Meta Information
ID:b-complex-vitamins
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:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Food enhances the absorption of most B vitamins and can reduce gastrointestinal side effects, particularly the flushing associated with niacin (B3).
Actionable advice:
A B-complex supplement is best taken with a meal.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Most B vitamins are generally safe even at intake levels reached with fortified food or supplements.
Label source:
PubMed: The Permanente journal (2022)
Source url:
Exact phrase from label:
Oral niacin and NAM were associated with a range of AEs including GI upset, liver dysfunction, flushing/vasodilatory effects, skin rash and fatigue.
Label source:
PubMed: Eye (London, England) (2025)
Source url:
Exact phrase from label:
Niacin is a water-soluble B vitamin (B3) known to have favorable effects on multiple lipid parameters, including raising high-density lipoprotein cholesterol (HDL-C) levels and lowering triglycerides (TGs), lipoprotein(a), and low-density lipoprotein cholesterol (LDL-C).
Label source:
PubMed: Postgraduate medicine (2011)
Action type:
informational_none
Target id:
/circadian/wake
Target name:
Morning / Waking Hours
Severity:
minor
Interaction type:
synergistic
Nature:
temporal
Temporal spacing:
Hours before target:
null
Hours after target:
4
Description:
B vitamins are cofactors in energy metabolism; taking them in the morning aligns with the body's natural energy production cycles and may prevent sleep disturbances.
Actionable advice:
It is generally best taken in the morning or early afternoon to support daytime energy levels.
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 timing heuristic: B vitamins are energy-metabolism cofactors, so morning dosing is commonly suggested. Low-evidence practical guidance, not a demonstrated effect. (The cited combined ODS 'BVitamins' sheet does not exist as a single page.)
Label source:
Class inference
Action type:
informational_none
Target id:
/intervention/metformin
Target name:
Metformin
Severity:
major
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Long-term metformin use significantly impairs the absorption of vitamin B12 in the intestines, leading to a high risk of deficiency.
Actionable advice:
If taking metformin long-term, ensure adequate B12 intake and monitor B12 levels regularly.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
(5.1) Vitamin B 12 Deficiency: Metformin may lower vitamin B 12 levels.
Label source:
Action type:
monitor
Target id:
/class/acid-suppressors
Target name:
Acid Suppressors (PPIs, H2 Blockers)
Severity:
moderate
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Chronic use of acid-reducing medications impairs the release of vitamin B12 from food proteins, reducing its absorption over time.
Actionable advice:
If using acid suppressors long-term, monitor vitamin B12 status and consider supplementation.
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: vitamin B12 absorption requires gastric acid to free B12 from food protein, so chronic acid suppression (PPIs/H2 blockers) can lower B12 status over time; effect on supplemental (already-free) B12 is smaller. Monitoring rationale, not a labeled supplement interaction.
Label source:
Class inference
Action type:
monitor
Target id:
/intervention/levodopa
Target name:
Levodopa
Severity:
major
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Vitamin B6 (pyridoxine) accelerates the conversion of levodopa to dopamine in the periphery, preventing it from reaching the brain and reducing its therapeutic effect. This interaction is largely mitigated by co-administration with carbidopa.
Actionable advice:
B-complex supplements containing high-dose B6 should not be used with levodopa without carbidopa; it is important to consult a neurologist.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Higher doses of carbidopa/levodopa may increase the risk of vitamin B6 deficiency.
Label source:
FDA label: Carbidopa-Levodopa (Sinemet)
Action type:
avoid
Target id:
/class/anticonvulsants
Target name:
Anticonvulsant Medications
Severity:
moderate
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Certain anticonvulsants (e.g., phenytoin, carbamazepine, phenobarbital) can lower blood levels of folate (B9), B6, and biotin (B7), while high-dose folate can in turn lower levels of the medication.
Actionable advice:
It is a good idea to consult a doctor about monitoring B vitamin levels and the potential need for supplementation while on long-term anticonvulsant therapy.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Phenytoin may also produce lower than normal values for dexamethasone or metyrapone tests.
