Meta Information
ID:iron-bisglycinate
Name:
Schema Version:2.4_uniform_evidence_2026_06_18
Created
2026-05-21T22:30:00Z
Model
phase-a-upgrade-claude-sonnet-4.6
Interactions
Target id:
/class/antacids
Target name:
Antacids
Severity:
major
Interaction type:
diminishing
Nature:
temporal
Temporal spacing:
Hours before target:
4
Hours after target:
4
Description:
Antacids contain minerals like calcium, magnesium, and aluminum that bind to iron in the gut, forming insoluble complexes and severely reducing its absorption.
Actionable advice:
Iron and any antacid dose should be separated by at least 4 hours.
Validation status:
validated_via_class_inference
Evidence tier:
tier_c
Evidence basis:
class_inference_summary
Evidence anchors:
Source url:
Established mechanism / class pharmacology (no single primary source quoted)
Exact phrase from label:
Mechanistic inference: antacids raise gastric pH and can form insoluble complexes with iron, reducing non-heme iron absorption; separate dosing by ~2 h. Chelated bisglycinate iron is less pH-dependent, so the effect is smaller than for iron salts.
Label source:
Class inference
Action type:
separate
Target id:
/class/chelating-antibiotics
Target name:
Tetracycline & Quinolone Antibiotics
Severity:
major
Interaction type:
diminishing
Nature:
temporal
Temporal spacing:
Hours before target:
2
Hours after target:
6
Description:
Iron binds to tetracycline and fluoroquinolone antibiotics, preventing the absorption of both the iron and the antibiotic, which can lead to treatment failure.
Actionable advice:
Iron should be taken at least 2 hours before or 6 hours after these antibiotics.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Oral antimicrobials, including ciprofloxacin, levofloxacin and doxycycline, are susceptible to binding with enteral therapies such as calcium and iron therapies. Administered together, the bioavailability of these antimicrobials is expected to be reduced.
Label source:
PubMed: Burden of enteral supplement interactions with common antimicrobial agents: a single-centre observational analysis. (PMID 33414257)
Action type:
separate
Target id:
/intervention/levothyroxine
Target name:
Levothyroxine
Severity:
major
Interaction type:
diminishing
Nature:
temporal
Temporal spacing:
Hours before target:
4
Hours after target:
4
Description:
Iron can bind to levothyroxine in the gastrointestinal tract, reducing its absorption and potentially leading to hypothyroidism.
Actionable advice:
Iron and levothyroxine doses should be separated by at least 4 hours.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Inform patients that agents such as iron and calcium supplements and antacids can decrease the absorption of levothyroxine.
Label source:
FDA label: Levothyroxine (Synthroid)
Action type:
separate
Target id:
/dietary/calcium-rich-foods
Target name:
Calcium-Rich Foods (e.g., Dairy)
Severity:
major
Interaction type:
diminishing
Nature:
temporal
Temporal spacing:
Hours before target:
2
Hours after target:
2
Description:
Calcium directly competes with iron for absorption in the small intestine, significantly reducing the amount of iron your body can utilize from a supplement.
Actionable advice:
Iron should not be taken with dairy products or calcium-fortified foods; these should be separated by at least 2 hours.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
extracellular calcium inhibits iron uptake by Caco-2 cells in a concentration-dependent manner... calcium acts as a reversible noncompetitive inhibitor of the iron transport activity of DMT1.
Label source:
PMID 36342159. Supports calcium inhibiting iron uptake. FLAG: calcium is a NONcompetitive DMT1 inhibitor - the row's wording 'directly competes' should be softened to 'inhibits.'
Action type:
separate
Target id:
/intervention/calcium-supplements
Target name:
Calcium Supplements
Severity:
major
Interaction type:
diminishing
Nature:
temporal
Temporal spacing:
Hours before target:
2
Hours after target:
4
Description:
High doses of supplemental calcium strongly inhibit the absorption of iron by competing for the same intestinal transporters.
Actionable advice:
Iron and calcium supplement doses should be separated by at least 4 hours.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
The practical nutritional implications of the inhibitory effect of calcium are considerable since addition of milk, milkshake or cheese to common meals such as pizza or hamburger meals reduced iron absorption by 50-60%.
