboon)

plain_language

The B2-related urine change did not establish a fall in this red-cell nucleotide pool.

primary_references

[verjee1975] Tryptophan metabolism in baboons: effect of riboflavin and pyridoxine deficiency. (1975). https://pubmed.ncbi.nlm.nih.gov/23659/

tissue_or_cell_type

Erythrocytes

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1290–1302

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Dietary riboflavin-deficient, pyridoxine-deficient, pair-fed and natural-diet baboons; urinary and erythrocyte measurements. · source_derived_draft · unverified_draft

### b2-baboon-pyridine-nucleotide-boundary Red-cell pyridine nucleotides decreased in pyridoxine-deficient baboons, but not in the riboflavin-deficient group. Condition category: nutrient_deficiency nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The B2-related urine change did not establish a fall in this red-cell nucleotide pool. organism: Papio species (baboon) tissue_or_cell_type: Erythrocytes experimental_model: Dietary riboflavin-deficient, pyridoxine-deficient, pair-fed and natural-diet baboons; urinary and erythrocyte measurements. limitations: The abstract reports an aggregate red-cell readout; it does not resolve synthesis flux, other tissues or every NAD species. exposure: Experimental riboflavin-deficient diet cross_nutrient: Prevents equating altered tryptophan metabolism with universal niacin depletion. evidence_location: Abstract [verjee1975] Tryptophan metabolism in baboons: effect of riboflavin and pyridoxine deficiency. (1975). https://pubmed.ncbi.nlm.nih.gov/23659/

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

Dietary B2 status influences a tryptophan/niacin-pathway readout.

evidence_location

Abstract

experimental_model

Dietary riboflavin-deficient, pyridoxine-deficient, pair-fed and natural-diet baboons; urinary and erythrocyte measurements.

exposure

Experimental riboflavin-deficient diet

limitations

Indexed abstract does not give diet duration or group size; urinary output is not a direct tissue KMO flux measurement.

nutrient_topic

Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)

organism

Papio species (baboon)

plain_language

Dietary B2 deficiency changed a measured tryptophan-pathway product.

primary_references

[verjee1975] Tryptophan metabolism in baboons: effect of riboflavin and pyridoxine deficiency. (1975). https://pubmed.ncbi.nlm.nih.gov/23659/

tissue_or_cell_type

Urine

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1276–1288

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Dietary riboflavin-deficient, pyridoxine-deficient, pair-fed and natural-diet baboons; urinary and erythrocyte measurements. · source_derived_draft · unverified_draft

### b2-baboon-urinary-hydroxykynurenine Riboflavin-deficient baboons excreted approximately one tenth as much urinary 3-hydroxykynurenine in the reported dietary comparison. Condition category: nutrient_deficiency nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Dietary B2 deficiency changed a measured tryptophan-pathway product. organism: Papio species (baboon) tissue_or_cell_type: Urine experimental_model: Dietary riboflavin-deficient, pyridoxine-deficient, pair-fed and natural-diet baboons; urinary and erythrocyte measurements. limitations: Indexed abstract does not give diet duration or group size; urinary output is not a direct tissue KMO flux measurement. exposure: Experimental riboflavin-deficient diet cross_nutrient: Dietary B2 status influences a tryptophan/niacin-pathway readout. evidence_location: Abstract [verjee1975] Tryptophan metabolism in baboons: effect of riboflavin and pyridoxine deficiency. (1975). https://pubmed.ncbi.nlm.nih.gov/23659/

availability_state

biomarker_context Imported condition classification; unverified.

experimental_model

124 healthy older adults, mean age 69; 46 with EGRAC >=1.20 randomized equally to riboflavin or placebo.

exposure

1.6 mg/day riboflavin versus placebo for 12 weeks; HPLC plasma/red-cell vitamer measurements.

limitations

Older adults selected by EGRAC; percentages are study responses, not diagnostic thresholds or predicted individual gains.

nutrient_topic

Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)

organism

Homo sapiens

plain_language

Blood B2 comes in several forms, and they do not all respond equally to intake.

primary_references

[b2-hustad2002] Riboflavin, flavin mononucleotide, and flavin adenine dinucleotide in human plasma and erythrocytes at baseline and after low-dose riboflavin supplementation (2002). https://pubmed.ncbi.nlm.nih.gov/12194936/ DOI: 10.1093/clinchem/48.9.1571

tissue_or_cell_type

Human clinical setting

trigger_kind

biomarker_context Imported condition classification; unverified.

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1617–1627

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 124 healthy older adults, mean age 69; 46 with EGRAC >=1.20 randomized equally to riboflavin or placebo. · source_derived_draft · unverified_draft

### b2-blood-vitamer-response In 46 randomized older adults, supplementation increased plasma riboflavin by 83% and erythrocyte FMN by 87%; measured markers other than plasma FAD responded significantly. Condition category: biomarker_context nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Blood B2 comes in several forms, and they do not all respond equally to intake. organism: Homo sapiens tissue_or_cell_type: Human clinical setting experimental_model: 124 healthy older adults, mean age 69; 46 with EGRAC >=1.20 randomized equally to riboflavin or placebo. limitations: Older adults selected by EGRAC; percentages are study responses, not diagnostic thresholds or predicted individual gains. exposure: 1.6 mg/day riboflavin versus placebo for 12 weeks; HPLC plasma/red-cell vitamer measurements. [b2-hustad2002] Riboflavin, flavin mononucleotide, and flavin adenine dinucleotide in human plasma and erythrocytes at baseline and after low-dose riboflavin supplementation (2002). https://pubmed.ncbi.nlm.nih.gov/12194936/ DOI: 10.1093/clinchem/48.9.1571

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

availability_state

nutrient_deficiency Imported condition classification; unverified.

experimental_model

Erythrocytes from marginally riboflavin-deficient people and controls separated into nine density fractions.

exposure

Red-cell age-fraction enzyme/cofactor assays, glutathione, hemoglobin species and peroxide susceptibility; observational comparison.

limitations

Does not identify a single responsible reductase or prove clinically significant anemia/hemolysis in each person.

nutrient_topic

Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)

organism

Homo sapiens

plain_language

The study found a specific hemoglobin oxidation change, not failure of every antioxidant measure.

primary_references

[b2-powers1981] Riboflavin deficiency in man: effects on haemoglobin and reduced glutathione in erythrocytes of different ages (1981). https://pubmed.ncbi.nlm.nih.gov/7284295/ DOI: 10.1079/bjn19810031

tissue_or_cell_type

Human clinical setting

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1705–1715

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Erythrocytes from marginally riboflavin-deficient people and controls separated into nine density fractions. · source_derived_draft · unverified_draft

### b2-deficiency-methemoglobin Methemoglobin was higher in erythrocytes from the marginally B2-deficient group; the other tested endpoints did not all differ from controls. Condition category: nutrient_deficiency nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The study found a specific hemoglobin oxidation change, not failure of every antioxidant measure. organism: Homo sapiens tissue_or_cell_type: Human clinical setting experimental_model: Erythrocytes from marginally riboflavin-deficient people and controls separated into nine density fractions. limitations: Does not identify a single responsible reductase or prove clinically significant anemia/hemolysis in each person. exposure: Red-cell age-fraction enzyme/cofactor assays, glutathione, hemoglobin species and peroxide susceptibility; observational comparison. [b2-powers1981] Riboflavin deficiency in man: effects on haemoglobin and reduced glutathione in erythrocytes of different ages (1981). https://pubmed.ncbi.nlm.nih.gov/7284295/ DOI: 10.1079/bjn19810031

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

B2 supports a component of glutathione recycling; this is not proof of universal glutathione exhaustion.

experimental_model

Erythrocytes from marginally riboflavin-deficient people and controls separated into nine density fractions.

exposure

Red-cell age-fraction enzyme/cofactor assays, glutathione, hemoglobin species and peroxide susceptibility; observational comparison.

limitations

Observational age-fraction study; reduced glutathione itself was not among the significant between-group differences.

nutrient_topic

Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)

organism

Homo sapiens

plain_language

A B2-dependent recycling enzyme was less active in red cells from the deficient group.

primary_references

[b2-powers1981] Riboflavin deficiency in man: effects on haemoglobin and reduced glutathione in erythrocytes of different ages (1981). https://pubmed.ncbi.nlm.nih.gov/7284295/ DOI: 10.1079/bjn19810031

tissue_or_cell_type

Human clinical setting

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1692–1703

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Erythrocytes from marginally riboflavin-deficient people and controls separated into nine density fractions. · source_derived_draft · unverified_draft

### b2-deficiency-redcell-gsr Marginally B2-deficient subjects had lower erythrocyte glutathione reductase activity than controls across the study comparison. Condition category: nutrient_deficiency nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A B2-dependent recycling enzyme was less active in red cells from the deficient group. organism: Homo sapiens tissue_or_cell_type: Human clinical setting experimental_model: Erythrocytes from marginally riboflavin-deficient people and controls separated into nine density fractions. limitations: Observational age-fraction study; reduced glutathione itself was not among the significant between-group differences. exposure: Red-cell age-fraction enzyme/cofactor assays, glutathione, hemoglobin species and peroxide susceptibility; observational comparison. cross_nutrient: B2 supports a component of glutathione recycling; this is not proof of universal glutathione exhaustion. [b2-powers1981] Riboflavin deficiency in man: effects on haemoglobin and reduced glutathione in erythrocytes of different ages (1981). https://pubmed.ncbi.nlm.nih.gov/7284295/ DOI: 10.1079/bjn19810031

availability_state

biomarker_context Imported condition classification; unverified.

cross_nutrient

B2 cofactor supply affects a B6-activation assay.

experimental_model

Human erythrocytes from G6PD deficiency, heterozygous beta-thalassemia and controls.

exposure

In-vitro FAD stimulation of glutathione reductase and PNP oxidase activity, with oral-riboflavin response observations.

limitations

No isolated whole-body B6 flux or clinical seizure/neuropathy outcome was established.

nutrient_topic

Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)

organism

Homo sapiens

plain_language

FMN and FAD should not be treated as one interchangeable vitamin pool.

primary_references

[b2-anderson1987] Glutathione reductase activity and its relationship to pyridoxine phosphate activity in G6PD deficiency (1987). https://pubmed.ncbi.nlm.nih.gov/3582603/ DOI: 10.1111/j.1600-0609.1987.tb01417.x

tissue_or_cell_type

Human clinical setting

trigger_kind

biomarker_context Imported condition classification; unverified.

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1679–1690

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human erythrocytes from G6PD deficiency, heterozygous beta-thalassemia and controls. · source_derived_draft · unverified_draft

### b2-g6pd-fmn-oxidase-response Low FMN-dependent PNP oxidase activity in many G6PD-deficient participants responded to oral riboflavin despite the contrasting FAD-saturated GSR pattern. Condition category: biomarker_context nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: FMN and FAD should not be treated as one interchangeable vitamin pool. organism: Homo sapiens tissue_or_cell_type: Human clinical setting experimental_model: Human erythrocytes from G6PD deficiency, heterozygous beta-thalassemia and controls. limitations: No isolated whole-body B6 flux or clinical seizure/neuropathy outcome was established. exposure: In-vitro FAD stimulation of glutathione reductase and PNP oxidase activity, with oral-riboflavin response observations. cross_nutrient: B2 cofactor supply affects a B6-activation assay. [b2-anderson1987] Glutathione reductase activity and its relationship to pyridoxine phosphate activity in G6PD deficiency (1987). https://pubmed.ncbi.nlm.nih.gov/3582603/ DOI: 10.1111/j.1600-0609.1987.tb01417.x

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

B2 and iron supply can constrain different parts of erythropoiesis.

experimental_model

Controlled supplementation study in riboflavin-deficient Gambian men with hemoglobin below 11.5 g/dL; stable-isotope iron absorption.

exposure

Oral riboflavin versus no riboflavin; 3.38 mg 58Fe test dose before and after intervention; treatment dose not inferred from accessed abstract.

limitations

Controlled study in anemic deficient men; the specific marrow or mobilization mechanism was inferred, not directly established.

nutrient_topic

Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)

organism

Homo sapiens

plain_language

Hemoglobin improved even though the measured storage marker stayed low.

primary_references

[b2-fairweather1992] Riboflavin deficiency and iron absorption in adult Gambian men (1992). https://pubmed.ncbi.nlm.nih.gov/1590670/ DOI: 10.1159/000177696

tissue_or_cell_type

Human clinical setting

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1578–1589

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Controlled supplementation study in riboflavin-deficient Gambian men with hemoglobin below 11.5 g/dL; stable-isotope iron absorption. · source_derived_draft · unverified_draft

### b2-gambia-hemoglobin Riboflavin supplementation improved B2 status and hemoglobin in deficient Gambian men; low plasma ferritin did not change. Condition category: nutrient_deficiency nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Hemoglobin improved even though the measured storage marker stayed low. organism: Homo sapiens tissue_or_cell_type: Human clinical setting experimental_model: Controlled supplementation study in riboflavin-deficient Gambian men with hemoglobin below 11.5 g/dL; stable-isotope iron absorption. limitations: Controlled study in anemic deficient men; the specific marrow or mobilization mechanism was inferred, not directly established. exposure: Oral riboflavin versus no riboflavin; 3.38 mg 58Fe test dose before and after intervention; treatment dose not inferred from accessed abstract. cross_nutrient: B2 and iron supply can constrain different parts of erythropoiesis. [b2-fairweather1992] Riboflavin deficiency and iron absorption in adult Gambian men (1992). https://pubmed.ncbi.nlm.nih.gov/1590670/ DOI: 10.1159/000177696

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

Iron-use improvement is distinct from intestinal absorption.

experimental_model

Controlled supplementation study in riboflavin-deficient Gambian men with hemoglobin below 11.5 g/dL; stable-isotope iron absorption.

exposure

Oral riboflavin versus no riboflavin; 3.38 mg 58Fe test dose before and after intervention; treatment dose not inferred from accessed abstract.

limitations

Measurement variability and study size limit exclusion of smaller effects; rat intestinal findings need separate model labels.

nutrient_topic

Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)

organism

Homo sapiens

plain_language

This human study does not support a blanket claim that B2 always raises iron absorption.

primary_references

[b2-fairweather1992] Riboflavin deficiency and iron absorption in adult Gambian men (1992). https://pubmed.ncbi.nlm.nih.gov/1590670/ DOI: 10.1159/000177696

tissue_or_cell_type

Human clinical setting

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1591–1602

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Controlled supplementation study in riboflavin-deficient Gambian men with hemoglobin below 11.5 g/dL; stable-isotope iron absorption. · source_derived_draft · unverified_draft

### b2-gambia-iron-absorption Stable-isotope iron absorption varied widely within and between Gambian participants and showed no measurable change after riboflavin. Condition category: nutrient_deficiency nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: This human study does not support a blanket claim that B2 always raises iron absorption. organism: Homo sapiens tissue_or_cell_type: Human clinical setting experimental_model: Controlled supplementation study in riboflavin-deficient Gambian men with hemoglobin below 11.5 g/dL; stable-isotope iron absorption. limitations: Measurement variability and study size limit exclusion of smaller effects; rat intestinal findings need separate model labels. exposure: Oral riboflavin versus no riboflavin; 3.38 mg 58Fe test dose before and after intervention; treatment dose not inferred from accessed abstract. cross_nutrient: Iron-use improvement is distinct from intestinal absorption. [b2-fairweather1992] Riboflavin deficiency and iron absorption in adult Gambian men (1992). https://pubmed.ncbi.nlm.nih.gov/1590670/ DOI: 10.1159/000177696

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

Iron supply alone did not prevent anemia in the combined B2 restriction/antagonist experiment.

experimental_model

Historical induced-depletion study in six men with inoperable cancers; no healthy randomized control group.

exposure

Low-riboflavin semisynthetic diet plus galactoflavin antagonist, followed by riboflavin replacement; three also received oral antibiotics.

limitations

Same six-patient experiment as lesion record; other nutrients were supplied but cancer and antagonist effects limit causal generalization.

nutrient_topic

Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)

organism

Homo sapiens

plain_language

Severe induced shortage reduced new red-cell production; the anemia was not simply assumed to be low dietary iron.

primary_references

[b2-lane1964] THE RAPID INDUCTION OF HUMAN RIBOFLAVIN DEFICIENCY WITH GALACTOFLAVIN (1964). https://pubmed.ncbi.nlm.nih.gov/14135487/ DOI: 10.1172/jci104921

tissue_or_cell_type

Bone marrow and circulating erythrocytes

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1801–1812

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Historical induced-depletion study in six men with inoperable cancers; no healthy randomized control group. · source_derived_draft · unverified_draft

### b2-induced-erythroid-suppression All six patients developed anemia; the study described low reticulocytes and erythroid suppression with recovery during riboflavin replacement. Condition category: nutrient_deficiency nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Severe induced shortage reduced new red-cell production; the anemia was not simply assumed to be low dietary iron. organism: Homo sapiens tissue_or_cell_type: Bone marrow and circulating erythrocytes experimental_model: Historical induced-depletion study in six men with inoperable cancers; no healthy randomized control group. limitations: Same six-patient experiment as lesion record; other nutrients were supplied but cancer and antagonist effects limit causal generalization. exposure: Low-riboflavin semisynthetic diet plus galactoflavin antagonist, followed by riboflavin replacement; three also received oral antibiotics. cross_nutrient: Iron supply alone did not prevent anemia in the combined B2 restriction/antagonist experiment. [b2-lane1964] THE RAPID INDUCTION OF HUMAN RIBOFLAVIN DEFICIENCY WITH GALACTOFLAVIN (1964). https://pubmed.ncbi.nlm.nih.gov/14135487/ DOI: 10.1172/jci104921

availability_state

nutrient_deficiency Imported condition classification; unverified.

experimental_model

Historical induced-depletion study in six men with inoperable cancers; no healthy randomized control group.

exposure

Low-riboflavin semisynthetic diet plus galactoflavin antagonist, followed by riboflavin replacement; three also received oral antibiotics.

limitations

Advanced cancer, antagonist exposure and antibiotic use in three patients; lesions are not diagnostic of B2 deficiency by appearance alone.

nutrient_topic

Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)

organism

Homo sapiens

plain_language

Severely reduced usable B2 affected lips, mouth and skin in this historical experiment.

