Meta Information
ID:butyrate
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:
/dietary/meal
Target name:
Any Caloric Meal
Severity:
moderate
Interaction type:
requirement
Nature:
temporal
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Butyrate is an acid and can cause gastrointestinal upset or nausea when taken on an empty stomach. Taking it with food mitigates this risk.
Actionable advice:
Butyrate supplements are best taken with a meal or a substantial snack.
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:
Practical advice: butyrate/butyric acid is acidic and can cause GI upset or reflux on an empty stomach, so taking it with food is reasonable. FLAG: the cited PMID 41499750 is an L-glufosinate HERBICIDE developmental-toxicology paper, entirely unrelated - citation is wrong; advice is practical, not a studied interaction.
Label source:
Class inference
Action type:
informational_none
Target id:
/dietary/high-fiber-meal
Target name:
High-Fiber Foods (e.g., legumes, whole grains, vegetables)
Severity:
moderate
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Dietary fiber is fermented by gut bacteria to produce endogenous butyrate, complementing the effects of supplementation and supporting overall gut health.
Actionable advice:
Consume a diet rich in fiber to naturally support butyrate production alongside supplementation.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Therapeutic strategies that restore BPB populations and butyrate levels, such as prebiotics, dietary fiber, and microbiota-targeted interventions, hold promise for mitigating inflammation and enhancing systemic health through microbiome modulation.
Label source:
Butyrate-producing-bacteria review, PMID 41683715. Supports dietary fiber being fermented to endogenous butyrate, complementing supplementation.
Action type:
informational_none
Target id:
/intervention/inulin
Target name:
Inulin (Prebiotic Fiber)
Severity:
moderate
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Prebiotic fibers like inulin serve as a substrate for gut bacteria to produce more of their own butyrate, creating a powerful synergistic effect for colon health.
Actionable advice:
Consider taking with a prebiotic fiber source to enhance both endogenous and exogenous butyrate benefits.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Except for a bifidogenic effect, ITF and AXOS also have shown to cause a butyrogenic effect in the human colon, i.e., an enhancement of colon butyrate production.
Label source:
PubMed: Bifidobacteria and Butyrate-Producing Colon Bacteria: Importance and Strategies for Their Stimulation in the Human Gut. (PMID 27446020)
Action type:
informational_none
Target id:
/intervention/probiotics
Target name:
Probiotics
Severity:
moderate
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Probiotic supplements introduce beneficial bacteria that can produce butyrate from fiber, working in concert with direct butyrate supplementation to support the gut microbiome.
Actionable advice:
This is best combined with a quality probiotic to support the entire gut health ecosystem.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
We also critically evaluate emerging microbiome-centered therapeutic strategies, including targeted probiotics, prebiotics, dietary modulation, and fecal microbiota transplantation, while addressing factors that underlie inter-individual variability in treatment responses.
Label source:
PubMed: Gut microbiome and metabolic health: mechanisms and precision interventions. (PMID 42015346)
Action type:
informational_none
Target id:
/class/antidiabetic-medications
Target name:
Diabetes Medications
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Butyrate can improve insulin sensitivity and lower blood glucose, potentially increasing the effect of diabetes medications and raising the risk of hypoglycemia (low blood sugar).
Actionable advice:
Blood glucose is best monitored closely when starting butyrate, and it is important to consult a doctor, as medication dosages may need adjustment.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Metformin decreases hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization.
Label source:
Action type:
monitor
Target id:
/intervention/metformin
Target name:
Metformin
Severity:
moderate
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Metformin can favorably alter the gut microbiome to increase butyrate-producing bacteria; co-administration may enhance the gut-mediated metabolic benefits of both compounds.
Actionable advice:
Taking butyrate with metformin may amplify shared benefits for metabolic and gut health.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Intervention: Consider the benefits and risks of concomitant use with metformin hydrochloride.
Label source:
Action type:
informational_none
Target id:
/class/glp-1-receptor-agonists
Target name:
GLP-1 Receptor Agonists
Severity:
moderate
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Butyrate naturally stimulates the release of GLP-1 from intestinal cells, potentially enhancing the effects of GLP-1 agonist medications on satiety and glucose control.
Actionable advice:
Combining with GLP-1 agonists may provide additive benefits; monitor for increased gastrointestinal side effects.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Severe gastrointestinal
adverse reactions have also been reported postmarketing with GLP-1 receptor agonists.
Label source:
Action type:
monitor
Target id:
/intervention/valproic-acid
Target name:
Valproic Acid (and other HDAC inhibitors)
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Butyrate is a natural histone deacetylase (HDAC) inhibitor. Combining it with pharmaceutical HDAC inhibitors like valproic acid could lead to excessive, unpredictable, or adverse effects.
Actionable advice:
Butyrate supplements are best avoided when taking prescription HDAC inhibitors unless directed by a physician.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Male ICR mice received 7.5 Gy TBI followed by a single administration of valproic acid (VPA; 300 or 600 mg/kg), sodium butyrate (NaB; 500 or 1000 mg/kg)
Label source:
PMID 41320313. Establishes both sodium butyrate and valproic acid as HDAC inhibitors studied together; supports the additive-HDAC-inhibition rationale (note: the combined clinical effect is an extension).
Action type:
avoid
Target id:
/class/anticoagulants-antiplatelets
Target name:
Anticoagulants and Antiplatelets
Severity:
minor
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
There is a theoretical risk based on in-vitro data that short-chain fatty acids may have mild antiplatelet effects, potentially increasing bleeding risk when combined with these medications.