Label source:
PubMed: European journal of clinical nutrition (1992)
Source url:
Exact phrase from label:
We found that extracellular calcium inhibits iron uptake by Caco-2 cells in a concentration-dependent manner. Chelation of intracellular calcium with BAPTA did not affect iron uptake, which indicates that the inhibitory effect of calcium is not exerted through intracellular calcium signaling.
Label source:
PubMed: American journal of physiology. Cell physiology (2022)
Source url:
Exact phrase from label:
All calcium supplements inhibited absorption of the iron supplement when taken with food. The absorption of dietary nonheme iron was also inhibited by all three supplements.
Label source:
PubMed: The American journal of clinical nutrition (1991)
Action type:
separate
Target id:
/intervention/bisphosphonates
Target name:
Bisphosphonates
Severity:
major
Interaction type:
diminishing
Nature:
temporal
Temporal spacing:
Hours before target:
2
Hours after target:
2
Description:
Iron forms a complex with bisphosphonate drugs (used for osteoporosis), which dramatically reduces their absorption and effectiveness.
Actionable advice:
Iron and bisphosphonate medications should be separated by at least 2 hours.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Instruct patients to take supplemental calcium and vitamin D if their dietary intake is inadequate; and to take calcium supplements, antacids, magnesium-based supplements or laxatives, and iron preparations at a different time of the day
Label source:
FDA label: Risedronate (Actonel)
Action type:
separate
Target id:
/condition/hemochromatosis
Target name:
Hemochromatosis (Iron Overload)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Hemochromatosis is a genetic disorder causing the body to absorb too much iron, leading to toxic accumulation in organs. Iron supplementation is strictly contraindicated.
Actionable advice:
Iron supplements should not be taken in hemochromatosis.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
These disorders include various forms of hemochromatosis, which are characterized by inadequate hepcidin production and, thus, increased dietary iron intake, and iron-loading anemias whereby both increased iron absorption and transfusion therapy contribute to the iron overload.
Label source:
PubMed: Current understanding of iron homeostasis. (PMID 29070551)
Action type:
avoid
Target id:
/condition/iron-loading-anemia
Target name:
Iron-Loading Anemias
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Conditions like thalassemia or sideroblastic anemia can lead to iron overload despite the presence of anemia. Supplementation can be dangerous and worsen organ damage.
Actionable advice:
Iron supplements should be avoided unless specifically prescribed and monitored by a hematologist.
Validation status:
validated_via_class_inference
Evidence tier:
tier_c
Evidence basis:
class_inference_summary
Evidence anchors:
Source url:
Established mechanism / class pharmacology (no single primary source quoted)
Exact phrase from label:
Textbook contraindication (class inference): in iron-loading anemias (thalassemia, sideroblastic anemia), ineffective erythropoiesis suppresses hepcidin and drives increased GI iron absorption, so iron supplementation risks overload despite anemia and should be avoided unless deficiency is documented. (Original source was a non-authoritative healthline.com page, discarded.)
Label source:
Class inference
Action type:
avoid
Target id:
/intervention/levodopa
Target name:
Levodopa
Severity:
major
Interaction type:
diminishing
Nature:
temporal
Temporal spacing:
Hours before target:
2
Hours after target:
2
Description:
Iron can chelate (bind to) levodopa in the gut, reducing its absorption and effectiveness for treating Parkinson's disease.
Actionable advice:
Doses of iron and levodopa should be separated by at least 2 hours.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Iron salts or multi vitamins containing iron salts should be coadministered with caution.
Label source:
FDA label: Carbidopa-Levodopa (Sinemet)
Action type:
separate
Target id:
/dietary/polyphenol-rich-foods
Target name:
Polyphenol-Rich Foods (Tea, Coffee)
Severity:
moderate
Interaction type:
diminishing
Nature:
temporal
Temporal spacing:
Hours before target:
1
Hours after target:
2
Description:
Polyphenols and tannins found in tea, coffee, and red wine can bind to iron, inhibiting its absorption. Iron bisglycinate is less affected than other forms but inhibition still occurs.
Actionable advice:
Tea or coffee is best avoided within 1 hour before or 2 hours after taking iron.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Polyphenolic compounds significantly inhibited heme-55Fe absorption in a dose-dependent manner.