primary_references

[b2-lane1964] THE RAPID INDUCTION OF HUMAN RIBOFLAVIN DEFICIENCY WITH GALACTOFLAVIN (1964). https://pubmed.ncbi.nlm.nih.gov/14135487/ DOI: 10.1172/jci104921

tissue_or_cell_type

Oral mucosa, lips and skin

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1789–1799

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Historical induced-depletion study in six men with inoperable cancers; no healthy randomized control group. · source_derived_draft · unverified_draft

### b2-induced-mouth-skin-lesions All six patients developed cheilosis and angular stomatitis during combined restriction/galactoflavin exposure; five developed glossitis and all developed dermatitis. Condition category: nutrient_deficiency nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Severely reduced usable B2 affected lips, mouth and skin in this historical experiment. organism: Homo sapiens tissue_or_cell_type: Oral mucosa, lips and skin experimental_model: Historical induced-depletion study in six men with inoperable cancers; no healthy randomized control group. limitations: Advanced cancer, antagonist exposure and antibiotic use in three patients; lesions are not diagnostic of B2 deficiency by appearance alone. exposure: Low-riboflavin semisynthetic diet plus galactoflavin antagonist, followed by riboflavin replacement; three also received oral antibiotics. [b2-lane1964] THE RAPID INDUCTION OF HUMAN RIBOFLAVIN DEFICIENCY WITH GALACTOFLAVIN (1964). https://pubmed.ncbi.nlm.nih.gov/14135487/ DOI: 10.1172/jci104921

availability_state

nutrient_deficiency Imported condition classification; unverified.

experimental_model

Double-blind controlled trial in 60 lactating women from two Gambian villages and their infants.

exposure

Maternal 2 mg/day riboflavin or placebo for 12 weeks; background intake about 0.5 mg/day; supplementation-withdrawal observations.

limitations

Nutritionally constrained population; no direct mammary transporter assay in this trial.

nutrient_topic

Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)

organism

Homo sapiens

plain_language

The mother’s B2 supply affected the vitamin delivered in milk.

primary_references

[b2-bates1982] Riboflavin requirements of lactating Gambian women: a controlled supplementation trial (1982). https://pubmed.ncbi.nlm.nih.gov/7072623/ DOI: 10.1093/ajcn/35.4.701

tissue_or_cell_type

Maternal blood and human milk

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1765–1775

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Double-blind controlled trial in 60 lactating women from two Gambian villages and their infants. · source_derived_draft · unverified_draft

### b2-maternal-milk-response Maternal supplementation increased breast-milk riboflavin and improved maternal status compared with placebo in the Gambian lactation trial. Condition category: nutrient_deficiency nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The mother’s B2 supply affected the vitamin delivered in milk. organism: Homo sapiens tissue_or_cell_type: Maternal blood and human milk experimental_model: Double-blind controlled trial in 60 lactating women from two Gambian villages and their infants. limitations: Nutritionally constrained population; no direct mammary transporter assay in this trial. exposure: Maternal 2 mg/day riboflavin or placebo for 12 weeks; background intake about 0.5 mg/day; supplementation-withdrawal observations. [b2-bates1982] Riboflavin requirements of lactating Gambian women: a controlled supplementation trial (1982). https://pubmed.ncbi.nlm.nih.gov/7072623/ DOI: 10.1093/ajcn/35.4.701

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_spans

[{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC7477094", "locator": "XML .//body//p", "paragraph_index": 21, "char_start": 0, "char_end": 3026, "evidence_access": "full-text"}]

experimental_model

Mouse B16 melanoma cells cultured in riboflavin-free medium for 3 days; quantitative proteomics.

exposure

Three-day riboflavin withdrawal; mass-spectrometry proteomics.

limitations

The response does not demonstrate complete energetic compensation or measured glycolytic flux.

nutrient_topic

Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)

organism

Mus musculus

plain_language

These cells increased glycolytic machinery while their respiratory machinery declined.

primary_references

[martinez-limon-2020-b2-depletion] Flavin dependency undermines proteome stability, lipid metabolism and cellular proliferation during vitamin B2 deficiency (2020). https://pubmed.ncbi.nlm.nih.gov/32895367/ DOI: 10.1038/s41419-020-02929-5

tissue_or_cell_type

B16 melanoma cells

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 983–994

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mouse B16 melanoma cells cultured in riboflavin-free medium for 3 days; quantitative proteomics. · source_derived_draft · unverified_draft

### b2-met-b16-glycolytic-proteome Eight glycolytic enzymes increased in abundance after three days of riboflavin starvation in B16 melanoma cells. Condition category: nutrient_deficiency nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: These cells increased glycolytic machinery while their respiratory machinery declined. organism: Mus musculus tissue_or_cell_type: B16 melanoma cells experimental_model: Mouse B16 melanoma cells cultured in riboflavin-free medium for 3 days; quantitative proteomics. limitations: The response does not demonstrate complete energetic compensation or measured glycolytic flux. exposure: Three-day riboflavin withdrawal; mass-spectrometry proteomics. evidence_spans: [{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC7477094", "locator": "XML .//body//p", "paragraph_index": 21, "char_start": 0, "char_end": 3026, "evidence_access": "full-text"}] [martinez-limon-2020-b2-depletion] Flavin dependency undermines proteome stability, lipid metabolism and cellular proliferation during vitamin B2 deficiency (2020). https://pubmed.ncbi.nlm.nih.gov/32895367/ DOI: 10.1038/s41419-020-02929-5

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_spans

[{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC7477094", "locator": "XML .//body//p", "paragraph_index": 21, "char_start": 0, "char_end": 3026, "evidence_access": "full-text"}]

experimental_model

Mouse B16 melanoma cells cultured in riboflavin-free medium for 3 days; quantitative proteomics.

exposure

Riboflavin-free culture for three days; quantitative proteomics.

limitations

Abundance, not direct pathway flux; cancer-cell dependence may differ from normal cells.

nutrient_topic

Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)

organism

Mus musculus

plain_language

Removing B2 lowered the abundance of respiratory machinery in these tumor cells.

primary_references

[martinez-limon-2020-b2-depletion] Flavin dependency undermines proteome stability, lipid metabolism and cellular proliferation during vitamin B2 deficiency (2020). https://pubmed.ncbi.nlm.nih.gov/32895367/ DOI: 10.1038/s41419-020-02929-5

tissue_or_cell_type

B16 melanoma cells

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 970–981

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mouse B16 melanoma cells cultured in riboflavin-free medium for 3 days; quantitative proteomics. · source_derived_draft · unverified_draft

### b2-met-b16-respiratory-proteome Three-day riboflavin starvation of mouse B16 cells reduced proteomic clusters associated with electron transport and ATP synthesis. Condition category: nutrient_deficiency nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Removing B2 lowered the abundance of respiratory machinery in these tumor cells. organism: Mus musculus tissue_or_cell_type: B16 melanoma cells experimental_model: Mouse B16 melanoma cells cultured in riboflavin-free medium for 3 days; quantitative proteomics. limitations: Abundance, not direct pathway flux; cancer-cell dependence may differ from normal cells. exposure: Riboflavin-free culture for three days; quantitative proteomics. evidence_spans: [{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC7477094", "locator": "XML .//body//p", "paragraph_index": 21, "char_start": 0, "char_end": 3026, "evidence_access": "full-text"}] [martinez-limon-2020-b2-depletion] Flavin dependency undermines proteome stability, lipid metabolism and cellular proliferation during vitamin B2 deficiency (2020). https://pubmed.ncbi.nlm.nih.gov/32895367/ DOI: 10.1038/s41419-020-02929-5

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_spans

[{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC2440658", "locator": "HTML article p", "paragraph_index": 11, "char_start": 0, "char_end": 1107, "evidence_access": "full-text"}]

experimental_model

Bovine heart submitochondrial particles; alkaline reductive inactivation and cofactor reconstitution.

exposure

10 micromolar riboflavin, FAD or FMN in the reconstitution comparison.

limitations

Does not test intact-cell conversion of riboflavin into FMN.

nutrient_topic

Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)

organism

Bos taurus

plain_language

Free B2 and FAD could not substitute directly for FMN in this test tube.

primary_references

[gostimskaya-2007-complex-i-fmn] Reversible dissociation of flavin mononucleotide from the mammalian membrane-bound NADH: ubiquinone oxidoreductase (complex I) (2007). https://pubmed.ncbi.nlm.nih.gov/18037377/ DOI: 10.1016/j.febslet.2007.11.048

tissue_or_cell_type

Heart submitochondrial particles

trigger_kind

machinery_impairment Imported condition classification; unverified.

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 596–607

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Bovine heart submitochondrial particles; alkaline reductive inactivation and cofactor reconstitution. · source_derived_draft · unverified_draft

### b2-met-complex-i-flavin-specificity Riboflavin and FAD failed to protect or reactivate alkaline-inactivated bovine complex I under conditions where FMN did. Condition category: machinery_impairment nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Free B2 and FAD could not substitute directly for FMN in this test tube. organism: Bos taurus tissue_or_cell_type: Heart submitochondrial particles experimental_model: Bovine heart submitochondrial particles; alkaline reductive inactivation and cofactor reconstitution. limitations: Does not test intact-cell conversion of riboflavin into FMN. exposure: 10 micromolar riboflavin, FAD or FMN in the reconstitution comparison. evidence_spans: [{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC2440658", "locator": "HTML article p", "paragraph_index": 11, "char_start": 0, "char_end": 1107, "evidence_access": "full-text"}] [gostimskaya-2007-complex-i-fmn] Reversible dissociation of flavin mononucleotide from the mammalian membrane-bound NADH: ubiquinone oxidoreductase (complex I) (2007). https://pubmed.ncbi.nlm.nih.gov/18037377/ DOI: 10.1016/j.febslet.2007.11.048

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_spans

[{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC10767280", "locator": "XML .//body//p", "paragraph_index": 58, "char_start": 0, "char_end": 905, "evidence_access": "full-text"}]

experimental_model

Human 143B cells and mouse adult fibroblasts, riboflavin-free medium and separate DPI interventions.

exposure

Riboflavin-free medium; matched control contained 1 micromolar riboflavin.

limitations

Cell-culture withdrawal; proteomic abundance does not establish a human blood threshold.

nutrient_topic

Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)

organism

Homo sapiens; Mus musculus

plain_language

Removing B2 reduced parts needed to build the respiratory enzyme.

primary_references

[curtabbi-2024-fmn-assembly] Regulation of respiratory complex I assembly by FMN cofactor targeting (2024). https://pubmed.ncbi.nlm.nih.gov/38145589/ DOI: 10.1016/j.redox.2023.103001

tissue_or_cell_type

143B cells and mouse adult fibroblasts

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 609–620

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human 143B cells and mouse adult fibroblasts, riboflavin-free medium and separate DPI interventions. · source_derived_draft · unverified_draft

### b2-met-depletion-complex-i Riboflavin-free culture reduced complex I abundance; human 143B proteomics identified particularly strong loss of its NADH-oxidizing N-module subunits. Condition category: nutrient_deficiency nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Removing B2 reduced parts needed to build the respiratory enzyme. organism: Homo sapiens; Mus musculus tissue_or_cell_type: 143B cells and mouse adult fibroblasts experimental_model: Human 143B cells and mouse adult fibroblasts, riboflavin-free medium and separate DPI interventions. limitations: Cell-culture withdrawal; proteomic abundance does not establish a human blood threshold. exposure: Riboflavin-free medium; matched control contained 1 micromolar riboflavin. evidence_spans: [{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC10767280", "locator": "XML .//body//p", "paragraph_index": 58, "char_start": 0, "char_end": 905, "evidence_access": "full-text"}] [curtabbi-2024-fmn-assembly] Regulation of respiratory complex I assembly by FMN cofactor targeting (2024). https://pubmed.ncbi.nlm.nih.gov/38145589/ DOI: 10.1016/j.redox.2023.103001

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

Connects B2-dependent DLD abundance to the canonical B1-dependent mitochondrial complexes; this study does not demonstrate failure of thiamine treatment.

evidence_spans

[{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC10767280", "locator": "XML .//body//p", "paragraph_index": 58, "char_start": 0, "char_end": 905, "evidence_access": "full-text"}]

experimental_model

Human 143B cells and mouse adult fibroblasts, riboflavin-free medium and separate DPI interventions.

exposure

Riboflavin-free medium compared with matched replete medium.

limitations

No direct PDH/OGDH flux or thiamine-response experiment; selective loss must not be generalized to all flavoproteins.

nutrient_topic

Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)

organism

Homo sapiens

plain_language

B2 withdrawal destabilized selected flavoproteins, including the shared DLD enzyme.

primary_references

[curtabbi-2024-fmn-assembly] Regulation of respiratory complex I assembly by FMN cofactor targeting (2024). https://pubmed.ncbi.nlm.nih.gov/38145589/ DOI: 10.1016/j.redox.2023.103001

tissue_or_cell_type

143B cell proteomics

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 622–634

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human 143B cells and mouse adult fibroblasts, riboflavin-free medium and separate DPI interventions. · source_derived_draft · unverified_draft

### b2-met-depletion-dld DLD protein abundance decreased in riboflavin-depleted human 143B cells, while many other mitochondrial matrix flavoproteins did not decline. Condition category: nutrient_deficiency nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: B2 withdrawal destabilized selected flavoproteins, including the shared DLD enzyme. organism: Homo sapiens tissue_or_cell_type: 143B cell proteomics experimental_model: Human 143B cells and mouse adult fibroblasts, riboflavin-free medium and separate DPI interventions. limitations: No direct PDH/OGDH flux or thiamine-response experiment; selective loss must not be generalized to all flavoproteins. exposure: Riboflavin-free medium compared with matched replete medium. cross_nutrient: Connects B2-dependent DLD abundance to the canonical B1-dependent mitochondrial complexes; this study does not demonstrate failure of thiamine treatment. evidence_spans: [{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC10767280", "locator": "XML .//body//p", "paragraph_index": 58, "char_start": 0, "char_end": 905, "evidence_access": "full-text"}] [curtabbi-2024-fmn-assembly] Regulation of respiratory complex I assembly by FMN cofactor targeting (2024). https://pubmed.ncbi.nlm.nih.gov/38145589/ DOI: 10.1016/j.redox.2023.103001

experimental_model

Double-blind placebo-controlled trial in 55 migraine patients; intention-to-treat analysis.

exposure

400 mg/day riboflavin or placebo for three months; pharmacological exposure.

limitations

Pharmacological dose, small sample and no direct mitochondrial mechanism measurement; prevention rather than acute pain relief.

nutrient_topic

Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)

organism

Homo sapiens

plain_language

A small adult trial found preventive benefit; it did not establish that migraine is a B2-deficiency disease.

primary_references

[b2-schoenen1998] Effectiveness of high-dose riboflavin in migraine prophylaxis. A randomized controlled trial (1998). https://pubmed.ncbi.nlm.nih.gov/9484373/ DOI: 10.1212/wnl.50.2.466

tissue_or_cell_type

Adults with migraine

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1717–1727

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Double-blind placebo-controlled trial in 55 migraine patients; intention-to-treat analysis. · source_derived_draft · unverified_draft

### b2-migraine-adult-trial A55-person adult migraine trial found lower attack frequency and headache days with riboflavin than placebo. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A small adult trial found preventive benefit; it did not establish that migraine is a B2-deficiency disease. organism: Homo sapiens tissue_or_cell_type: Adults with migraine experimental_model: Double-blind placebo-controlled trial in 55 migraine patients; intention-to-treat analysis. limitations: Pharmacological dose, small sample and no direct mitochondrial mechanism measurement; prevention rather than acute pain relief. exposure: 400 mg/day riboflavin or placebo for three months; pharmacological exposure. [b2-schoenen1998] Effectiveness of high-dose riboflavin in migraine prophylaxis. A randomized controlled trial (1998). https://pubmed.ncbi.nlm.nih.gov/9484373/ DOI: 10.1212/wnl.50.2.466

experimental_model

Randomized double-blind placebo-controlled trial in 48 children with migraine.

exposure

200 mg/day riboflavin versus placebo; primary endpoint>=50% reduction in attack frequency; pharmacological exposure.

limitations

High placebo response and modest sample; null evidence does not prove impossibility of benefit in every child.

nutrient_topic

Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)

organism

Homo sapiens

plain_language

One pediatric trial found no preventive advantage over placebo.

primary_references

[b2-maclennan2008] High-dose riboflavin for migraine prophylaxis in children: a double-blind, randomized, placebo-controlled trial (2008). https://pubmed.ncbi.nlm.nih.gov/18984840/ DOI: 10.1177/0883073808318053

tissue_or_cell_type

Children with migraine

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1729–1739

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized double-blind placebo-controlled trial in 48 children with migraine. · source_derived_draft · unverified_draft

### b2-migraine-child-null In the 48-child trial,>=50% attack reduction occurred in 12/27 riboflavin versus 14/21 placebo participants; no primary or secondary endpoint differed significantly. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: One pediatric trial found no preventive advantage over placebo. organism: Homo sapiens tissue_or_cell_type: Children with migraine experimental_model: Randomized double-blind placebo-controlled trial in 48 children with migraine. limitations: High placebo response and modest sample; null evidence does not prove impossibility of benefit in every child. exposure: 200 mg/day riboflavin versus placebo; primary endpoint>=50% reduction in attack frequency; pharmacological exposure. [b2-maclennan2008] High-dose riboflavin for migraine prophylaxis in children: a double-blind, randomized, placebo-controlled trial (2008). https://pubmed.ncbi.nlm.nih.gov/18984840/ DOI: 10.1177/0883073808318053

experimental_model

90 children ages 5-13 randomized equally to placebo, 100 mg or 200 mg riboflavin; 12-week trial.

exposure

100 or 200 mg/day riboflavin versus placebo; missing follow-up values carried forward from baseline; pharmacological exposure.

limitations

Single-center study, small arms and baseline values carried forward for missing follow-up; genotype and deficiency did not establish the reason for discordance.

nutrient_topic

Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)

organism

Homo sapiens

plain_language

A later pediatric trial reported benefit at the same 200 mg daily exposure used in the earlier negative study.

primary_references

[b2-talebian2018] Prophylactic effect of riboflavin on pediatric migraine: a randomized, double-blind, placebo-controlled trial (2018). https://pubmed.ncbi.nlm.nih.gov/29629048/ DOI: 10.19082/6279

tissue_or_cell_type

Children with migraine

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1741–1751

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 90 children ages 5-13 randomized equally to placebo, 100 mg or 200 mg riboflavin; 12-week trial. · source_derived_draft · unverified_draft