Label source:
Action type:
monitor
Target id:
/intervention/methotrexate
Target name:
Methotrexate
Severity:
major
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Methotrexate works by blocking the action of folate (B9); supplementing with folate can interfere with the drug's efficacy for cancer or autoimmune conditions.
Actionable advice:
Folate supplements should be taken only under the strict guidance of the prescribing physician, as folate is sometimes used to manage 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:
Coadministration of methotrexate with folic acid or its derivatives decreases the clinical effectiveness of methotrexate in patients with neoplastic diseases.
Label source:
Methotrexate (methotrexate sodium) FDA label, Sec. 7.1 / 5.10 Folic Acid Supplementation (Neoplastic Diseases).
Action type:
informational_none
Target id:
/biomarker/thyroid-panel
Target name:
Lab Immunoassays (e.g., Thyroid, Troponin)
Severity:
major
Interaction type:
assay_interference
Nature:
temporal
Temporal spacing:
Hours before target:
72
Hours after target:
null
Description:
High levels of supplemental biotin (B7) can interfere with streptavidin-biotin based laboratory tests, causing falsely high or low results for hormones (thyroid, sex hormones), cardiac markers (troponin), and other analytes.
Actionable advice:
Any supplements containing biotin should be stopped for at least 3 days before having blood work done.
Validation status:
validated_via_clinical_guidance
Evidence tier:
tier_b
Evidence basis:
clinical_guidance_verbatim
Evidence anchors:
Exact phrase from label:
Very high intakes of biotin may interfere with diagnostic assays that use biotin-streptavidin technology and are commonly used to measure levels of hormones (such as thyroid hormone) and other analytes such as 25-hydroxyvitamin D, producing falsely normal or abnormal results.
Label source:
NIH ODS Biotin fact sheet, Interactions with Laboratory Tests. FDA has warned of biotin assay interference (including a falsely low troponin linked to a patient death).
Action type:
monitor
Target id:
/biomarker/vitamin-b12
Target name:
Vitamin B12 Deficiency Diagnosis
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
High-dose folate (B9) supplementation can correct the megaloblastic anemia caused by vitamin B12 deficiency, masking the condition while allowing irreversible neurological damage to progress.
Actionable advice:
Vitamin B12 status should be adequate before starting high-dose folate supplementation, and B-complex formulas should be balanced.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
In the 1940s to 1950s, high-dose folic acid supplements (>5 mg/d) were used clinically to reverse the megaloblastic anemia of vitamin B12 deficiency caused by pernicious anemia. However, this treatment strategy masked the underlying B12 deficiency and possibly exacerbated its neuropathological progression.
Label source:
PubMed: Food and nutrition bulletin (2024)
Source url:
Exact phrase from label:
Given the potential dangers of high levels of folate in the general diet, particularly the masking of the hematologic effects of vitamin B-12 deficiency in elderly persons, with the consequent possibility of vitamin B-12 deficiency presenting as severe, irreversible neurologic disease, it is suggested that, until the impact of increasing the general folate level of the diet is better understood, tablet supplementation of folate to women of child-bearing age is preferable as an interim measure to increased food fortification.
Label source:
PubMed: The American journal of clinical nutrition (1994)
Source url:
Exact phrase from label:
Between 1945 and 1959 it was convincingly documented that folic acid can precipitate or aggravate the neurological and haematological consequences of vitamin B12 deficiency by increasing the demand for vitamin B12. Since then there has been much misunderstanding of the issues, mainly by advocates of folic acid fortification who have been inclined to minimise or even dismiss the risks by misinterpreting the evidence as only a 'masking' of the anaemia of pernicious anaemia.