Label source:
Ma et al. (Caco-2), PMID 22417433. Supports polyphenol/tannin inhibition of iron absorption. Note: heme-iron model; the 'bisglycinate is less affected' nuance is established chelate behavior, not from this source.
Action type:
separate
Target id:
/dietary/phytate-rich-foods
Target name:
Phytate-Rich Foods (Grains, Legumes)
Severity:
moderate
Interaction type:
diminishing
Nature:
temporal
Temporal spacing:
Hours before target:
1
Hours after target:
2
Description:
Phytic acid, found in whole grains, legumes, nuts, and seeds, can bind to iron and reduce its bioavailability, though iron bisglycinate is more resistant than iron salts.
Actionable advice:
Iron is best taken at least 1 hour before or 2 hours after meals high in phytates.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
FA is the main storage form of phosphorus in nuts, grains, legumes, and seeds, which satisfies the biosynthesis needs of growing tissues during germination. FA is known as a dietary inhibitor that chelates minerals and trace elements, limiting their bioavailability and reducing their absorption.
Label source:
PubMed: [The role of phytates in human nutrition]. (PMID 37801451)
Action type:
separate
Target id:
/class/dmt1-competing-minerals
Target name:
High-Dose Competing Minerals (Zinc, Magnesium, Manganese)
Severity:
moderate
Interaction type:
diminishing
Nature:
temporal
Temporal spacing:
Hours before target:
2
Hours after target:
2
Description:
High doses of other divalent minerals, particularly zinc, can compete with iron for absorption via the DMT1 transporter in the intestine.
Actionable advice:
High-dose zinc or magnesium supplements and iron should be separated by at least 2 hours.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Several studies showed that high iron concentrations can negatively affect zinc absorption in adults when these trace minerals are given in solution.
Label source:
Whittaker P, Am J Clin Nutr (1998), PMID 9701159. Establishes dose-dependent iron-zinc absorptive competition (bidirectional; most relevant for high-dose supplements taken in solution/between meals). NOTE: the specific DMT1-upregulation mechanism in the original claim is unconfirmed - the competition itself is the validated part.
Action type:
separate
Target id:
/class/acid-suppressors
Target name:
Gastric Acid Suppressors (PPIs, H2 Blockers)
Severity:
moderate
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Reducing stomach acid can decrease the absorption of iron. While iron bisglycinate is less dependent on acid than other forms, absorption can still be moderately reduced.
Actionable advice:
If you take acid-suppressing medication long-term, discuss your iron status with your doctor.
Validation status:
validated_via_class_inference
Evidence tier:
tier_c
Evidence basis:
class_inference_summary
Evidence anchors:
Source url:
Established mechanism / class pharmacology (no single primary source quoted)
Exact phrase from label:
Mechanistic inference: gastric acid aids reduction of ferric to absorbable ferrous iron, so PPIs/H2 blockers can lower non-heme iron absorption; chelated bisglycinate iron is less affected. Monitoring-level.
Label source:
Class inference
Action type:
informational_none
Target id:
/dietary/meal
Target name:
Any Caloric Meal
Severity:
moderate
Interaction type:
diminishing
Nature:
temporal
Temporal spacing:
Hours before target:
1
Hours after target:
2
Description:
For maximum absorption, iron should be taken on an empty stomach. Food components, even in meals without major inhibitors, can decrease its uptake.
Actionable advice:
Iron is best taken 1 hour before or 2 hours after eating for best absorption.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
In studies 2A and 2B, absorption from all sources was strongly inversely related to serum ferritin, with geometric means of 32.5% (iron ascorbate), 9.1% (bisglycinate), and 15.3% (trisglycinate).
Label source:
PubMed: The American journal of clinical nutrition (2000)
Source url:
Exact phrase from label:
Iron absorption from FeBC is affected by enhancers and inhibitors of iron absorption, but to a lesser extent than ferrous sulfate.
Label source:
PubMed: International journal for vitamin and nutrition research. Internationale Zeitschrift fur Vitamin- und Ernahrungsforschung. Journal international de vitaminologie et de nutrition (2004)
Source url:
Exact phrase from label:
In conclusion, when considering possible fortificants for optimizing Fe bioavailability within a foodstuff, it is of paramount importance to consider the interaction between the fortified foodstuffs and other components of the meal (such as milk and coffee with a breakfast).