### b2-migraine-child-positive In the 90-child three-arm study,>=50% frequency reduction occurred in 24/30 on 200 mg/day versus 4/30 placebo; 100 mg/day did not show a significant benefit. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A later pediatric trial reported benefit at the same 200 mg daily exposure used in the earlier negative study. organism: Homo sapiens tissue_or_cell_type: Children with migraine experimental_model: 90 children ages 5-13 randomized equally to placebo, 100 mg or 200 mg riboflavin; 12-week trial. limitations: Single-center study, small arms and baseline values carried forward for missing follow-up; genotype and deficiency did not establish the reason for discordance. exposure: 100 or 200 mg/day riboflavin versus placebo; missing follow-up values carried forward from baseline; pharmacological exposure. [b2-talebian2018] Prophylactic effect of riboflavin on pediatric migraine: a randomized, double-blind, placebo-controlled trial (2018). https://pubmed.ncbi.nlm.nih.gov/29629048/ DOI: 10.19082/6279

experimental_model

42 children ages 6-13 in randomized crossover trial; 14 also had tension-type headache.

exposure

50 mg/day riboflavin and placebo for 16 weeks each with four-week washout; pharmacological exposure.

limitations

Different dose from 200 mg trials, overlapping headache phenotypes and small sample; contextual result rather than a direct dose-matched contradiction.

nutrient_topic

Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)

organism

Homo sapiens

plain_language

The type of headache and study exposure matter; a signal for a different headache endpoint is not proof of migraine prevention.

primary_references

[b2-bruijn2010] Medium-dose riboflavin as a prophylactic agent in children with migraine: a preliminary placebo-controlled, randomised, double-blind, cross-over trial (2010). https://pubmed.ncbi.nlm.nih.gov/20974610/ DOI: 10.1177/0333102410365106

tissue_or_cell_type

Children with migraine and some interval tension-type headache

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1753–1763

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 42 children ages 6-13 in randomized crossover trial; 14 also had tension-type headache. · source_derived_draft · unverified_draft

### b2-migraine-lowdose-crossover The 42-child crossover trial found no significant migraine-frequency reduction with 50 mg/day riboflavin; tension-type phenotype headaches showed a separate positive signal. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The type of headache and study exposure matter; a signal for a different headache endpoint is not proof of migraine prevention. organism: Homo sapiens tissue_or_cell_type: Children with migraine and some interval tension-type headache experimental_model: 42 children ages 6-13 in randomized crossover trial; 14 also had tension-type headache. limitations: Different dose from 200 mg trials, overlapping headache phenotypes and small sample; contextual result rather than a direct dose-matched contradiction. exposure: 50 mg/day riboflavin and placebo for 16 weeks each with four-week washout; pharmacological exposure. [b2-bruijn2010] Medium-dose riboflavin as a prophylactic agent in children with migraine: a preliminary placebo-controlled, randomised, double-blind, cross-over trial (2010). https://pubmed.ncbi.nlm.nih.gov/20974610/ DOI: 10.1177/0333102410365106

availability_state

biomarker_context Imported condition classification; unverified.

experimental_model

124 healthy older adults, mean age 69; 46 with EGRAC >=1.20 randomized equally to riboflavin or placebo.

exposure

1.6 mg/day riboflavin versus placebo for 12 weeks; HPLC plasma/red-cell vitamer measurements.

limitations

A result in this population does not invalidate every use of plasma FAD; cellular compartment and clinical state matter.

nutrient_topic

Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)

organism

Homo sapiens

plain_language

A stable plasma FAD reading did not mean that all B2-related pools were unchanged.

primary_references

[b2-hustad2002] Riboflavin, flavin mononucleotide, and flavin adenine dinucleotide in human plasma and erythrocytes at baseline and after low-dose riboflavin supplementation (2002). https://pubmed.ncbi.nlm.nih.gov/12194936/ DOI: 10.1093/clinchem/48.9.1571

tissue_or_cell_type

Human clinical setting

trigger_kind

biomarker_context Imported condition classification; unverified.

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1629–1639

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 124 healthy older adults, mean age 69; 46 with EGRAC >=1.20 randomized equally to riboflavin or placebo. · source_derived_draft · unverified_draft

### b2-plasma-fad-nonresponse Plasma FAD did not respond significantly to supplementation in the older-adult trial although plasma riboflavin, erythrocyte FMN and other measures did. Condition category: biomarker_context nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A stable plasma FAD reading did not mean that all B2-related pools were unchanged. organism: Homo sapiens tissue_or_cell_type: Human clinical setting experimental_model: 124 healthy older adults, mean age 69; 46 with EGRAC >=1.20 randomized equally to riboflavin or placebo. limitations: A result in this population does not invalidate every use of plasma FAD; cellular compartment and clinical state matter. exposure: 1.6 mg/day riboflavin versus placebo for 12 weeks; HPLC plasma/red-cell vitamer measurements. [b2-hustad2002] Riboflavin, flavin mononucleotide, and flavin adenine dinucleotide in human plasma and erythrocytes at baseline and after low-dose riboflavin supplementation (2002). https://pubmed.ncbi.nlm.nih.gov/12194936/ DOI: 10.1093/clinchem/48.9.1571

availability_state

biomarker_context Imported condition classification; unverified.

cross_nutrient

A B6-activation enzyme provides a B2-sensitive functional assay.

experimental_model

Assay-development study using hemolysates from the RIBOFEM riboflavin intervention; same trial registration ISRCTN35811298.

exposure

Erythrocyte PPO activity with/without flavin activation; 2 and 4 mg/day supplementation arms. Not independent replication of RIBOFEM.

limitations

Assay-development analysis shares samples with RIBOFEM; not independent replication. Proposed utility in G6PD deficiency requires population-specific validation.

nutrient_topic

Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)

organism

Homo sapiens

plain_language

An enzyme used to activate B6 can also reveal aspects of B2 status because it needs an FMN cofactor.

primary_references

[b2-mushtaq2009] Erythrocyte pyridoxamine phosphate oxidase activity: a potential biomarker of riboflavin status? (2009). https://pubmed.ncbi.nlm.nih.gov/19740970/ DOI: 10.3945/ajcn.2009.28338

tissue_or_cell_type

Human clinical setting

trigger_kind

biomarker_context Imported condition classification; unverified.

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1653–1664

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Assay-development study using hemolysates from the RIBOFEM riboflavin intervention; same trial registration ISRCTN35811298. · source_derived_draft · unverified_draft

### b2-ppo-biomarker-response Erythrocyte PPO activity and its activation coefficient responded to B2 supplementation and correlated with EGRAC; enzyme activity showed a dose response. Condition category: biomarker_context nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: An enzyme used to activate B6 can also reveal aspects of B2 status because it needs an FMN cofactor. organism: Homo sapiens tissue_or_cell_type: Human clinical setting experimental_model: Assay-development study using hemolysates from the RIBOFEM riboflavin intervention; same trial registration ISRCTN35811298. limitations: Assay-development analysis shares samples with RIBOFEM; not independent replication. Proposed utility in G6PD deficiency requires population-specific validation. exposure: Erythrocyte PPO activity with/without flavin activation; 2 and 4 mg/day supplementation arms. Not independent replication of RIBOFEM. cross_nutrient: A B6-activation enzyme provides a B2-sensitive functional assay. [b2-mushtaq2009] Erythrocyte pyridoxamine phosphate oxidase activity: a potential biomarker of riboflavin status? (2009). https://pubmed.ncbi.nlm.nih.gov/19740970/ DOI: 10.3945/ajcn.2009.28338

cross_nutrient

Direct clinical comparison involving B2, vitamin A, iron and folic acid.

experimental_model

366 anemic pregnant women in rural China randomized among four groups for two months; all received iron and folic acid.

exposure

All arms: 60 mg/day iron plus 400 micrograms/day folic acid; added retinol 2000 micrograms/day, riboflavin 1 mg/day, both, or neither. Trial exposures, not recommendations.

limitations

Combination effect cannot be assigned solely to B2 or assumed to be biochemical synergy; anemic pregnant population, multiple co-deficiencies, two-month endpoint.

nutrient_topic

Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)

organism

Homo sapiens

plain_language

Several nutrients were limiting in this population; the combination helped more than iron and folic acid alone.

primary_references

[b2-ma2008] Retinol and riboflavin supplementation decreases the prevalence of anemia in Chinese pregnant women taking iron and folic Acid supplements (2008). https://pubmed.ncbi.nlm.nih.gov/18806105/ DOI: 10.1093/jn/138.10.1946

tissue_or_cell_type

Human clinical setting

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1604–1615

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 366 anemic pregnant women in rural China randomized among four groups for two months; all received iron and folic acid. · source_derived_draft · unverified_draft

### b2-pregnancy-multiple-nutrients Adding retinol and/or riboflavin to iron-folic-acid treatment reduced anemia prevalence more than iron-folic-acid alone; the combined retinol-riboflavin arm gained 5.4±1.1 g/L more hemoglobin than the reference arm. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Several nutrients were limiting in this population; the combination helped more than iron and folic acid alone. organism: Homo sapiens tissue_or_cell_type: Human clinical setting experimental_model: 366 anemic pregnant women in rural China randomized among four groups for two months; all received iron and folic acid. limitations: Combination effect cannot be assigned solely to B2 or assumed to be biochemical synergy; anemic pregnant population, multiple co-deficiencies, two-month endpoint. exposure: All arms: 60 mg/day iron plus 400 micrograms/day folic acid; added retinol 2000 micrograms/day, riboflavin 1 mg/day, both, or neither. Trial exposures, not recommendations. cross_nutrient: Direct clinical comparison involving B2, vitamin A, iron and folic acid. [b2-ma2008] Retinol and riboflavin supplementation decreases the prevalence of anemia in Chinese pregnant women taking iron and folic Acid supplements (2008). https://pubmed.ncbi.nlm.nih.gov/18806105/ DOI: 10.1093/jn/138.10.1946

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

Altered B2-dependent intestinal maintenance may affect endogenous iron retention.

evidence_location

Abstract

experimental_model

Riboflavin-deficient weanling rats; weight-matched and ad-libitum controls; intestinal histology and intraperitoneal 59Fe tracing.

exposure

Dietary riboflavin deficiency

limitations

Association with iron loss does not prove that epithelial turnover alone caused it.

nutrient_topic

Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)

organism

Rattus norvegicus

plain_language

The intestinal lining was renewed faster during deficiency.

primary_references

[powers1993] A proposed intestinal mechanism for the effect of riboflavin deficiency on iron loss in the rat. (1993). https://pubmed.ncbi.nlm.nih.gov/8490008/ DOI: 10.1079/bjn19930055

tissue_or_cell_type

Upper and middle small intestine

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1444–1456

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Riboflavin-deficient weanling rats; weight-matched and ad-libitum controls; intestinal histology and intraperitoneal 59Fe tracing. · source_derived_draft · unverified_draft

### b2-rat-crypt-production Riboflavin-deficient weanling rats showed approximately doubled crypt-cell production and deeper small-intestinal crypts versus controls. Condition category: nutrient_deficiency nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The intestinal lining was renewed faster during deficiency. organism: Rattus norvegicus tissue_or_cell_type: Upper and middle small intestine experimental_model: Riboflavin-deficient weanling rats; weight-matched and ad-libitum controls; intestinal histology and intraperitoneal 59Fe tracing. limitations: Association with iron loss does not prove that epithelial turnover alone caused it. exposure: Dietary riboflavin deficiency cross_nutrient: Altered B2-dependent intestinal maintenance may affect endogenous iron retention. evidence_location: Abstract [powers1993] A proposed intestinal mechanism for the effect of riboflavin deficiency on iron loss in the rat. (1993). https://pubmed.ncbi.nlm.nih.gov/8490008/ DOI: 10.1079/bjn19930055

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

B2 status affected post-absorption iron retention in rats.

evidence_location

Abstract

experimental_model

Riboflavin-deficient weanling rats; weight-matched and ad-libitum controls; intestinal histology and intraperitoneal 59Fe tracing.

exposure

Dietary riboflavin deficiency plus intraperitoneal tracer

limitations

The proposed enterocyte-turnover mechanism is supported indirectly; this is not measurement of unabsorbed oral iron.

nutrient_topic

Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)

organism

Rattus norvegicus

plain_language

Deficiency increased loss of iron already inside the body.

primary_references

[powers1993] A proposed intestinal mechanism for the effect of riboflavin deficiency on iron loss in the rat. (1993). https://pubmed.ncbi.nlm.nih.gov/8490008/ DOI: 10.1079/bjn19930055

tissue_or_cell_type

Gastrointestinal tract and feces

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1458–1470

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Riboflavin-deficient weanling rats; weight-matched and ad-libitum controls; intestinal histology and intraperitoneal 59Fe tracing. · source_derived_draft · unverified_draft

### b2-rat-endogenous-iron-loss After intraperitoneal 59Fe, riboflavin-deficient rats lost about twice as much endogenous tracer in feces as weight-matched controls. Condition category: nutrient_deficiency nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Deficiency increased loss of iron already inside the body. organism: Rattus norvegicus tissue_or_cell_type: Gastrointestinal tract and feces experimental_model: Riboflavin-deficient weanling rats; weight-matched and ad-libitum controls; intestinal histology and intraperitoneal 59Fe tracing. limitations: The proposed enterocyte-turnover mechanism is supported indirectly; this is not measurement of unabsorbed oral iron. exposure: Dietary riboflavin deficiency plus intraperitoneal tracer cross_nutrient: B2 status affected post-absorption iron retention in rats. evidence_location: Abstract [powers1993] A proposed intestinal mechanism for the effect of riboflavin deficiency on iron loss in the rat. (1993). https://pubmed.ncbi.nlm.nih.gov/8490008/ DOI: 10.1079/bjn19930055

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

B2 status changed systemic appearance of administered iron.

evidence_location

Abstract

experimental_model

Dietary riboflavin-deficient male rats versus age-/weight-matched controls; intragastric 59Fe and mucosal brush-border vesicles.

exposure

Dietary riboflavin deficiency plus intragastric 59Fe

limitations

Rat tracer experiment; does not establish an identical human absorption response.

nutrient_topic

Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)

organism

Rattus norvegicus

plain_language

Less of the administered iron reached the blood.

primary_references

[butler1993] Comparison of changes in the uptake and mucosal processing of iron in riboflavin-deficient rats. (1993). https://pubmed.ncbi.nlm.nih.gov/8358336/

tissue_or_cell_type

Intestine and plasma

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1416–1428

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Dietary riboflavin-deficient male rats versus age-/weight-matched controls; intragastric 59Fe and mucosal brush-border vesicles. · source_derived_draft · unverified_draft

### b2-rat-enteral-iron-transfer Riboflavin-deficient rats transferred less intragastrically administered 59Fe to plasma than age- or weight-matched controls. Condition category: nutrient_deficiency nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Less of the administered iron reached the blood. organism: Rattus norvegicus tissue_or_cell_type: Intestine and plasma experimental_model: Dietary riboflavin-deficient male rats versus age-/weight-matched controls; intragastric 59Fe and mucosal brush-border vesicles. limitations: Rat tracer experiment; does not establish an identical human absorption response. exposure: Dietary riboflavin deficiency plus intragastric 59Fe cross_nutrient: B2 status changed systemic appearance of administered iron. evidence_location: Abstract [butler1993] Comparison of changes in the uptake and mucosal processing of iron in riboflavin-deficient rats. (1993). https://pubmed.ncbi.nlm.nih.gov/8358336/

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

B2 deficiency impairs an iron-uptake process in this rat model.

evidence_location

Abstract

experimental_model

Dietary riboflavin-deficient male rats versus age-/weight-matched controls; intragastric 59Fe and mucosal brush-border vesicles.

exposure

Dietary riboflavin deficiency

limitations

No specific transporter or ferrireductase was identified; the result must not be assigned to DMT1, DCYTB or ferritin release without evidence.

nutrient_topic

Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)

organism

Rattus norvegicus

plain_language

The deficiency affected iron entry at the intestinal surface.

primary_references

[butler1993] Comparison of changes in the uptake and mucosal processing of iron in riboflavin-deficient rats. (1993). https://pubmed.ncbi.nlm.nih.gov/8358336/

tissue_or_cell_type

Intestinal brush-border membrane vesicles

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1402–1414

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Dietary riboflavin-deficient male rats versus age-/weight-matched controls; intragastric 59Fe and mucosal brush-border vesicles. · source_derived_draft · unverified_draft

### b2-rat-iron-brush-border-uptake Brush-border membrane vesicles from riboflavin-deficient rats took up less iron than identically prepared control vesicles. Condition category: nutrient_deficiency nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The deficiency affected iron entry at the intestinal surface. organism: Rattus norvegicus tissue_or_cell_type: Intestinal brush-border membrane vesicles experimental_model: Dietary riboflavin-deficient male rats versus age-/weight-matched controls; intragastric 59Fe and mucosal brush-border vesicles. limitations: No specific transporter or ferrireductase was identified; the result must not be assigned to DMT1, DCYTB or ferritin release without evidence. exposure: Dietary riboflavin deficiency cross_nutrient: B2 deficiency impairs an iron-uptake process in this rat model. evidence_location: Abstract [butler1993] Comparison of changes in the uptake and mucosal processing of iron in riboflavin-deficient rats. (1993). https://pubmed.ncbi.nlm.nih.gov/8358336/

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

Constrains the proposed B2-iron mechanism.

evidence_location

Abstract

experimental_model

Dietary riboflavin-deficient male rats versus age-/weight-matched controls; intragastric 59Fe and mucosal brush-border vesicles.

exposure

Dietary riboflavin deficiency; 30-minute tracer endpoint

limitations

Only the reported pools and time point were compared.

nutrient_topic

Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)

organism

Rattus norvegicus

plain_language

The uptake decrease was not explained by the tested redistribution hypothesis.

primary_references

[butler1993] Comparison of changes in the uptake and mucosal processing of iron in riboflavin-deficient rats. (1993). https://pubmed.ncbi.nlm.nih.gov/8358336/

tissue_or_cell_type

Intestinal mucosa

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1430–1442

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Dietary riboflavin-deficient male rats versus age-/weight-matched controls; intragastric 59Fe and mucosal brush-border vesicles. · source_derived_draft · unverified_draft