Actionable advice:
This is best used with caution, and it is worth talking to a healthcare provider when on blood-thinning medication.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Some botanicals may cause bleeding events when taken alone (e.g., garlic and Ginkgo biloba) and may have anticoagulant, antiplatelet, and/or fibrinolytic properties.
Label source:
Action type:
informational_none
Target id:
/class/potassium-elevators
Target name:
Potassium-Elevating Drugs (ACEi, ARBs, K-Sparing Diuretics)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Potassium butyrate supplements can significantly increase potassium intake, leading to a dangerous risk of hyperkalemia (high blood potassium) when combined with medications that also raise potassium.
Actionable advice:
Potassium butyrate should be avoided with ACE inhibitors, ARBs, or potassium-sparing diuretics, and a different salt form is preferable.
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: potassium butyrate salts add to potassium intake, which is plausibly additive with potassium-elevating drugs and could raise hyperkalemia risk. FLAG: the cited PMID 35546745 is about RAAS-blocker drug interactions, not butyrate - citation mismatch; the potassium-load mechanism is sound.
Label source:
Class inference
Action type:
avoid
Target id:
/condition/renal-impairment
Target name:
Renal Impairment
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Impaired kidney function reduces the ability to excrete minerals like sodium and potassium, making the salt load from butyrate supplements potentially dangerous.
Actionable advice:
Butyrate supplements, especially sodium or potassium salts, should be avoided with kidney disease.
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: impaired kidneys excrete potassium/sodium less efficiently, so the salt (Na/K) load from butyrate supplements is a plausible concern. FLAG: the cited PMID 35546745 (RAAS blockers) does not address butyrate - citation mismatch; mechanism is sound.
Label source:
Class inference
Action type:
avoid
Target id:
/condition/heart-failure
Target name:
Heart Failure or Hypertension
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Sodium butyrate contains a significant sodium load, which can increase blood pressure and cause fluid retention, worsening these conditions.
Actionable advice:
Sodium butyrate should be avoided with heart failure or hypertension; a calcium/magnesium salt form is preferable if approved by a 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: sodium butyrate carries a sodium load that could, at high doses, contribute to fluid retention/blood-pressure concerns in heart failure; at typical supplement doses the sodium load is modest, so the concern is theoretical. FLAG: the cited PMID 41499750 is an unrelated herbicide paper - citation mismatch.
Label source:
Class inference
Action type:
avoid
Target id:
/class/antibiotics-long-term
Target name:
Antibiotics (Long-term Use)
Severity:
moderate
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Long-term antibiotic use can deplete the gut bacteria that produce butyrate. Supplementation can help replenish this key colonic fuel source and support gut lining integrity.
Actionable advice:
Consider taking butyrate during and after a course of antibiotics to support gut health.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Disruptions to BPB abundance, which is correlated with Western dietary patterns, food additives, and antibiotic exposure, are linked to gut dysbiosis
Label source:
PMID 41683715. Supports antibiotics depleting butyrate-producing bacteria; supplementation as replenishment is the review's therapeutic thesis.
Action type:
informational_none
Target id:
/class/chelating-antibiotics
Target name:
Chelating Antibiotics (Tetracyclines, Quinolones)
Severity:
moderate
Interaction type:
diminishing
Nature:
temporal
Temporal spacing:
Hours before target:
2
Hours after target:
4
Description:
The calcium and magnesium in some butyrate supplements can bind to certain antibiotics in the gut, significantly reducing their absorption and effectiveness.
Actionable advice:
If taking calcium/magnesium butyrate, separate doses from these antibiotics by at least 2 hours before or 4 hours after.
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: IF a butyrate product contains calcium/magnesium salts, those divalent cations can chelate tetracyclines/fluoroquinolones in the gut and reduce their absorption; separate dosing. FLAG: the cited source is an NIH ODS Vitamin D fact sheet, which is the wrong document - the cation-chelation mechanism is well-established but unsupported by that citation.
Label source:
Class inference
Action type:
separate
Target id:
/class/thyroid-hormones
Target name:
Thyroid Hormones
Severity:
moderate
Interaction type:
diminishing
Nature:
temporal
Temporal spacing:
Hours before target:
4
Hours after target:
4
Description:
Calcium and magnesium, found in some forms of butyrate, can interfere with the absorption of thyroid hormone medication, reducing its efficacy.
Actionable advice:
Calcium/magnesium butyrate doses and thyroid medication 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:
Biotin supplementation may interfere with immunoassays for TSH, T4, and T3, resulting in erroneous thyroid hormone test results.
Label source:
Action type:
separate
Target id:
/condition/pregnancy
Target name:
Pregnancy
Severity:
minor
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
The safety of high-dose butyrate supplementation during pregnancy has not been established.
Actionable advice:
Butyrate supplementation is generally best avoided during pregnancy unless specifically recommended by a healthcare provider.
Validation status:
unvalidatable
Evidence tier:
tier_e
Evidence basis:
unvalidatable
Evidence anchors:
Source url:
Scientific literature support not found
Exact phrase from label:
Label source:
No-data precaution: high-dose butyrate-supplement safety in pregnancy is not established.
Action type:
avoid
Target id:
/condition/lactation
Target name:
Breastfeeding (Lactation)
Severity:
minor
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
It is unknown if supplemental butyrate passes into breast milk or what effects it may have on an infant; safety has not been established.
Actionable advice:
Butyrate supplementation is generally best avoided while breastfeeding due to a lack of safety data.
Validation status:
unvalidatable
Evidence tier:
tier_e
Evidence basis:
unvalidatable
Evidence anchors:
Source url:
Scientific literature support not found
Exact phrase from label:
Label source:
No-data precaution: it is unknown whether supplemental butyrate passes into breast milk or its effects on an infant.
Action type:
avoid