Label source:
PubMed: The British journal of nutrition (2005)
Action type:
separate
Target id:
/circadian/wake
Target name:
Morning (Upon Waking)
Severity:
moderate
Interaction type:
synergistic
Nature:
temporal
Temporal spacing:
Hours before target:
null
Hours after target:
1
Description:
The body's primary iron-regulating hormone, hepcidin, is naturally at its lowest levels in the morning, which may allow for more efficient iron absorption.
Actionable advice:
An iron supplement is best taken in the morning on an empty stomach for potentially better results.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
In healthy individuals, hepcidin-25 concentrations displayed a diurnal variation, with concentrations being lowest in the early morning and steadily increasing throughout the day before declining during the evening hours, a pattern that was not influenced by food intake.
Label source:
PubMed: Clinical chemistry (2012)
Source url:
Exact phrase from label:
Healthy volunteers showed a diurnal increase of serum hepcidin at noon and 8 pm compared with 8 am, and a transient rise of serum hepcidin in response to iron ingestion.
Label source:
PubMed: Blood (2008)
Action type:
separate
Target id:
/condition/inflammatory-bowel-disease
Target name:
Inflammatory Bowel Disease (IBD)
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Oral iron can sometimes irritate the gastrointestinal lining and may exacerbate symptoms in active IBD. Iron bisglycinate is better tolerated but caution is still advised.
Actionable advice:
It is important to talk to a gastroenterologist before starting iron, as IV iron may be a better option.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
While oral iron is widely used, growing evidence suggests it can disrupt the gut microbiota by reducing beneficial commensal bacteria and promoting pro-inflammatory shifts in the intestinal environment. These changes may exacerbate mucosal inflammation and contribute to gastrointestinal side effects, often resulting in poor adherence.
Label source:
PubMed: Scandinavian journal of gastroenterology (2025)
Source url:
Exact phrase from label:
However, depending on the iron formulation used in the diets, iron supplementation during dextran sodium sulfate-induced colitis was either beneficial (ferrous bisglycinate) or highly detrimental (FEDTA).
Label source:
PubMed: Inflammatory bowel diseases (2017)
Source url:
Exact phrase from label:
However, its multitude of side effects, impact on the microbiome and further exacerbating IBD activity can have consequences on patient compliance. The newer oral iron formulations show promising safety and efficacy data with a good side effect profile.
Label source:
PubMed: Nutrients (2020)
Action type:
informational_none
Target id:
/intervention/vitamin-c
Target name:
Vitamin C
Severity:
minor
Interaction type:
synergistic
Nature:
temporal
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Vitamin C enhances non-heme iron absorption by keeping it in a more soluble form and can help counteract dietary inhibitors like phytates and polyphenols.
Actionable advice:
Consider taking iron with at least 250mg of Vitamin C, especially if taken near a meal.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Vitamin C enhances the absorption of dietary iron, although population-based data showing its efficacy in reducing anaemia or iron deficiency are lacking.
Label source:
PubMed: The role of vitamins in the prevention and control of anaemia. (PMID 10948381)
Action type:
informational_none
Target id:
/biomarker/iron-panel
Target name:
Iron Panel & Ferritin
Severity:
major
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
The primary purpose of iron supplementation is to raise iron levels, which is monitored via biomarkers like serum iron, ferritin, TIBC, and transferrin saturation.
Actionable advice:
Regularly monitor your iron panel and ferritin levels with your doctor to guide dosing and prevent overload.
Validation status:
validated_via_clinical_guidance
Evidence tier:
tier_b
Evidence basis:
clinical_guidance_verbatim
Evidence anchors:
Exact phrase from label:
Serum ferritin concentration, a measure of the body's iron stores, is currently the most efficient and cost-effective test for diagnosing iron deficiency... iron stores are depleted and transferrin saturation declines, but hemoglobin levels are usually within the normal range.
Label source:
NIH ODS Iron fact sheet, Assessing Iron Status. Supports ferritin + transferrin saturation monitoring of iron therapy.
Action type:
monitor