### b2-rat-iron-partition-preserved Thirty minutes after iron dosing, riboflavin-deficient rats had less mucosal 59Fe but unchanged relative partition between ferritin and transferrin. Condition category: nutrient_deficiency nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The uptake decrease was not explained by the tested redistribution hypothesis. organism: Rattus norvegicus tissue_or_cell_type: Intestinal mucosa experimental_model: Dietary riboflavin-deficient male rats versus age-/weight-matched controls; intragastric 59Fe and mucosal brush-border vesicles. limitations: Only the reported pools and time point were compared. exposure: Dietary riboflavin deficiency; 30-minute tracer endpoint cross_nutrient: Constrains the proposed B2-iron mechanism. evidence_location: Abstract [butler1993] Comparison of changes in the uptake and mucosal processing of iron in riboflavin-deficient rats. (1993). https://pubmed.ncbi.nlm.nih.gov/8358336/

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

Iron absorption and iron use remain separate entities.

experimental_model

RIBOFEM: 123 UK women aged 19-25 randomized with EGRAC >1.40; 119 completed, 117 analyzed after two exclusions; iron-absorption subset 34.

exposure

Placebo, 2 or 4 mg/day riboflavin for eight weeks; historical trial regimens.

limitations

Small absorption subgroup; no measured change is not proof of identical absorption in all settings. Actual downstream causal step remains unresolved.

nutrient_topic

Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)

organism

Homo sapiens

plain_language

The blood response could not simply be explained by absorbing more iron in the measured subgroup.

primary_references

[b2-powers2011] Correcting a marginal riboflavin deficiency improves hematologic status in young women in the United Kingdom (RIBOFEM) (2011). https://pubmed.ncbi.nlm.nih.gov/21525198/ DOI: 10.3945/ajcn.110.008409

tissue_or_cell_type

Human clinical setting

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1565–1576

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · RIBOFEM: 123 UK women aged 19-25 randomized with EGRAC >1.40; 119 completed, 117 analyzed after two exclusions; iron-absorption subset 34. · source_derived_draft · unverified_draft

### b2-ribofem-absorption RIBOFEM found no change in dietary iron intake or measured iron absorption during the riboflavin intervention. Condition category: nutrient_deficiency nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The blood response could not simply be explained by absorbing more iron in the measured subgroup. organism: Homo sapiens tissue_or_cell_type: Human clinical setting experimental_model: RIBOFEM: 123 UK women aged 19-25 randomized with EGRAC >1.40; 119 completed, 117 analyzed after two exclusions; iron-absorption subset 34. limitations: Small absorption subgroup; no measured change is not proof of identical absorption in all settings. Actual downstream causal step remains unresolved. exposure: Placebo, 2 or 4 mg/day riboflavin for eight weeks; historical trial regimens. cross_nutrient: Iron absorption and iron use remain separate entities. [b2-powers2011] Correcting a marginal riboflavin deficiency improves hematologic status in young women in the United Kingdom (RIBOFEM) (2011). https://pubmed.ncbi.nlm.nih.gov/21525198/ DOI: 10.3945/ajcn.110.008409

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

Riboflavin status modifies iron-related hematologic outcomes.

experimental_model

RIBOFEM: 123 UK women aged 19-25 randomized with EGRAC >1.40; 119 completed, 117 analyzed after two exclusions; iron-absorption subset 34.

exposure

Placebo, 2 or 4 mg/day riboflavin for eight weeks; historical trial regimens.

limitations

Baseline-tertile and response associations should not be restated as a uniform hemoglobin benefit in every randomized participant.

nutrient_topic

Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)

organism

Homo sapiens

plain_language

Women with poorer starting B2 status tended to gain more hemoglobin when their B2 status improved.

primary_references

[b2-powers2011] Correcting a marginal riboflavin deficiency improves hematologic status in young women in the United Kingdom (RIBOFEM) (2011). https://pubmed.ncbi.nlm.nih.gov/21525198/ DOI: 10.3945/ajcn.110.008409

tissue_or_cell_type

Human clinical setting

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1552–1563

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · RIBOFEM: 123 UK women aged 19-25 randomized with EGRAC >1.40; 119 completed, 117 analyzed after two exclusions; iron-absorption subset 34. · source_derived_draft · unverified_draft

### b2-ribofem-hemoglobin In RIBOFEM, improvement in B2 status correlated with hemoglobin increase among supplemented women; women with baseline EGRAC >1.65 had the greater hemoglobin response. Condition category: nutrient_deficiency nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Women with poorer starting B2 status tended to gain more hemoglobin when their B2 status improved. organism: Homo sapiens tissue_or_cell_type: Human clinical setting experimental_model: RIBOFEM: 123 UK women aged 19-25 randomized with EGRAC >1.40; 119 completed, 117 analyzed after two exclusions; iron-absorption subset 34. limitations: Baseline-tertile and response associations should not be restated as a uniform hemoglobin benefit in every randomized participant. exposure: Placebo, 2 or 4 mg/day riboflavin for eight weeks; historical trial regimens. cross_nutrient: Riboflavin status modifies iron-related hematologic outcomes. [b2-powers2011] Correcting a marginal riboflavin deficiency improves hematologic status in young women in the United Kingdom (RIBOFEM) (2011). https://pubmed.ncbi.nlm.nih.gov/21525198/ DOI: 10.3945/ajcn.110.008409

availability_state

machinery_impairment Imported condition classification; unverified.

experimental_model

Four-year follow-up of 83 prior participants; 31 TT participants underwent repeat intervention with former treatment assignments reversed.

exposure

1.6 mg/day for 16 weeks in 2004 and again in 2008 with reversed allocations; not four years of continuous supplementation.

limitations

Follow-up selection, small TT sample and changing antihypertensive treatment limit inference; overlaps earlier cohort.

nutrient_topic

Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)

organism

Homo sapiens

plain_language

The earlier participants were studied again; this supports repeat responsiveness but is not an independent population or continuous four-year treatment.

primary_references

[b2-wilson2012] Riboflavin offers a targeted strategy for managing hypertension in patients with the MTHFR 677TT genotype: a 4-y follow-up (2012). https://pubmed.ncbi.nlm.nih.gov/22277556/ DOI: 10.3945/ajcn.111.026245

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 1540–1550

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Four-year follow-up of 83 prior participants; 31 TT participants underwent repeat intervention with former treatment assignments reversed. · source_derived_draft · unverified_draft

### b2-tt-bp-rechallenge A four-year follow-up with reversed intervention assignments in 31 TT participants again reported BP lowering during riboflavin administration. Condition category: machinery_impairment nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The earlier participants were studied again; this supports repeat responsiveness but is not an independent population or continuous four-year treatment. organism: Homo sapiens tissue_or_cell_type: Human clinical setting experimental_model: Four-year follow-up of 83 prior participants; 31 TT participants underwent repeat intervention with former treatment assignments reversed. limitations: Follow-up selection, small TT sample and changing antihypertensive treatment limit inference; overlaps earlier cohort. exposure: 1.6 mg/day for 16 weeks in 2004 and again in 2008 with reversed allocations; not four years of continuous supplementation. [b2-wilson2012] Riboflavin offers a targeted strategy for managing hypertension in patients with the MTHFR 677TT genotype: a 4-y follow-up (2012). https://pubmed.ncbi.nlm.nih.gov/22277556/ DOI: 10.3945/ajcn.111.026245

availability_state

machinery_impairment Imported condition classification; unverified.

cross_nutrient

Gene-cofactor clinical interaction; mechanism mediation was not demonstrated.

experimental_model

91 hypertensive adults with MTHFR 677TT and no overt cardiovascular disease; randomized trial on usual antihypertensive treatment.

exposure

1.6 mg/day riboflavin versus placebo for 16 weeks; experimental regimen.

limitations

Selected TT population; no proof of universal BP benefit, event reduction or a specific NO/methylation mechanism. Null diastolic endpoint retained.

nutrient_topic

Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)

organism

Homo sapiens

plain_language

A genotype-targeted trial found a systolic blood-pressure benefit while participants continued their usual medicines.

primary_references

[b2-wilson2013] Blood pressure in treated hypertensive individuals with the MTHFR 677TT genotype is responsive to intervention with riboflavin: findings of a targeted randomized trial (2013). https://pubmed.ncbi.nlm.nih.gov/23608654/ DOI: 10.1161/hypertensionaha.111.01047

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 1527–1538

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 91 hypertensive adults with MTHFR 677TT and no overt cardiovascular disease; randomized trial on usual antihypertensive treatment. · source_derived_draft · unverified_draft

### b2-tt-bp-trial In hypertensive adults with MTHFR 677TT, the systolic treatment effect was 5.6±2.6 mmHg favoring riboflavin; the diastolic effect was not significant. Condition category: machinery_impairment nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A genotype-targeted trial found a systolic blood-pressure benefit while participants continued their usual medicines. organism: Homo sapiens tissue_or_cell_type: Human clinical setting experimental_model: 91 hypertensive adults with MTHFR 677TT and no overt cardiovascular disease; randomized trial on usual antihypertensive treatment. limitations: Selected TT population; no proof of universal BP benefit, event reduction or a specific NO/methylation mechanism. Null diastolic endpoint retained. exposure: 1.6 mg/day riboflavin versus placebo for 16 weeks; experimental regimen. cross_nutrient: Gene-cofactor clinical interaction; mechanism mediation was not demonstrated. [b2-wilson2013] Blood pressure in treated hypertensive individuals with the MTHFR 677TT genotype is responsive to intervention with riboflavin: findings of a targeted randomized trial (2013). https://pubmed.ncbi.nlm.nih.gov/23608654/ DOI: 10.1161/hypertensionaha.111.01047

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

availability_state

machinery_impairment Imported condition classification; unverified.

cross_nutrient

B2/MTHFR connects folate-dependent remethylation with methionine-cycle biomarkers.

experimental_model

Archived samples from prior BP trials: 115 genotype-characterized adults; TT intervention subset 24 riboflavin and 23 placebo.

exposure

1.6 mg/day riboflavin or placebo for 16 weeks; LC-MS/MS plasma metabolites; secondary analysis, not a new independent trial.

limitations

Secondary sample analysis of prior BP trials; plasma SAM is not tissue SAM flux, DNA methylation, epigenetic silencing or a proved mediator of BP.

nutrient_topic

Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)

organism

Homo sapiens

plain_language

B2 changed selected circulating methylation-related metabolites; the study did not show that every tissue had been short of methyl groups.

primary_references

[b2-robinson2020] Impact of the MTHFR C677T polymorphism on one-carbon metabolites: Evidence from a randomised trial of riboflavin supplementation (2020). https://pubmed.ncbi.nlm.nih.gov/32330571/ DOI: 10.1016/j.biochi.2020.04.004

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 1514–1525

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Archived samples from prior BP trials: 115 genotype-characterized adults; TT intervention subset 24 riboflavin and 23 placebo. · source_derived_draft · unverified_draft

### b2-tt-plasma-sam-response In the 47-person TT intervention subset, riboflavin increased plasma SAM and cystathionine; no response was detected in the other measured one-carbon metabolites. Condition category: machinery_impairment nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: B2 changed selected circulating methylation-related metabolites; the study did not show that every tissue had been short of methyl groups. organism: Homo sapiens tissue_or_cell_type: Human clinical setting experimental_model: Archived samples from prior BP trials: 115 genotype-characterized adults; TT intervention subset 24 riboflavin and 23 placebo. limitations: Secondary sample analysis of prior BP trials; plasma SAM is not tissue SAM flux, DNA methylation, epigenetic silencing or a proved mediator of BP. exposure: 1.6 mg/day riboflavin or placebo for 16 weeks; LC-MS/MS plasma metabolites; secondary analysis, not a new independent trial. cross_nutrient: B2/MTHFR connects folate-dependent remethylation with methionine-cycle biomarkers. [b2-robinson2020] Impact of the MTHFR C677T polymorphism on one-carbon metabolites: Evidence from a randomised trial of riboflavin supplementation (2020). https://pubmed.ncbi.nlm.nih.gov/32330571/ DOI: 10.1016/j.biochi.2020.04.004

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_location

Effect of RF supplementation on animal phenotype

experimental_model

Riboflavin supplementation in conditional-knockout mice

exposure

Pharmacological riboflavin supplementation as described by the study.

limitations

The rescue does not establish the residual entry route or an effective human dose.

nutrient_topic

Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)

organism

Mus musculus

plain_language

Higher riboflavin exposure rescued growth in this transporter-loss mouse model.

primary_references

[transport-intestinal-ko-2016] Conditional (intestinal-specific) knockout of the riboflavin transporter-3 (RFVT-3) impairs riboflavin absorption. (2016). https://pubmed.ncbi.nlm.nih.gov/26660539/ DOI: 10.1152/ajpgi.00340.2015

tissue_or_cell_type

Whole-animal postnatal growth

trigger_kind

machinery_impairment Imported condition classification; unverified.

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 280–291

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Riboflavin supplementation in conditional-knockout mice · source_derived_draft · unverified_draft

### transport-intestinal-ko-growth-rescue Pharmacological riboflavin supplementation corrected growth retardation in the intestinal Slc52a3 conditional-knockout mice. Condition category: machinery_impairment nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Higher riboflavin exposure rescued growth in this transporter-loss mouse model. organism: Mus musculus tissue_or_cell_type: Whole-animal postnatal growth experimental_model: Riboflavin supplementation in conditional-knockout mice limitations: The rescue does not establish the residual entry route or an effective human dose. exposure: Pharmacological riboflavin supplementation as described by the study. evidence_location: Effect of RF supplementation on animal phenotype [transport-intestinal-ko-2016] Conditional (intestinal-specific) knockout of the riboflavin transporter-3 (RFVT-3) impairs riboflavin absorption. (2016). https://pubmed.ncbi.nlm.nih.gov/26660539/ DOI: 10.1152/ajpgi.00340.2015

evidence_span

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experimental_model

High-dose rat toxicity experiments with supporting cell assays

exposure

High boric-acid exposure; testis boron approximately 1–2 mM

limitations

High-exposure animal toxicity does not specify a human dietary threshold. The indexed abstract is truncated; no unreported plasminogen-activator or cAMP result is inferred.

nutrient_topic

Boron research collection; topical membership is not evidence of a direct dietary effect. · Boron

organism

Rat

plain_language

The researchers tested the B2-depletion explanation and did not find support for it.

primary_references

[boron-p7889890] Mechanism of the testicular toxicity of boric acid in rats: in vivo and in vitro studies. (1994). https://pubmed.ncbi.nlm.nih.gov/7889890/ DOI: 10.1289/ehp.94102s799

tissue_or_cell_type

Testis, brain, tissue flavins and isolated Leydig cells

Boron: chemistry, nutrient interactions, low-intake studies and mechanistic uncertainties (2026-09-17) · lines 1158–1169

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · High-dose rat toxicity experiments with supporting cell assays · source_derived_draft · unverified_draft

### boron-rat-toxicity-not-b2-depletion The rat toxicity study found neither tissue-flavin changes nor overt riboflavin-deficiency signs supporting B2 depletion as the cause of boric-acid testicular toxicity. Condition category: normal nutrient_topic: Boron research collection; topical membership is not evidence of a direct dietary effect. plain_language: The researchers tested the B2-depletion explanation and did not find support for it. organism: Rat tissue_or_cell_type: Testis, brain, tissue flavins and isolated Leydig cells experimental_model: High-dose rat toxicity experiments with supporting cell assays limitations: High-exposure animal toxicity does not specify a human dietary threshold. The indexed abstract is truncated; no unreported plasminogen-activator or cAMP result is inferred. exposure: High boric-acid exposure; testis boron approximately 1–2 mM evidence_span: {"source_cache": "artifacts/boron-research/7889890.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "73e5c915a0c7a8fa107ff62480430e94c1cf5c40648f37e08d0266394b05b70a", "start_char": 0, "end_char": 1729, "text_sha256": "73e5c915a0c7a8fa107ff62480430e94c1cf5c40648f37e08d0266394b05b70a"} [boron-p7889890] Mechanism of the testicular toxicity of boric acid in rats: in vivo and in vitro studies. (1994). https://pubmed.ncbi.nlm.nih.gov/7889890/ DOI: 10.1289/ehp.94102s799

evidence_span

{"source_cache": "artifacts/boron-research/42012780.fulltext.txt", "locator": "Exact primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "673f9c1649ebaea729fb8331f6394dcad15d21b7bea8e6414542210b8e9fdd69", "start_char": 6857, "end_char": 8798, "text_sha256": "09a30283b0d51a099a2687875db729353a5f03f83f616c974d75a284679f1f8f"}

experimental_model

Negative-ion electrospray mass spectrometry

exposure

200 µM riboflavin and 400 µM boric acid in WAT solvent at pH 10.3

limitations

Nominal mass is consistent with, but does not uniquely establish, the proposed 1:1 structure. No site-resolving NMR or in-vivo binding measurement; signal intensity is not a bound fraction.

nutrient_topic

Boron research collection; topical membership is not evidence of a direct dietary effect. · Boron

organism

Cell-free chemistry

plain_language

A laboratory signal suggests boron can attach to vitamin B2; this does not prove that usual boron intake depletes B2.

primary_references

[boron-p42012780] Identification of a Riboflavin-Boric Acid Complex by Electrospray Ionization Mass Spectrometry. (2026). https://pubmed.ncbi.nlm.nih.gov/42012780/ DOI: 10.1007/s12011-026-05110-9

tissue_or_cell_type

Purified riboflavin in alkaline solvent

Boron: chemistry, nutrient interactions, low-intake studies and mechanistic uncertainties (2026-09-17) · lines 183–194

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Negative-ion electrospray mass spectrometry · source_derived_draft · unverified_draft

### boron-riboflavin-adduct An additional m/z 401.3 ion was consistent with a 1:1 riboflavin–boric-acid complex in alkaline electrospray experiments; the ribityl binding site was not resolved. Condition category: normal nutrient_topic: Boron research collection; topical membership is not evidence of a direct dietary effect. plain_language: A laboratory signal suggests boron can attach to vitamin B2; this does not prove that usual boron intake depletes B2. organism: Cell-free chemistry tissue_or_cell_type: Purified riboflavin in alkaline solvent experimental_model: Negative-ion electrospray mass spectrometry limitations: Nominal mass is consistent with, but does not uniquely establish, the proposed 1:1 structure. No site-resolving NMR or in-vivo binding measurement; signal intensity is not a bound fraction. exposure: 200 µM riboflavin and 400 µM boric acid in WAT solvent at pH 10.3 evidence_span: {"source_cache": "artifacts/boron-research/42012780.fulltext.txt", "locator": "Exact primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "673f9c1649ebaea729fb8331f6394dcad15d21b7bea8e6414542210b8e9fdd69", "start_char": 6857, "end_char": 8798, "text_sha256": "09a30283b0d51a099a2687875db729353a5f03f83f616c974d75a284679f1f8f"} [boron-p42012780] Identification of a Riboflavin-Boric Acid Complex by Electrospray Ionization Mass Spectrometry. (2026). https://pubmed.ncbi.nlm.nih.gov/42012780/ DOI: 10.1007/s12011-026-05110-9

evidence_location

Abstract; intestinal fractionation and EDTA competition experiments

experimental_model

Rat mucosal fractionation, hydrolase assays and radiolabeled-riboflavin uptake in everted intestinal rings

exposure

Flavin coenzymes with or without EDTA during tracer uptake.

limitations

Rat ex vivo evidence; molecular identities of the hydrolases were not established.

nutrient_topic

Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)

organism

Rattus norvegicus

plain_language

Dietary FAD can supply absorbable riboflavin after intestinal cleavage.

primary_references

[transport-diet-1982] FMN phosphatase and FAD pyrophosphatase in rat intestinal brush borders: role in intestinal absorption of dietary riboflavin. (1982). https://doi.org/10.1093/jn/112.2.263 DOI: 10.1093/jn/112.2.263

tissue_or_cell_type

Small-intestinal mucosa

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 124–135

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rat mucosal fractionation, hydrolase assays and radiolabeled-riboflavin uptake in everted intestinal rings · source_derived_draft · unverified_draft

### transport-dietary-fad-hydrolysis Rat brush-border preparations released free riboflavin from FAD; inhibiting coenzyme hydrolysis reduced its competition with tracer riboflavin uptake. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Dietary FAD can supply absorbable riboflavin after intestinal cleavage. organism: Rattus norvegicus tissue_or_cell_type: Small-intestinal mucosa experimental_model: Rat mucosal fractionation, hydrolase assays and radiolabeled-riboflavin uptake in everted intestinal rings limitations: Rat ex vivo evidence; molecular identities of the hydrolases were not established. exposure: Flavin coenzymes with or without EDTA during tracer uptake. evidence_location: Abstract; intestinal fractionation and EDTA competition experiments [transport-diet-1982] FMN phosphatase and FAD pyrophosphatase in rat intestinal brush borders: role in intestinal absorption of dietary riboflavin. (1982). https://doi.org/10.1093/jn/112.2.263 DOI: 10.1093/jn/112.2.263

evidence_location

Abstract; intestinal fractionation and EDTA competition experiments

experimental_model

Rat mucosal fractionation, hydrolase assays and radiolabeled-riboflavin uptake in everted intestinal rings

exposure

Flavin coenzymes with or without EDTA during tracer uptake.

limitations

Rat ex vivo evidence; molecular identities of the hydrolases were not established.

nutrient_topic

Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)

organism

Rattus norvegicus

plain_language

Dietary FMN can supply absorbable riboflavin after intestinal cleavage.

primary_references

[transport-diet-1982] FMN phosphatase and FAD pyrophosphatase in rat intestinal brush borders: role in intestinal absorption of dietary riboflavin. (1982). https://doi.org/10.1093/jn/112.2.263 DOI: 10.1093/jn/112.2.263

tissue_or_cell_type

Small-intestinal mucosa

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 111–122

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rat mucosal fractionation, hydrolase assays and radiolabeled-riboflavin uptake in everted intestinal rings · source_derived_draft · unverified_draft

### transport-dietary-fmn-hydrolysis Rat brush-border preparations released free riboflavin from FMN; inhibiting coenzyme hydrolysis reduced its competition with tracer riboflavin uptake. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Dietary FMN can supply absorbable riboflavin after intestinal cleavage. organism: Rattus norvegicus tissue_or_cell_type: Small-intestinal mucosa experimental_model: Rat mucosal fractionation, hydrolase assays and radiolabeled-riboflavin uptake in everted intestinal rings limitations: Rat ex vivo evidence; molecular identities of the hydrolases were not established. exposure: Flavin coenzymes with or without EDTA during tracer uptake. evidence_location: Abstract; intestinal fractionation and EDTA competition experiments [transport-diet-1982] FMN phosphatase and FAD pyrophosphatase in rat intestinal brush borders: role in intestinal absorption of dietary riboflavin. (1982). https://doi.org/10.1093/jn/112.2.263 DOI: 10.1093/jn/112.2.263

evidence_location

Abstract and product-bound structure

experimental_model

Human RFK structural and catalytic mechanism study

exposure

Purified RFK with flavin and adenine nucleotide ligands.

limitations

Reaction chemistry does not imply RFK controls every tissue flavin pool to the same extent.

nutrient_topic

Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)

organism

Homo sapiens

plain_language

RFK performs the first activation step from riboflavin to FMN.

primary_references

[transport-rfk-2003] Ligand binding-induced conformational changes in riboflavin kinase: structural basis for the ordered mechanism. (2003). https://pubmed.ncbi.nlm.nih.gov/14580199/ DOI: 10.1021/bi035450t

tissue_or_cell_type

Purified protein

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 293–304

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human RFK structural and catalytic mechanism study · source_derived_draft · unverified_draft

### transport-rfk-phosphorylation Human RFK phosphorylates riboflavin to FMN using ATP, yielding ADP; this precedes FLAD1-mediated FAD synthesis. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: RFK performs the first activation step from riboflavin to FMN. organism: Homo sapiens tissue_or_cell_type: Purified protein experimental_model: Human RFK structural and catalytic mechanism study limitations: Reaction chemistry does not imply RFK controls every tissue flavin pool to the same extent. exposure: Purified RFK with flavin and adenine nucleotide ligands. evidence_location: Abstract and product-bound structure [transport-rfk-2003] Ligand binding-induced conformational changes in riboflavin kinase: structural basis for the ordered mechanism. (2003). https://pubmed.ncbi.nlm.nih.gov/14580199/ DOI: 10.1021/bi035450t

evidence_location

Functional characterization of hRFT1

experimental_model

Human transporter expression and radiotracer uptake

exposure

Wild-type transporter expression and radiolabeled riboflavin.

limitations

Expression-system kinetics do not establish whole-body absorption capacity.

nutrient_topic

Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)

organism

Homo sapiens

plain_language

RFVT1 carries free riboflavin into cells.

primary_references

[transport-rfvt1-2008] Identification and functional characterization of a novel human and rat riboflavin transporter, RFT1. (2008). https://doi.org/10.1152/ajpcell.00019.2008 DOI: 10.1152/ajpcell.00019.2008

tissue_or_cell_type

HEK293 and Caco-2 cells

transport_effect

raises Expression increased cellular riboflavin uptake.

transport_pool

the expressing cell Expression increased cellular riboflavin uptake.

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 137–148

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human transporter expression and radiotracer uptake · source_derived_draft · unverified_draft

### transport-rfvt1-influx Expression of human RFVT1 increased cellular riboflavin uptake in HEK293 and Caco-2 experiments. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: RFVT1 carries free riboflavin into cells. organism: Homo sapiens tissue_or_cell_type: HEK293 and Caco-2 cells experimental_model: Human transporter expression and radiotracer uptake limitations: Expression-system kinetics do not establish whole-body absorption capacity. exposure: Wild-type transporter expression and radiolabeled riboflavin. evidence_location: Functional characterization of hRFT1 [transport-rfvt1-2008] Identification and functional characterization of a novel human and rat riboflavin transporter, RFT1. (2008). https://doi.org/10.1152/ajpcell.00019.2008 DOI: 10.1152/ajpcell.00019.2008

evidence_location

Abstract; comparative HEK293 transport assays

experimental_model

Human RFVT2 expression and radiotracer uptake

exposure

Transient expression; extracellular-ion substitution.

limitations

Older name hRFT3 maps to SLC52A2, not SLC52A3; tissue mRNA enrichment is not transport flux.

nutrient_topic

Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)

organism

Homo sapiens

plain_language

RFVT2 provides a route for riboflavin entry into cells.

primary_references

[transport-rfvt2-2010] Identification and comparative functional characterization of a new human riboflavin transporter hRFT3 expressed in the brain. (2010). https://doi.org/10.3945/jn.110.122911 DOI: 10.3945/jn.110.122911

tissue_or_cell_type

HEK293 cells

transport_effect

raises Expression increased riboflavin uptake in HEK293 cells.

transport_pool

the expressing cell Expression increased riboflavin uptake in HEK293 cells.

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 150–161

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human RFVT2 expression and radiotracer uptake · source_derived_draft · unverified_draft

### transport-rfvt2-influx Human RFVT2 expression increased riboflavin uptake in HEK293 cells; uptake did not require extracellular sodium or chloride. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: RFVT2 provides a route for riboflavin entry into cells. organism: Homo sapiens tissue_or_cell_type: HEK293 cells experimental_model: Human RFVT2 expression and radiotracer uptake limitations: Older name hRFT3 maps to SLC52A2, not SLC52A3; tissue mRNA enrichment is not transport flux. exposure: Transient expression; extracellular-ion substitution. evidence_location: Abstract; comparative HEK293 transport assays [transport-rfvt2-2010] Identification and comparative functional characterization of a new human riboflavin transporter hRFT3 expressed in the brain. (2010). https://doi.org/10.3945/jn.110.122911 DOI: 10.3945/jn.110.122911

evidence_location

Figure 1c-e

experimental_model

Human RFVT3 expression and stable-isotope uptake

exposure

pH 5.5 versus 7.5; concentration-dependent [13C]riboflavin uptake.

limitations

In vitro pH comparison; not advice to alter gastrointestinal acidity.

nutrient_topic

Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)

organism

Homo sapiens

plain_language

Acidic conditions enhanced RFVT3 transport in the experiment.

primary_references

[transport-rfvt-structure-2025] Structure and transport mechanism of human riboflavin transporters (2025). https://pmc.ncbi.nlm.nih.gov/articles/PMC12044054/ DOI: 10.1038/s41467-025-59255-7

tissue_or_cell_type

HEK293T cells

transport_effect

raises Lowering extracellular pH increased RFVT3-mediated riboflavin uptake.

transport_pool

the expressing cell Lowering extracellular pH increased RFVT3-mediated riboflavin uptake.

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 241–252

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human RFVT3 expression and stable-isotope uptake · source_derived_draft · unverified_draft

### transport-rfvt3-low-ph Lowering extracellular pH from 7.5 to 5.5 increased RFVT3-mediated riboflavin uptake and changed its apparent kinetic parameters. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Acidic conditions enhanced RFVT3 transport in the experiment. organism: Homo sapiens tissue_or_cell_type: HEK293T cells experimental_model: Human RFVT3 expression and stable-isotope uptake limitations: In vitro pH comparison; not advice to alter gastrointestinal acidity. exposure: pH 5.5 versus 7.5; concentration-dependent [13C]riboflavin uptake. evidence_location: Figure 1c-e [transport-rfvt-structure-2025] Structure and transport mechanism of human riboflavin transporters (2025). https://pmc.ncbi.nlm.nih.gov/articles/PMC12044054/ DOI: 10.1038/s41467-025-59255-7

evidence_location

Figure 3C-E

experimental_model

HEK293 expression; HPLC measurement of flavin uptake

exposure

10 micromolar flavin, pH 7.4, 10 minutes, 37 C.

limitations

Substrate preference under these conditions is not proof of zero FMN transport at every concentration.

nutrient_topic

Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)

organism

Homo sapiens

plain_language

Free riboflavin was the preferred transported flavin.

primary_references

[transport-rfvt3-2014] Functional involvement of RFVT3/SLC52A3 in intestinal riboflavin absorption. (2014). https://doi.org/10.1152/ajpgi.00349.2013 DOI: 10.1152/ajpgi.00349.2013

tissue_or_cell_type

HEK293 cells

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 228–239

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · HEK293 expression; HPLC measurement of flavin uptake · source_derived_draft · unverified_draft

### transport-rfvt3-substrate-discrimination RFVT3-expressing HEK293 cells transported riboflavin strongly, FMN weakly, and showed no measurable FAD transport in the reported assay. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Free riboflavin was the preferred transported flavin. organism: Homo sapiens tissue_or_cell_type: HEK293 cells experimental_model: HEK293 expression; HPLC measurement of flavin uptake limitations: Substrate preference under these conditions is not proof of zero FMN transport at every concentration. exposure: 10 micromolar flavin, pH 7.4, 10 minutes, 37 C. evidence_location: Figure 3C-E [transport-rfvt3-2014] Functional involvement of RFVT3/SLC52A3 in intestinal riboflavin absorption. (2014). https://doi.org/10.1152/ajpgi.00349.2013 DOI: 10.1152/ajpgi.00349.2013

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/biotin-research/37085971.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "981b9e33d62aaeda20905c76b8da3a96b2d5d8184a707beed7de5f66498974b5", "start_char": 0, "end_char": 1081, "text_sha256": "981b9e33d62aaeda20905c76b8da3a96b2d5d8184a707beed7de5f66498974b5"}

experimental_model

Case report of extremely premature twins during a parenteral multivitamin shortage

exposure

Combined B2 and B7 deficiency on prolonged parenteral nutrition

limitations

Two highly vulnerable infants and multiple concurrent problems; improvement after combined treatment cannot be attributed to biotin alone.

nutrient_topic

Biotin research collection; topical membership is not evidence of a direct dietary effect. · Biotin

organism

Homo sapiens

plain_language

The case illustrates interacting shortages, without identifying which vitamin caused each finding.

primary_references

[b7-p37085971] Twin Premature Infants With Riboflavin and Biotin Deficiency Presenting With Refractory Lactic Acidosis, Rash, and Multiorgan Failure During Prolonged Parenteral Nutrition. (2023). https://pubmed.ncbi.nlm.nih.gov/37085971/ DOI: 10.1177/23247096231168111

tissue_or_cell_type

Multisystem neonatal illness

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Biotin: carboxylases, recycling, deficiency and nutrient interactions (2026-09-17) · lines 1040–1051

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Case report of extremely premature twins during a parenteral multivitamin shortage · source_derived_draft · unverified_draft

### b7-combined-b2-b7 Premature twins on vitamin-limited parenteral nutrition developed severe illness associated with B2/B7 deficiency; the surviving twin improved after both vitamins were supplied. Condition category: nutrient_deficiency nutrient_topic: Biotin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The case illustrates interacting shortages, without identifying which vitamin caused each finding. organism: Homo sapiens tissue_or_cell_type: Multisystem neonatal illness experimental_model: Case report of extremely premature twins during a parenteral multivitamin shortage limitations: Two highly vulnerable infants and multiple concurrent problems; improvement after combined treatment cannot be attributed to biotin alone. exposure: Combined B2 and B7 deficiency on prolonged parenteral nutrition evidence_span: {"source_cache": "artifacts/biotin-research/37085971.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "981b9e33d62aaeda20905c76b8da3a96b2d5d8184a707beed7de5f66498974b5", "start_char": 0, "end_char": 1081, "text_sha256": "981b9e33d62aaeda20905c76b8da3a96b2d5d8184a707beed7de5f66498974b5"} [b7-p37085971] Twin Premature Infants With Riboflavin and Biotin Deficiency Presenting With Refractory Lactic Acidosis, Rash, and Multiorgan Failure During Prolonged Parenteral Nutrition. (2023). https://pubmed.ncbi.nlm.nih.gov/37085971/ DOI: 10.1177/23247096231168111

cross_nutrient

true

evidence_location

Primary Results, wild-type structure and cofactor-binding sites; Methods flavin extraction/HPLC.

experimental_model

Human POR structure and flavin-content analysis

exposure

Recombinant N-terminally truncated human POR; X-ray structure and HPLC flavin assays.

limitations

The structural study did not measure vitamin D outcomes after riboflavin dosing; linkage to CYP2R1 comes from the separate direct reconstitution record.

nutrient

Vitamin D2 and D3 · Vitamin D2 and D3

nutrient_topic

Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin D2 and D3

organism

Homo sapiens protein

plain_language

POR carries a FAD cofactor derived from vitamin B2.

primary_references

[xia2011] Structural basis for human NADPH-cytochrome P450 oxidoreductase deficiency. (2011). https://pubmed.ncbi.nlm.nih.gov/21808038/ DOI: 10.1073/pnas.1106632108

tissue_or_cell_type

POR cofactor-binding domain

Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 407–420

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human POR structure and flavin-content analysis · source_derived_draft · unverified_draft

### vd-act-por-fad Crystallography and extracted-flavin analysis identified FAD bound to recombinant human POR. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: POR carries a FAD cofactor derived from vitamin B2. organism: Homo sapiens protein tissue_or_cell_type: POR cofactor-binding domain experimental_model: Human POR structure and flavin-content analysis limitations: The structural study did not measure vitamin D outcomes after riboflavin dosing; linkage to CYP2R1 comes from the separate direct reconstitution record. exposure: Recombinant N-terminally truncated human POR; X-ray structure and HPLC flavin assays. cross_nutrient: true evidence_location: Primary Results, wild-type structure and cofactor-binding sites; Methods flavin extraction/HPLC. nutrient: Vitamin D2 and D3 [xia2011] Structural basis for human NADPH-cytochrome P450 oxidoreductase deficiency. (2011). https://pubmed.ncbi.nlm.nih.gov/21808038/ DOI: 10.1073/pnas.1106632108

cross_nutrient

true

evidence_location

Primary Results, wild-type structure and cofactor-binding sites; Methods flavin extraction/HPLC.

experimental_model

Human POR structure and flavin-content analysis

exposure

Recombinant N-terminally truncated human POR; X-ray structure and HPLC flavin assays.

limitations

The structural study did not measure vitamin D outcomes after riboflavin dosing; linkage to CYP2R1 comes from the separate direct reconstitution record.

nutrient

Vitamin D2 and D3 · Vitamin D2 and D3

nutrient_topic

Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin D2 and D3

organism

Homo sapiens protein

plain_language

POR carries a FMN cofactor derived from vitamin B2.

primary_references

[xia2011] Structural basis for human NADPH-cytochrome P450 oxidoreductase deficiency. (2011). https://pubmed.ncbi.nlm.nih.gov/21808038/ DOI: 10.1073/pnas.1106632108

tissue_or_cell_type

POR cofactor-binding domain

Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 422–435

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human POR structure and flavin-content analysis · source_derived_draft · unverified_draft

### vd-act-por-fmn Crystallography and extracted-flavin analysis identified FMN bound to recombinant human POR. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: POR carries a FMN cofactor derived from vitamin B2. organism: Homo sapiens protein tissue_or_cell_type: POR cofactor-binding domain experimental_model: Human POR structure and flavin-content analysis limitations: The structural study did not measure vitamin D outcomes after riboflavin dosing; linkage to CYP2R1 comes from the separate direct reconstitution record. exposure: Recombinant N-terminally truncated human POR; X-ray structure and HPLC flavin assays. cross_nutrient: true evidence_location: Primary Results, wild-type structure and cofactor-binding sites; Methods flavin extraction/HPLC. nutrient: Vitamin D2 and D3 [xia2011] Structural basis for human NADPH-cytochrome P450 oxidoreductase deficiency. (2011). https://pubmed.ncbi.nlm.nih.gov/21808038/ DOI: 10.1073/pnas.1106632108

cross_nutrient

B1 performs E1 carbon chemistry; B2-derived FAD and the niacin-related NAD cofactor participate in the separate shared E3 reaction.

evidence

[{"paper_key": "brautigam-2005-dld", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract"], "locator": "Primary publication abstract", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}]

experimental_model

Human DLD crystallography with NAD+ and NADH.

limitations

Cofactor chemistry does not establish dietary B2/B3 limitation or prove rescue of B1 deficiency.

nutrient

Thiamine (vitamin B1) · Thiamine (vitamin B1)

nutrient_topic

Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)

organism

Homo sapiens

plain_language

The shared E3 protein resets reduced lipoyl carriers using the B2-derived flavin and B3-related NAD system, allowing another round of B1-dependent turnover.

primary_references

[brautigam-2005-dld] Crystal structure of human dihydrolipoamide dehydrogenase: NAD+/NADH binding and the structural basis of disease-causing mutations (2005). https://pubmed.ncbi.nlm.nih.gov/15946682/ DOI: 10.1016/j.jmb.2005.05.014

tissue_or_cell_type

Purified enzyme

Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 717–729

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human DLD crystallography with NAD+ and NADH. · source_derived_draft · unverified_draft

### b1-dld-fad-nad-lipoyl-regeneration Human DLD uses bound FAD and transiently bound NAD+ to oxidize dihydrolipoamide; NADH-bound structures place its nicotinamide ring beside FAD. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The shared E3 protein resets reduced lipoyl carriers using the B2-derived flavin and B3-related NAD system, allowing another round of B1-dependent turnover. organism: Homo sapiens tissue_or_cell_type: Purified enzyme experimental_model: Human DLD crystallography with NAD+ and NADH. limitations: Cofactor chemistry does not establish dietary B2/B3 limitation or prove rescue of B1 deficiency. evidence: [{"paper_key": "brautigam-2005-dld", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract"], "locator": "Primary publication abstract", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}] cross_nutrient: B1 performs E1 carbon chemistry; B2-derived FAD and the niacin-related NAD cofactor participate in the separate shared E3 reaction. nutrient: Thiamine (vitamin B1) [brautigam-2005-dld] Crystal structure of human dihydrolipoamide dehydrogenase: NAD+/NADH binding and the structural basis of disease-causing mutations (2005). https://pubmed.ncbi.nlm.nih.gov/15946682/ DOI: 10.1016/j.jmb.2005.05.014

cross_nutrient

B2 activation and Mg-dependent FAD synthesis provide a biochemical partner to B1-dependent complexes; direct transfer of newly made FAD to DLD was not tested.

evidence

[{"paper_key": "brizio-2006-fad", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract"], "locator": "Primary publication abstract", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}]

experimental_model

Recombinant human FLAD1 isoforms expressed in E. coli.

limitations

No tissue Mg threshold or combined B1/B2 deficiency experiment.

nutrient

Thiamine (vitamin B1) · Thiamine (vitamin B1)

nutrient_topic

Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)

organism

Homo sapiens

plain_language

The flavin used by E3 must first be made from the riboflavin pathway. This distinct magnesium-dependent synthesis reaction should not be confused with magnesium binding to B1 enzymes.

primary_references

[brizio-2006-fad] Over-expression in Escherichia coli and characterization of two recombinant isoforms of human FAD synthetase (2006). https://pubmed.ncbi.nlm.nih.gov/16643857/ DOI: 10.1016/j.bbrc.2006.04.003

tissue_or_cell_type

Purified/expressed proteins

Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 745–757

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human FLAD1 isoforms expressed in E. coli. · source_derived_draft · unverified_draft

### b1-fad-b2-cofactor-synthesis Recombinant human FLAD1 isoforms 1 and 2 exhibited FAD synthetase activity; isoform 2 was purified, and activity required MgCl2. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The flavin used by E3 must first be made from the riboflavin pathway. This distinct magnesium-dependent synthesis reaction should not be confused with magnesium binding to B1 enzymes. organism: Homo sapiens tissue_or_cell_type: Purified/expressed proteins experimental_model: Recombinant human FLAD1 isoforms expressed in E. coli. limitations: No tissue Mg threshold or combined B1/B2 deficiency experiment. evidence: [{"paper_key": "brizio-2006-fad", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract"], "locator": "Primary publication abstract", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}] cross_nutrient: B2 activation and Mg-dependent FAD synthesis provide a biochemical partner to B1-dependent complexes; direct transfer of newly made FAD to DLD was not tested. nutrient: Thiamine (vitamin B1) [brizio-2006-fad] Over-expression in Escherichia coli and characterization of two recombinant isoforms of human FAD synthetase (2006). https://pubmed.ncbi.nlm.nih.gov/16643857/ DOI: 10.1016/j.bbrc.2006.04.003

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

Documented failure of iron response in a specific induced B2-deficiency setting.

experimental_model

Historical induced-depletion study in six men with inoperable cancers; no healthy randomized control group.

exposure

Low-riboflavin semisynthetic diet plus galactoflavin antagonist, followed by riboflavin replacement; three also received oral antibiotics.

limitations

Two cases within a six-person cancer/galactoflavin experiment; cannot generalize this to every anemia or infer a modern treatment regimen.

nutrient_topic

Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)

organism

Homo sapiens

plain_language

More iron did not restore new red-cell production while usable B2 was severely limited in these cases.

primary_references

[b2-lane1964] THE RAPID INDUCTION OF HUMAN RIBOFLAVIN DEFICIENCY WITH GALACTOFLAVIN (1964). https://pubmed.ncbi.nlm.nih.gov/14135487/ DOI: 10.1172/jci104921

tissue_or_cell_type

Circulating reticulocytes

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1814–1825

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Historical induced-depletion study in six men with inoperable cancers; no healthy randomized control group. · source_derived_draft · unverified_draft

### b2-induced-iron-response-failure In two patients with induced B2 deficiency, parenteral iron did not trigger reticulocytosis, whereas subsequent riboflavin did. Condition category: nutrient_deficiency nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: More iron did not restore new red-cell production while usable B2 was severely limited in these cases. organism: Homo sapiens tissue_or_cell_type: Circulating reticulocytes experimental_model: Historical induced-depletion study in six men with inoperable cancers; no healthy randomized control group. limitations: Two cases within a six-person cancer/galactoflavin experiment; cannot generalize this to every anemia or infer a modern treatment regimen. exposure: Low-riboflavin semisynthetic diet plus galactoflavin antagonist, followed by riboflavin replacement; three also received oral antibiotics. cross_nutrient: Documented failure of iron response in a specific induced B2-deficiency setting. [b2-lane1964] THE RAPID INDUCTION OF HUMAN RIBOFLAVIN DEFICIENCY WITH GALACTOFLAVIN (1964). https://pubmed.ncbi.nlm.nih.gov/14135487/ DOI: 10.1172/jci104921

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_spans

[{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMID22611163", "locator": "metadata.abstractText", "paragraph_index": 0, "char_start": 0, "char_end": 1899, "evidence_access": "primary-abstract"}]

experimental_model

Human HEK-293 cells expressing patient-associated ETF-QO variants under varied riboflavin and temperature.

exposure

Variant expression with supplemented riboflavin, comparing clinical response groups.

limitations

Response-associated molecular comparison; no dose recommendation and no claim that all missense variants respond.

nutrient_topic

Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)

organism

Homo sapiens

plain_language

Different inherited changes left different amounts of rescuable protein function.

primary_references

[cornelius-2012-etfdh-rescue] Molecular mechanisms of riboflavin responsiveness in patients with ETF-QO variations and multiple acyl-CoA dehydrogenation deficiency (2012). https://pubmed.ncbi.nlm.nih.gov/22611163/ DOI: 10.1093/hmg/dds175

tissue_or_cell_type

HEK-293 expression system

trigger_kind

machinery_impairment Imported condition classification; unverified.

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 821–832

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human HEK-293 cells expressing patient-associated ETF-QO variants under varied riboflavin and temperature. · source_derived_draft · unverified_draft

### b2-met-etfdh-responsive-milder-folding Under the same supplemented culture conditions, ETF-QO variants linked to riboflavin-responsive MADD exhibited milder folding defects than the nonresponsive or partly responsive variants. Condition category: machinery_impairment nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Different inherited changes left different amounts of rescuable protein function. organism: Homo sapiens tissue_or_cell_type: HEK-293 expression system experimental_model: Human HEK-293 cells expressing patient-associated ETF-QO variants under varied riboflavin and temperature. limitations: Response-associated molecular comparison; no dose recommendation and no claim that all missense variants respond. exposure: Variant expression with supplemented riboflavin, comparing clinical response groups. evidence_spans: [{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMID22611163", "locator": "metadata.abstractText", "paragraph_index": 0, "char_start": 0, "char_end": 1899, "evidence_access": "primary-abstract"}] [cornelius-2012-etfdh-rescue] Molecular mechanisms of riboflavin responsiveness in patients with ETF-QO variations and multiple acyl-CoA dehydrogenation deficiency (2012). https://pubmed.ncbi.nlm.nih.gov/22611163/ DOI: 10.1093/hmg/dds175

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_spans

[{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMID22611163", "locator": "metadata.abstractText", "paragraph_index": 0, "char_start": 0, "char_end": 1899, "evidence_access": "primary-abstract"}]

experimental_model

Human HEK-293 cells expressing patient-associated ETF-QO variants under varied riboflavin and temperature.

exposure

Clinical-response-defined ETFDH variants; supplemented culture riboflavin.

limitations

Primary abstract-level claim; variants are grouped by this study, not a universal response classifier.

nutrient_topic

Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)

organism

Homo sapiens

plain_language

Some inherited ETF-QO defects remained severe despite greater B2 supply.

primary_references

[cornelius-2012-etfdh-rescue] Molecular mechanisms of riboflavin responsiveness in patients with ETF-QO variations and multiple acyl-CoA dehydrogenation deficiency (2012). https://pubmed.ncbi.nlm.nih.gov/22611163/ DOI: 10.1093/hmg/dds175

tissue_or_cell_type

HEK-293 expression system

trigger_kind

machinery_impairment Imported condition classification; unverified.

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 808–819

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human HEK-293 cells expressing patient-associated ETF-QO variants under varied riboflavin and temperature. · source_derived_draft · unverified_draft

### b2-met-etfdh-severe-rescue-boundary ETFDH variants associated with nonresponsive or partially responsive MADD showed severe misfolding in HEK-293 cells even in riboflavin-supplemented medium. Condition category: machinery_impairment nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Some inherited ETF-QO defects remained severe despite greater B2 supply. organism: Homo sapiens tissue_or_cell_type: HEK-293 expression system experimental_model: Human HEK-293 cells expressing patient-associated ETF-QO variants under varied riboflavin and temperature. limitations: Primary abstract-level claim; variants are grouped by this study, not a universal response classifier. exposure: Clinical-response-defined ETFDH variants; supplemented culture riboflavin. evidence_spans: [{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMID22611163", "locator": "metadata.abstractText", "paragraph_index": 0, "char_start": 0, "char_end": 1899, "evidence_access": "primary-abstract"}] [cornelius-2012-etfdh-rescue] Molecular mechanisms of riboflavin responsiveness in patients with ETF-QO variations and multiple acyl-CoA dehydrogenation deficiency (2012). https://pubmed.ncbi.nlm.nih.gov/22611163/ DOI: 10.1093/hmg/dds175

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_spans

[{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMID22611163", "locator": "metadata.abstractText", "paragraph_index": 0, "char_start": 0, "char_end": 1899, "evidence_access": "primary-abstract"}]

experimental_model

Human HEK-293 cells expressing patient-associated ETF-QO variants under varied riboflavin and temperature.

exposure

Riboflavin and temperature variation in cell-expression experiments.

limitations

Does not determine clinical outcomes during fever or response of an untested mutation.

nutrient_topic

Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)

organism

Homo sapiens

plain_language

Cofactor support did not make the altered proteins structurally normal.

primary_references

[cornelius-2012-etfdh-rescue] Molecular mechanisms of riboflavin responsiveness in patients with ETF-QO variations and multiple acyl-CoA dehydrogenation deficiency (2012). https://pubmed.ncbi.nlm.nih.gov/22611163/ DOI: 10.1093/hmg/dds175

tissue_or_cell_type

HEK-293-derived variant ETF-QO assays

trigger_kind

machinery_impairment Imported condition classification; unverified.

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 834–845

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human HEK-293 cells expressing patient-associated ETF-QO variants under varied riboflavin and temperature. · source_derived_draft · unverified_draft

### b2-met-etfdh-thermal-rescue-limit Residual low thermal stability of the studied ETF-QO variants indicated that FAD availability did not fully correct their structural defects. Condition category: machinery_impairment nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Cofactor support did not make the altered proteins structurally normal. organism: Homo sapiens tissue_or_cell_type: HEK-293-derived variant ETF-QO assays experimental_model: Human HEK-293 cells expressing patient-associated ETF-QO variants under varied riboflavin and temperature. limitations: Does not determine clinical outcomes during fever or response of an untested mutation. exposure: Riboflavin and temperature variation in cell-expression experiments. evidence_spans: [{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMID22611163", "locator": "metadata.abstractText", "paragraph_index": 0, "char_start": 0, "char_end": 1899, "evidence_access": "primary-abstract"}] [cornelius-2012-etfdh-rescue] Molecular mechanisms of riboflavin responsiveness in patients with ETF-QO variations and multiple acyl-CoA dehydrogenation deficiency (2012). https://pubmed.ncbi.nlm.nih.gov/22611163/ DOI: 10.1093/hmg/dds175

availability_state

nutrient_deficiency Imported condition classification; unverified.

experimental_model

Double-blind controlled trial in 60 lactating women from two Gambian villages and their infants.

exposure

Maternal 2 mg/day riboflavin or placebo for 12 weeks; background intake about 0.5 mg/day; supplementation-withdrawal observations.

limitations

Supports maternal-infant supply responsiveness; not proof of a developmental benefit or an independently measured transport mechanism.

nutrient_topic

Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)

organism

Homo sapiens

plain_language

The infant marker improved while maternal B2 was supplied and worsened again after it stopped.

primary_references

[b2-bates1982] Riboflavin requirements of lactating Gambian women: a controlled supplementation trial (1982). https://pubmed.ncbi.nlm.nih.gov/7072623/ DOI: 10.1093/ajcn/35.4.701

tissue_or_cell_type

Infant erythrocytes in maternal lactation trial

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1777–1787

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Double-blind controlled trial in 60 lactating women from two Gambian villages and their infants. · source_derived_draft · unverified_draft

### b2-milk-infant-marker-response Infants of supplemented mothers had lower activation coefficients; maternal and infant values rose toward placebo levels after supplement withdrawal. Condition category: nutrient_deficiency nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The infant marker improved while maternal B2 was supplied and worsened again after it stopped. organism: Homo sapiens tissue_or_cell_type: Infant erythrocytes in maternal lactation trial experimental_model: Double-blind controlled trial in 60 lactating women from two Gambian villages and their infants. limitations: Supports maternal-infant supply responsiveness; not proof of a developmental benefit or an independently measured transport mechanism. exposure: Maternal 2 mg/day riboflavin or placebo for 12 weeks; background intake about 0.5 mg/day; supplementation-withdrawal observations. [b2-bates1982] Riboflavin requirements of lactating Gambian women: a controlled supplementation trial (1982). https://pubmed.ncbi.nlm.nih.gov/7072623/ DOI: 10.1093/ajcn/35.4.701

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_location

Figure 5A

experimental_model

Lactating knockout/wild-type mouse comparison with HPLC

exposure

Chow containing 12-14 mg/kg riboflavin; lactating dams.

limitations

Mouse result; magnitude depends on chow and lactation conditions.

nutrient_topic

Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)

organism

Mus musculus

plain_language

ABCG2 normally makes a major contribution to riboflavin delivery into milk.

primary_references

[transport-abcg2-2007] Multidrug transporter ABCG2/breast cancer resistance protein secretes riboflavin (vitamin B2) into milk. (2007). https://pmc.ncbi.nlm.nih.gov/articles/PMC1800714/ DOI: 10.1128/MCB.01621-06

tissue_or_cell_type

Mammary milk

trigger_kind

machinery_impairment Imported condition classification; unverified.

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 544–555

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Lactating knockout/wild-type mouse comparison with HPLC · source_derived_draft · unverified_draft

### transport-abcg2-milk-riboflavin Abcg2-null dams had approximately 63-fold lower free riboflavin in milk than wild type on standard chow. Condition category: machinery_impairment nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: ABCG2 normally makes a major contribution to riboflavin delivery into milk. organism: Mus musculus tissue_or_cell_type: Mammary milk experimental_model: Lactating knockout/wild-type mouse comparison with HPLC limitations: Mouse result; magnitude depends on chow and lactation conditions. exposure: Chow containing 12-14 mg/kg riboflavin; lactating dams. evidence_location: Figure 5A [transport-abcg2-2007] Multidrug transporter ABCG2/breast cancer resistance protein secretes riboflavin (vitamin B2) into milk. (2007). https://pmc.ncbi.nlm.nih.gov/articles/PMC1800714/ DOI: 10.1128/MCB.01621-06

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_location

Effect of loss of RFVT-3 on intestinal RF uptake

experimental_model

Conditional knockout with in vivo loops and isolated enterocytes

exposure

Intestinal Slc52a3 deletion versus littermate controls.

limitations

Residual uptake and species differences limit generalization.

nutrient_topic

Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)

organism

Mus musculus

plain_language

Loss of intestinal RFVT3 restricts riboflavin absorption.

primary_references

[transport-intestinal-ko-2016] Conditional (intestinal-specific) knockout of the riboflavin transporter-3 (RFVT-3) impairs riboflavin absorption. (2016). https://pubmed.ncbi.nlm.nih.gov/26660539/ DOI: 10.1152/ajpgi.00340.2015

tissue_or_cell_type

Jejunum, colon and isolated intestinal epithelium

trigger_kind

machinery_impairment Imported condition classification; unverified.

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 267–278

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Conditional knockout with in vivo loops and isolated enterocytes · source_derived_draft · unverified_draft

### transport-intestinal-ko-uptake Intestine-specific Slc52a3 deletion severely reduced carrier-mediated riboflavin uptake in mouse jejunal/colonic loops and isolated enterocytes. Condition category: machinery_impairment nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Loss of intestinal RFVT3 restricts riboflavin absorption. organism: Mus musculus tissue_or_cell_type: Jejunum, colon and isolated intestinal epithelium experimental_model: Conditional knockout with in vivo loops and isolated enterocytes limitations: Residual uptake and species differences limit generalization. exposure: Intestinal Slc52a3 deletion versus littermate controls. evidence_location: Effect of loss of RFVT-3 on intestinal RF uptake [transport-intestinal-ko-2016] Conditional (intestinal-specific) knockout of the riboflavin transporter-3 (RFVT-3) impairs riboflavin absorption. (2016). https://pubmed.ncbi.nlm.nih.gov/26660539/ DOI: 10.1152/ajpgi.00340.2015

evidence_location

Figure 4g-l and discussion

experimental_model

Purified human transporter proteoliposomes and mutagenesis

exposure

Riboflavin addition with proton-sensitive 9-aminoacridine readout.

limitations

Proton/riboflavin stoichiometry and exact residue-specific transport steps remain unresolved.

nutrient_topic

Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)

organism

Homo sapiens protein in reconstituted membranes

plain_language

RFVT3 can connect riboflavin transport with proton movement.

primary_references

[transport-rfvt-structure-2025] Structure and transport mechanism of human riboflavin transporters (2025). https://pmc.ncbi.nlm.nih.gov/articles/PMC12044054/ DOI: 10.1038/s41467-025-59255-7

tissue_or_cell_type

Cell-free proteoliposomes

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 254–265

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human transporter proteoliposomes and mutagenesis · source_derived_draft · unverified_draft

### transport-rfvt3-proton-coupling Purified RFVT3 proteoliposomes showed riboflavin-associated proton influx; D119/E145 mutagenesis identified determinants of pH-sensitive transport. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: RFVT3 can connect riboflavin transport with proton movement. organism: Homo sapiens protein in reconstituted membranes tissue_or_cell_type: Cell-free proteoliposomes experimental_model: Purified human transporter proteoliposomes and mutagenesis limitations: Proton/riboflavin stoichiometry and exact residue-specific transport steps remain unresolved. exposure: Riboflavin addition with proton-sensitive 9-aminoacridine readout. evidence_location: Figure 4g-l and discussion [transport-rfvt-structure-2025] Structure and transport mechanism of human riboflavin transporters (2025). https://pmc.ncbi.nlm.nih.gov/articles/PMC12044054/ DOI: 10.1038/s41467-025-59255-7

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_location

RFVT3 siRNA experiment

experimental_model

T84 siRNA and apical tracer-uptake assay

exposure

RFVT3-specific siRNA compared with control siRNA.

limitations

Partial gene silencing in cultured cells; other uptake routes remain possible.

nutrient_topic

Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)

organism

Homo sapiens

plain_language

Reducing RFVT3 lowers intestinal-cell riboflavin uptake.

primary_references

[transport-rfvt3-2014] Functional involvement of RFVT3/SLC52A3 in intestinal riboflavin absorption. (2014). https://doi.org/10.1152/ajpgi.00349.2013 DOI: 10.1152/ajpgi.00349.2013

tissue_or_cell_type

Intestinal epithelial T84 cells

trigger_kind

machinery_impairment Imported condition classification; unverified.

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 215–226

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · T84 siRNA and apical tracer-uptake assay · source_derived_draft · unverified_draft

### transport-rfvt3-silencing RFVT3-directed siRNA decreased apical radiolabeled-riboflavin uptake by human T84 epithelial cells. Condition category: machinery_impairment nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Reducing RFVT3 lowers intestinal-cell riboflavin uptake. organism: Homo sapiens tissue_or_cell_type: Intestinal epithelial T84 cells experimental_model: T84 siRNA and apical tracer-uptake assay limitations: Partial gene silencing in cultured cells; other uptake routes remain possible. exposure: RFVT3-specific siRNA compared with control siRNA. evidence_location: RFVT3 siRNA experiment [transport-rfvt3-2014] Functional involvement of RFVT3/SLC52A3 in intestinal riboflavin absorption. (2014). https://doi.org/10.1152/ajpgi.00349.2013 DOI: 10.1152/ajpgi.00349.2013

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_location

Figure 5C

experimental_model

Stable-isotope riboflavin uptake in isolated muscle mitochondria

exposure

10 micromolar labeled riboflavin.

limitations

The identity of the preserved riboflavin-entry route was not established.

nutrient_topic

Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)

organism

Mus musculus

plain_language

A mitochondrial FAD transport defect need not be a free-riboflavin import defect.

primary_references

[transport-slc25a32-2022] Mitochondrial FAD shortage in SLC25A32 deficiency affects folate-mediated one-carbon metabolism. (2022). https://pmc.ncbi.nlm.nih.gov/articles/PMC11072207/ DOI: 10.1007/s00018-022-04404-0

tissue_or_cell_type

Skeletal-muscle mitochondria

trigger_kind

machinery_impairment Imported condition classification; unverified.

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 503–514

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Stable-isotope riboflavin uptake in isolated muscle mitochondria · source_derived_draft · unverified_draft

### transport-slc25a32-riboflavin-selectivity The tested Slc25a32 mutant muscle mitochondria did not show impaired uptake of isotope-labeled free riboflavin. Condition category: machinery_impairment nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A mitochondrial FAD transport defect need not be a free-riboflavin import defect. organism: Mus musculus tissue_or_cell_type: Skeletal-muscle mitochondria experimental_model: Stable-isotope riboflavin uptake in isolated muscle mitochondria limitations: The identity of the preserved riboflavin-entry route was not established. exposure: 10 micromolar labeled riboflavin. evidence_location: Figure 5C [transport-slc25a32-2022] Mitochondrial FAD shortage in SLC25A32 deficiency affects folate-mediated one-carbon metabolism. (2022). https://pmc.ncbi.nlm.nih.gov/articles/PMC11072207/ DOI: 10.1007/s00018-022-04404-0

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_location

Figure 2a

experimental_model

Transient transporter expression with radiotracer uptake

exposure

10 nM [3H]riboflavin, 1 minute, pH 7.4, 37 C.

limitations

Single-variant expression does not reproduce all neural tissue effects.

nutrient_topic

Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)

organism

Homo sapiens

plain_language

The disease-associated transporter variant imports less riboflavin.

primary_references

[transport-slc52a2-disease-2012] Impaired riboflavin transport due to missense mutations in SLC52A2 causes Brown-Vialetto-Van Laere syndrome (2012). https://pmc.ncbi.nlm.nih.gov/articles/PMC3470687/ DOI: 10.1007/s10545-012-9513-y

tissue_or_cell_type

HEK293 cells

trigger_kind

machinery_impairment Imported condition classification; unverified.

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 425–436

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Transient transporter expression with radiotracer uptake · source_derived_draft · unverified_draft

### transport-slc52a2-l123p-uptake SLC52A2 L123P variant decreased radiolabeled-riboflavin uptake compared with wild-type RFVT2 in transfected HEK293 cells. Condition category: machinery_impairment nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The disease-associated transporter variant imports less riboflavin. organism: Homo sapiens tissue_or_cell_type: HEK293 cells experimental_model: Transient transporter expression with radiotracer uptake limitations: Single-variant expression does not reproduce all neural tissue effects. exposure: 10 nM [3H]riboflavin, 1 minute, pH 7.4, 37 C. evidence_location: Figure 2a [transport-slc52a2-disease-2012] Impaired riboflavin transport due to missense mutations in SLC52A2 causes Brown-Vialetto-Van Laere syndrome (2012). https://pmc.ncbi.nlm.nih.gov/articles/PMC3470687/ DOI: 10.1007/s10545-012-9513-y

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_location

Figure 2a

experimental_model

Transient transporter expression with radiotracer uptake

exposure

10 nM [3H]riboflavin, 1 minute, pH 7.4, 37 C.

limitations

Single-variant expression does not reproduce all neural tissue effects.

nutrient_topic

Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)

organism

Homo sapiens

plain_language

The disease-associated transporter variant imports less riboflavin.

primary_references

[transport-slc52a2-disease-2012] Impaired riboflavin transport due to missense mutations in SLC52A2 causes Brown-Vialetto-Van Laere syndrome (2012). https://pmc.ncbi.nlm.nih.gov/articles/PMC3470687/ DOI: 10.1007/s10545-012-9513-y

tissue_or_cell_type

HEK293 cells

trigger_kind

machinery_impairment Imported condition classification; unverified.

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 438–449

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Transient transporter expression with radiotracer uptake · source_derived_draft · unverified_draft

### transport-slc52a2-l339p-uptake SLC52A2 L339P variant decreased radiolabeled-riboflavin uptake compared with wild-type RFVT2 in transfected HEK293 cells. Condition category: machinery_impairment nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The disease-associated transporter variant imports less riboflavin. organism: Homo sapiens tissue_or_cell_type: HEK293 cells experimental_model: Transient transporter expression with radiotracer uptake limitations: Single-variant expression does not reproduce all neural tissue effects. exposure: 10 nM [3H]riboflavin, 1 minute, pH 7.4, 37 C. evidence_location: Figure 2a [transport-slc52a2-disease-2012] Impaired riboflavin transport due to missense mutations in SLC52A2 causes Brown-Vialetto-Van Laere syndrome (2012). https://pmc.ncbi.nlm.nih.gov/articles/PMC3470687/ DOI: 10.1007/s10545-012-9513-y

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_location

Table 3 and Methods/results

experimental_model

Single genetic case; plasma flavin assay

exposure

Pretreatment plasma measurements.

limitations

One case; normal plasma measurements are not direct measurements of neuronal flavin sufficiency.

nutrient_topic

Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)

organism

Homo sapiens

plain_language

Normal plasma flavins did not exclude a cellular transport defect.

primary_references

[transport-slc52a2-disease-2012] Impaired riboflavin transport due to missense mutations in SLC52A2 causes Brown-Vialetto-Van Laere syndrome (2012). https://pmc.ncbi.nlm.nih.gov/articles/PMC3470687/ DOI: 10.1007/s10545-012-9513-y

tissue_or_cell_type

Plasma and clinical nervous-system phenotype

trigger_kind

machinery_impairment Imported condition classification; unverified.

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 451–462

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Single genetic case; plasma flavin assay · source_derived_draft · unverified_draft

### transport-slc52a2-normal-plasma The child with compound SLC52A2 L123P/L339P variants had normal measured plasma riboflavin, FMN and FAD despite a transport-associated neurologic disorder. Condition category: machinery_impairment nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Normal plasma flavins did not exclude a cellular transport defect. organism: Homo sapiens tissue_or_cell_type: Plasma and clinical nervous-system phenotype experimental_model: Single genetic case; plasma flavin assay limitations: One case; normal plasma measurements are not direct measurements of neuronal flavin sufficiency. exposure: Pretreatment plasma measurements. evidence_location: Table 3 and Methods/results [transport-slc52a2-disease-2012] Impaired riboflavin transport due to missense mutations in SLC52A2 causes Brown-Vialetto-Van Laere syndrome (2012). https://pmc.ncbi.nlm.nih.gov/articles/PMC3470687/ DOI: 10.1007/s10545-012-9513-y

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_location

Figure 5A-B

experimental_model

HEK293 transient expression, tracer uptake and membrane immunoblot

exposure

W31S expression compared with wild type.

limitations

Crude-membrane detection does not quantify correctly oriented surface protein.

nutrient_topic

Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)

organism

Homo sapiens

plain_language

A transporter can reach the membrane yet fail to carry riboflavin.

primary_references

[transport-slc52a2-neuronopathy-2014] Treatable childhood neuronopathy caused by mutations in riboflavin transporter RFVT2 (2014). https://pmc.ncbi.nlm.nih.gov/articles/PMC3891447/ DOI: 10.1093/brain/awt315

tissue_or_cell_type

HEK293 cells

trigger_kind

machinery_impairment Imported condition classification; unverified.

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 464–475

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · HEK293 transient expression, tracer uptake and membrane immunoblot · source_derived_draft · unverified_draft

### transport-slc52a2-w31s-intrinsic-defect RFVT2 W31S abolished measurable uptake despite detectable membrane expression in the study, separating transport failure from simple protein absence. Condition category: machinery_impairment nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A transporter can reach the membrane yet fail to carry riboflavin. organism: Homo sapiens tissue_or_cell_type: HEK293 cells experimental_model: HEK293 transient expression, tracer uptake and membrane immunoblot limitations: Crude-membrane detection does not quantify correctly oriented surface protein. exposure: W31S expression compared with wild type. evidence_location: Figure 5A-B [transport-slc52a2-neuronopathy-2014] Treatable childhood neuronopathy caused by mutations in riboflavin transporter RFVT2 (2014). https://pmc.ncbi.nlm.nih.gov/articles/PMC3891447/ DOI: 10.1093/brain/awt315

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

true

experimental_model

Membrane lysates of transiently transfected or endogenously expressing cells; serum of rats fed zinc-deficient diets

exposure

Cells cultured under experimental zinc-deficient conditions; depletion method and concentrations not specified in the abstract.

limitations

Abstract-only extraction. Individual enzyme-reaction assignments, depletion concentrations/durations, quantitative effects and human clinical implications are not established here. Hydrolysis of extracellular vitamin phosphates is distinct from intracellular cofactor activation.

nutrient_topic

Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc

organism

Cell species not specified in abstract

plain_language

Low zinc availability reduced the experimental preparations’ ability to remove phosphate groups from B vitamins.

primary_references

[zinc-enz-bvitamins2024] Rate of hydrolysis of the phosphate esters of B vitamins is reduced by zinc deficiency: In vitro and in vivo. (2024). https://pubmed.ncbi.nlm.nih.gov/39279493/ DOI: 10.1096/fj.202401207r

tissue_or_cell_type

Cultured-cell membrane lysates

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 833–844

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Membrane lysates of transiently transfected or endogenously expressing cells; serum of rats fed zinc-deficient diets · source_derived_draft · unverified_draft

### zinc-enz-bvitamin-cell-hydrolysis Membrane lysates from cells cultured under zinc-deficient conditions had reduced extracellular B-vitamin phosphate-ester hydrolysis activity in the study. Condition category: nutrient_deficiency nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: Low zinc availability reduced the experimental preparations’ ability to remove phosphate groups from B vitamins. organism: Cell species not specified in abstract tissue_or_cell_type: Cultured-cell membrane lysates experimental_model: Membrane lysates of transiently transfected or endogenously expressing cells; serum of rats fed zinc-deficient diets limitations: Abstract-only extraction. Individual enzyme-reaction assignments, depletion concentrations/durations, quantitative effects and human clinical implications are not established here. Hydrolysis of extracellular vitamin phosphates is distinct from intracellular cofactor activation. exposure: Cells cultured under experimental zinc-deficient conditions; depletion method and concentrations not specified in the abstract. cross_nutrient: true [zinc-enz-bvitamins2024] Rate of hydrolysis of the phosphate esters of B vitamins is reduced by zinc deficiency: In vitro and in vivo. (2024). https://pubmed.ncbi.nlm.nih.gov/39279493/ DOI: 10.1096/fj.202401207r

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

true

experimental_model

Membrane lysates of transiently transfected or endogenously expressing cells; serum of rats fed zinc-deficient diets

exposure

Rats fed zinc-deficient diets; dietary content and duration not available in the abstract.

limitations

Abstract-only extraction. Individual enzyme-reaction assignments, depletion concentrations/durations, quantitative effects and human clinical implications are not established here. Hydrolysis of extracellular vitamin phosphates is distinct from intracellular cofactor activation. The abstract does not identify which vitamin-specific endpoints were measurable in rat serum. The full-text search extract specifically said rat-serum B6 hydrolysis could not be measured; no rat B6 reaction claim or PLP participant is imported.

nutrient_topic

Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc

organism

Rattus norvegicus

plain_language

Dietary zinc deficiency also reduced this measured enzyme activity in rat serum.

primary_references

[zinc-enz-bvitamins2024] Rate of hydrolysis of the phosphate esters of B vitamins is reduced by zinc deficiency: In vitro and in vivo. (2024). https://pubmed.ncbi.nlm.nih.gov/39279493/ DOI: 10.1096/fj.202401207r

tissue_or_cell_type

Rat serum assayed ex vivo

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 846–857

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Membrane lysates of transiently transfected or endogenously expressing cells; serum of rats fed zinc-deficient diets · source_derived_draft · unverified_draft

### zinc-enz-bvitamin-rat-hydrolysis Serum from rats fed zinc-deficient diets showed reduced B-vitamin phosphate-ester hydrolysis activity in the study. Condition category: nutrient_deficiency nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: Dietary zinc deficiency also reduced this measured enzyme activity in rat serum. organism: Rattus norvegicus tissue_or_cell_type: Rat serum assayed ex vivo experimental_model: Membrane lysates of transiently transfected or endogenously expressing cells; serum of rats fed zinc-deficient diets limitations: Abstract-only extraction. Individual enzyme-reaction assignments, depletion concentrations/durations, quantitative effects and human clinical implications are not established here. Hydrolysis of extracellular vitamin phosphates is distinct from intracellular cofactor activation. The abstract does not identify which vitamin-specific endpoints were measurable in rat serum. The full-text search extract specifically said rat-serum B6 hydrolysis could not be measured; no rat B6 reaction claim or PLP participant is imported. exposure: Rats fed zinc-deficient diets; dietary content and duration not available in the abstract. cross_nutrient: true [zinc-enz-bvitamins2024] Rate of hydrolysis of the phosphate esters of B vitamins is reduced by zinc deficiency: In vitro and in vivo. (2024). https://pubmed.ncbi.nlm.nih.gov/39279493/ DOI: 10.1096/fj.202401207r

evidence_span

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experimental_model

Poison-control case series; 14 children and adults

exposure

Poisoning-related ingestion; most increased urinary riboflavin appeared in the first 24 hours

limitations

Uncontrolled case series, not ordinary dietary exposure. Increased excretion does not alone establish tissue deficiency or the responsible molecular transport mechanism.

nutrient_topic

Boron research collection; topical membership is not evidence of a direct dietary effect. · Boron

organism

Human

plain_language

High boric-acid exposure was associated with loss of vitamin B2 into urine in this case series.

primary_references

[boron-p659962] Increased urinary riboflavin excretion resulting from boric acid ingestion. (1978). https://pubmed.ncbi.nlm.nih.gov/659962/

tissue_or_cell_type

Urine after boric-acid ingestion

Boron: chemistry, nutrient interactions, low-intake studies and mechanistic uncertainties (2026-09-17) · lines 937–948

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Poison-control case series; 14 children and adults · source_derived_draft · unverified_draft

### boron-poisoning-riboflavinuria Approximately two thirds of 14 patients evaluated after boric-acid ingestion had markedly increased urinary riboflavin excretion. Condition category: normal nutrient_topic: Boron research collection; topical membership is not evidence of a direct dietary effect. plain_language: High boric-acid exposure was associated with loss of vitamin B2 into urine in this case series. organism: Human tissue_or_cell_type: Urine after boric-acid ingestion experimental_model: Poison-control case series; 14 children and adults limitations: Uncontrolled case series, not ordinary dietary exposure. Increased excretion does not alone establish tissue deficiency or the responsible molecular transport mechanism. exposure: Poisoning-related ingestion; most increased urinary riboflavin appeared in the first 24 hours evidence_span: {"source_cache": "artifacts/boron-research/659962.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "903bb51f45f538c7ce8d0a73e5247e4619efb74ce4cd3fa8fc06f9bf108ba92f", "start_char": 0, "end_char": 696, "text_sha256": "903bb51f45f538c7ce8d0a73e5247e4619efb74ce4cd3fa8fc06f9bf108ba92f"} [boron-p659962] Increased urinary riboflavin excretion resulting from boric acid ingestion. (1978). https://pubmed.ncbi.nlm.nih.gov/659962/

availability_state

machinery_impairment Imported condition classification; unverified.

cross_nutrient

true

evidence_location

Experimental procedures and Results: CblC Has a Flavin Reductase Fold; Figure 1c

experimental_model

Recombinant human MMACHC deltaC38 biochemical assay

exposure

30–40 micromolar FMN/FAD with 200 micromolar NADPH, or photoreduced FMN

limitations

Engineered truncation and reconstitution; does not establish that riboflavin supplementation rescues MMACHC defects.

nutrient_topic

Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)

organism

Homo sapiens

plain_language

A truncated B12-processing protein could use supplied flavins to carry out this reaction.

primary_references

[koutmos-2011-flavin] Structural Basis of Multifunctionality in a Vitamin B12-processing Enzyme (2011). https://pubmed.ncbi.nlm.nih.gov/21697092/ DOI: 10.1074/jbc.M111.261370

tissue_or_cell_type

Cell-free assay

trigger_kind

machinery_impairment Imported condition classification; unverified.

Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 753–765

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human MMACHC deltaC38 biochemical assay · source_derived_draft · unverified_draft

### b12-mmachc-free-flavin-decyanation Human MMACHC residues 1–244 supported cyanocobalamin decyanation with FMN or FAD plus NADPH, without a separately supplied flavoprotein reductase; reduced FMN also supported the reaction. Condition category: machinery_impairment nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: A truncated B12-processing protein could use supplied flavins to carry out this reaction. organism: Homo sapiens tissue_or_cell_type: Cell-free assay experimental_model: Recombinant human MMACHC deltaC38 biochemical assay limitations: Engineered truncation and reconstitution; does not establish that riboflavin supplementation rescues MMACHC defects. exposure: 30–40 micromolar FMN/FAD with 200 micromolar NADPH, or photoreduced FMN cross_nutrient: true evidence_location: Experimental procedures and Results: CblC Has a Flavin Reductase Fold; Figure 1c [koutmos-2011-flavin] Structural Basis of Multifunctionality in a Vitamin B12-processing Enzyme (2011). https://pubmed.ncbi.nlm.nih.gov/21697092/ DOI: 10.1074/jbc.M111.261370

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

Riboflavin (vitamin B2) (supplied_co_nutrient); Pyridoxine (supplied_co_nutrient)

evidence_span

{"source_cache": "artifacts/niacin-clinical-sources/goldsmith1952.txt", "locator": "Primary full report; exact character range, zero-based and end-exclusive", "file_sha256": "2d4004fb5985f80c8e44909506e1aa05b6eefd838f4c28102beac30fb3092bc5", "start_char": 15452, "end_char": 16019, "text_sha256": "66c68d7739e59c3e98f30fe0757f468a7952746f7dfe082138dfa6727fa54bf4"}

experimental_model

Historical metabolic-ward restriction; seven women, with three prolonged corn-diet cases developing pellagra

exposure

Corn diet about 4.7 mg niacin and 190 mg tryptophan/day; other B-vitamin supplements; 40–135 days depending on subject; subsequent niacinamide or DL-tryptophan

limitations

Very small nonrandomized historical experiment. Diets and exposure durations differed; signs were not universal. Nitrogen balance did not prove niacin sufficiency. This does not establish a modern intake threshold or demonstrate a corn toxin.

nutrient_topic

Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)

organism

Homo sapiens

plain_language

A sore mouth can arise from different nutrient problems. The appearance alone did not identify which vitamin was lacking.

primary_references

[nia-clin-goldsmith1952] Studies of niacin requirement in man. I. Experimental pellagra in subjects on corn diets low in niacin and tryptophan. (1952). https://pubmed.ncbi.nlm.nih.gov/14938430/ DOI: 10.1172/jci102638

supplementary_evidence_spans

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tissue_or_cell_type

Skin, oral and intestinal mucosa

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 1205–1218

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Historical metabolic-ward restriction; seven women, with three prolonged corn-diet cases developing pellagra · source_derived_draft · unverified_draft

### nia-clin-pellagra-riboflavin-context Cheilosis and angular stomatitis occurred during the low-niacin/tryptophan regimen even with approximately 2 mg/day total riboflavin and supplemental pyridoxine; these lesions were not specific evidence of B2 deficiency. Condition category: nutrient_deficiency nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A sore mouth can arise from different nutrient problems. The appearance alone did not identify which vitamin was lacking. organism: Homo sapiens tissue_or_cell_type: Skin, oral and intestinal mucosa experimental_model: Historical metabolic-ward restriction; seven women, with three prolonged corn-diet cases developing pellagra limitations: Very small nonrandomized historical experiment. Diets and exposure durations differed; signs were not universal. Nitrogen balance did not prove niacin sufficiency. This does not establish a modern intake threshold or demonstrate a corn toxin. exposure: Corn diet about 4.7 mg niacin and 190 mg tryptophan/day; other B-vitamin supplements; 40–135 days depending on subject; subsequent niacinamide or DL-tryptophan cross_nutrient: Riboflavin (vitamin B2) (supplied_co_nutrient); Pyridoxine (supplied_co_nutrient) evidence_span: {"source_cache": "artifacts/niacin-clinical-sources/goldsmith1952.txt", "locator": "Primary full report; exact character range, zero-based and end-exclusive", "file_sha256": "2d4004fb5985f80c8e44909506e1aa05b6eefd838f4c28102beac30fb3092bc5", "start_char": 15452, "end_char": 16019, "text_sha256": "66c68d7739e59c3e98f30fe0757f468a7952746f7dfe082138dfa6727fa54bf4"} supplementary_evidence_spans: [{"source_cache": "artifacts/niacin-clinical-sources/goldsmith1952.txt", "start_char": 8901, "end_char": 9290, "file_sha256": "2d4004fb5985f80c8e44909506e1aa05b6eefd838f4c28102beac30fb3092bc5", "text_sha256": "59d1a659822aca95688b5e36bd07b41ea700bfbfdc92b40005acf11bd540b046", "locator": "Methods: supplied B-vitamin quantities"}, {"source_cache": "artifacts/niacin-clinical-sources/goldsmith1952.txt", "start_char": 31540, "end_char": 31811, "file_sha256": "2d4004fb5985f80c8e44909506e1aa05b6eefd838f4c28102beac30fb3092bc5", "text_sha256": "ff226f4114a9dec08a00118aa9df933b8246dc89bcf362b2569c089b511d9d3e", "locator": "Discussion: riboflavin and pyridoxine supplements"}] [nia-clin-goldsmith1952] Studies of niacin requirement in man. I. Experimental pellagra in subjects on corn diets low in niacin and tryptophan. (1952). https://pubmed.ncbi.nlm.nih.gov/14938430/ DOI: 10.1172/jci102638

cross_nutrient

true

evidence_span

{"source_cache": "artifacts/iodine-synthesis-sources/37654510.txt", "start_char": 9069, "end_char": 10489, "text_sha256": "5e0dc84da55832b58d1a1ad6c3a327551b878ef108389abf34b7eda4dcc8b7a1", "text_characters": 1420, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."}

experimental_model

Purified soluble human IYD reconstituted with FMN or synthetic 2-prime-deoxyFMN

exposure

Human IYD reconstituted with FMN or synthetic 2-prime-deoxyFMN; Table 1 kcat/Km 5.0 versus 0.97 x 10^3 M^-1 s^-1; kcat 0.052 versus 0.32 s^-1.

limitations

Synthetic cofactor substitution is not riboflavin deficiency; kcat/Km and kcat are different measurements. Table 1 native-FMN kinetic comparator is cited from previous work; reconstituted FMN was used for binding comparisons.

nutrient_topic

Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine

organism

Homo sapiens recombinant protein

plain_language

A small change to FMN weakened overall substrate processing even though the saturated enzyme turned over faster.

primary_references

[iodine-syn-iyd2023] The 2'-hydroxy group of flavin mononucleotide influences the catalytic function and promiscuity of the flavoprotein iodotyrosine dehalogenase. (2023). https://pubmed.ncbi.nlm.nih.gov/37654510/ DOI: 10.1039/d3cb00094j

tissue_or_cell_type

Purified enzyme

Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 730–742

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified soluble human IYD reconstituted with FMN or synthetic 2-prime-deoxyFMN · source_derived_draft · unverified_draft

### iodine-syn-iyd-cofactor-substitution Replacing FMN with 2-prime-deoxyFMN in human IYD lowered iodotyrosine dehalogenation efficiency by more than fivefold while increasing turnover number by more than sixfold. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: A small change to FMN weakened overall substrate processing even though the saturated enzyme turned over faster. organism: Homo sapiens recombinant protein tissue_or_cell_type: Purified enzyme experimental_model: Purified soluble human IYD reconstituted with FMN or synthetic 2-prime-deoxyFMN limitations: Synthetic cofactor substitution is not riboflavin deficiency; kcat/Km and kcat are different measurements. Table 1 native-FMN kinetic comparator is cited from previous work; reconstituted FMN was used for binding comparisons. exposure: Human IYD reconstituted with FMN or synthetic 2-prime-deoxyFMN; Table 1 kcat/Km 5.0 versus 0.97 x 10^3 M^-1 s^-1; kcat 0.052 versus 0.32 s^-1. cross_nutrient: true evidence_span: {"source_cache": "artifacts/iodine-synthesis-sources/37654510.txt", "start_char": 9069, "end_char": 10489, "text_sha256": "5e0dc84da55832b58d1a1ad6c3a327551b878ef108389abf34b7eda4dcc8b7a1", "text_characters": 1420, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."} [iodine-syn-iyd2023] The 2'-hydroxy group of flavin mononucleotide influences the catalytic function and promiscuity of the flavoprotein iodotyrosine dehalogenase. (2023). https://pubmed.ncbi.nlm.nih.gov/37654510/ DOI: 10.1039/d3cb00094j

cross_nutrient

true

evidence_span

{"source_cache": "artifacts/iodine-synthesis-sources/25395621.txt", "start_char": 14596, "end_char": 15366, "text_sha256": "5f3959109e358adaddae3ea78c716d16316c28f6fb4153ad5696bae7b1ed733e", "text_characters": 770, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."}

experimental_model

Recombinant human IYD lacking residues 1–31; crystallography, radiotracer kinetics and redox titration

exposure

Human soluble IYD crystallized alone or with 3-iodo-L-tyrosine.

limitations

Cofactor structure; no riboflavin restriction or supplementation study.

nutrient_topic

Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine

organism

Homo sapiens recombinant protein

plain_language

IYD uses the vitamin-B2-derived cofactor FMN to handle iodotyrosine.

primary_references

[iodine-syn-iyd2015] A switch between one- and two-electron chemistry of the human flavoprotein iodotyrosine deiodinase is controlled by substrate. (2015). https://pubmed.ncbi.nlm.nih.gov/25395621/ DOI: 10.1074/jbc.m114.605964

tissue_or_cell_type

Purified soluble IYD

Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 702–714

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human IYD lacking residues 1–31; crystallography, radiotracer kinetics and redox titration · source_derived_draft · unverified_draft

### iodine-syn-iyd-fmn-binding Human IYD crystal structures show one bound FMN per polypeptide, with iodotyrosine contacting its isoalloxazine ring in the substrate complex. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: IYD uses the vitamin-B2-derived cofactor FMN to handle iodotyrosine. organism: Homo sapiens recombinant protein tissue_or_cell_type: Purified soluble IYD experimental_model: Recombinant human IYD lacking residues 1–31; crystallography, radiotracer kinetics and redox titration limitations: Cofactor structure; no riboflavin restriction or supplementation study. exposure: Human soluble IYD crystallized alone or with 3-iodo-L-tyrosine. cross_nutrient: true evidence_span: {"source_cache": "artifacts/iodine-synthesis-sources/25395621.txt", "start_char": 14596, "end_char": 15366, "text_sha256": "5f3959109e358adaddae3ea78c716d16316c28f6fb4153ad5696bae7b1ed733e", "text_characters": 770, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."} [iodine-syn-iyd2015] A switch between one- and two-electron chemistry of the human flavoprotein iodotyrosine deiodinase is controlled by substrate. (2015). https://pubmed.ncbi.nlm.nih.gov/25395621/ DOI: 10.1074/jbc.m114.605964

cross_nutrient

true

evidence_span

{"source_cache": "artifacts/iodine-synthesis-sources/25395621.txt", "start_char": 4223, "end_char": 4943, "text_sha256": "5567eccc06be2559ce51e8a2640697678a8fd3c1216896997568a9341da5a73b", "text_characters": 720, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."}

experimental_model

Recombinant human IYD lacking residues 1–31; crystallography, radiotracer kinetics and redox titration

exposure

Reductive titration with versus without active-site ligand.

limitations

An inert fluorotyrosine probe demonstrates cofactor control, not physiological fluoride displacement.

nutrient_topic

Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine

organism

Homo sapiens recombinant protein

plain_language

Substrate-like binding changes which FMN redox state the enzyme can stabilize.

primary_references

[iodine-syn-iyd2015] A switch between one- and two-electron chemistry of the human flavoprotein iodotyrosine deiodinase is controlled by substrate. (2015). https://pubmed.ncbi.nlm.nih.gov/25395621/ DOI: 10.1074/jbc.m114.605964

tissue_or_cell_type

Purified soluble IYD

Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 716–728

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human IYD lacking residues 1–31; crystallography, radiotracer kinetics and redox titration · source_derived_draft · unverified_draft

### iodine-syn-iyd-redox-switch The substrate analog 3-fluoro-L-tyrosine stabilized a one-electron-reduced FMN semiquinone during reductive titration of soluble human IYD. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Substrate-like binding changes which FMN redox state the enzyme can stabilize. organism: Homo sapiens recombinant protein tissue_or_cell_type: Purified soluble IYD experimental_model: Recombinant human IYD lacking residues 1–31; crystallography, radiotracer kinetics and redox titration limitations: An inert fluorotyrosine probe demonstrates cofactor control, not physiological fluoride displacement. exposure: Reductive titration with versus without active-site ligand. cross_nutrient: true evidence_span: {"source_cache": "artifacts/iodine-synthesis-sources/25395621.txt", "start_char": 4223, "end_char": 4943, "text_sha256": "5567eccc06be2559ce51e8a2640697678a8fd3c1216896997568a9341da5a73b", "text_characters": 720, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."} [iodine-syn-iyd2015] A switch between one- and two-electron chemistry of the human flavoprotein iodotyrosine deiodinase is controlled by substrate. (2015). https://pubmed.ncbi.nlm.nih.gov/25395621/ DOI: 10.1074/jbc.m114.605964

cross_nutrient

B2-derived FAD affects folate-enzyme stability.

experimental_model

Recombinant human MTHFR; kinetics and structures.

exposure

FAD before versus after heating

limitations

Heat challenge is not physiological riboflavin deficiency.

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

Flavin protected the enzyme during heat stress.

primary_references

[froese-2018] Structural basis for the regulation of human 5,10-methylenetetrahydrofolate reductase by phosphorylation and S-adenosylmethionine inhibition (2018). https://pubmed.ncbi.nlm.nih.gov/29891918/ DOI: 10.1038/s41467-018-04735-2

tissue_or_cell_type

Purified protein

Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 447–458

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human MTHFR; kinetics and structures. · source_derived_draft · unverified_draft

### folate-methyl-fad-heat-protection FAD supplied before a 46 C, five-minute incubation preserved more MTHFR activity than FAD added after heating. Condition category: normal nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Flavin protected the enzyme during heat stress. organism: Homo sapiens tissue_or_cell_type: Purified protein experimental_model: Recombinant human MTHFR; kinetics and structures. limitations: Heat challenge is not physiological riboflavin deficiency. exposure: FAD before versus after heating cross_nutrient: B2-derived FAD affects folate-enzyme stability. [froese-2018] Structural basis for the regulation of human 5,10-methylenetetrahydrofolate reductase by phosphorylation and S-adenosylmethionine inhibition (2018). https://pubmed.ncbi.nlm.nih.gov/29891918/ DOI: 10.1038/s41467-018-04735-2