Label source:
PubMed: European journal of clinical nutrition (2016)
Action type:
monitor
Target id:
/condition/alcohol-chronic
Target name:
Chronic Alcohol Use (Alcohol Use Disorder)
Severity:
major
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Chronic alcohol intake impairs the absorption and increases the excretion of multiple B vitamins, especially thiamine (B1), folate (B9), and B6, leading to a high risk of severe deficiency.
Actionable advice:
Heavy alcohol use sharply raises B-vitamin needs (especially thiamine) and risks deficiency. If you drink heavily, supplement B-complex (with extra thiamine) and don't rely on diet alone.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
reduced folate transport activity in renal tissue during chronic ethanol ingestion was attributable to decreased expression of reduced folate carrier (RFC) and folate binding protein (FBP)... which may result in low blood folate levels commonly observed in alcoholics.
Label source:
Wani & Kaur, PMID 18008023. FLAG: rat study, and it directly evidences only the FOLATE limb; the broader thiamine/B6 depletion claim is established clinically but not from this source.
Action type:
avoid
Target id:
/intervention/vitamin-c
Target name:
High-Dose Vitamin C
Severity:
minor
Interaction type:
diminishing
Nature:
temporal
Temporal spacing:
Hours before target:
2
Hours after target:
2
Description:
Theoretically, taking very large doses of vitamin C (over 500mg) at the same time as vitamin B12 could lead to the degradation of B12 in the digestive tract.
Actionable advice:
Doses of B-complex and high-dose vitamin C are best separated by at least 2 hours.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
By employing whole body counter techniques it has been shown that, while ascorbic acid can partially inactivate both the important dietary analogue, hydroxycobalamin, and the gastric secretion, intrinsic factor which is essential for B12 absorption, the rapid binding of the B12 analogue to intrinsic factor protects the hydroxycobalamin from attack.
Label source:
PubMed: Scottish medical journal (1982)
Source url:
Exact phrase from label:
There is also the possibility that vitamin C taken simultaneously with other drugs may contribute to adverse health effects and that its interference in clinical laboratory tests will mask diagnosis of disease.
Label source:
PubMed: Seminars in oncology (1983)
Source url:
Exact phrase from label:
Various nutrients and dietary components interfere with the bioavailability of vitamins. Hence, requirements for vitamins cannot be considered independently, but must be evaluated in relationship to other nutrients and compounds consumed by an individual.
Label source:
PubMed: Progress in food & nutrition science (1985)
Action type:
separate
Target id:
/class/statins
Target name:
Statins
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Combining high-dose niacin (B3) with statin medications increases the risk of myopathy, a condition involving muscle pain and damage.
Actionable advice:
High-dose niacin is best not taken with statins unless specifically prescribed and monitored by a doctor.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Cases of myopathy/rhabdomyolysis have been reported with atorvastatin co-administered
with lipid modifying doses (>1 gram/day) of niacin, fibrates, colchicine, and ledipasvir plus
sofosbuvir [see Adverse Reactions (6.1)].
Label source:
Action type:
avoid
Target id:
/class/loop-diuretics
Target name:
Loop Diuretics (e.g., Furosemide)
Severity:
moderate
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Long-term use of loop diuretics increases the urinary excretion of thiamine (B1), potentially leading to deficiency.
Actionable advice:
Consider thiamine monitoring or supplementation if on long-term loop diuretic therapy.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
12 CLINICAL PHARMACOLOGY 5.3 Ototoxicity
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action 5.4 Acute Urinary Retention 12.2 Pharmacodynamics 5.5 Incomplete Dosing
12.1 Mechanism of Action
Furosemide primarily inhibits the reabsorption of sodium and chloride in the proximal and distal tubules and in the loop of Henle.
Label source:
Action type:
monitor
Target id:
/class/bile-acid-sequestrants
Target name:
Bile Acid Sequestrants
Severity:
moderate
Interaction type:
diminishing
Nature:
temporal
Temporal spacing:
Hours before target:
4
Hours after target:
1
Description:
Medications like cholestyramine can bind to niacin (B3) and folate (B9) in the gut, reducing their absorption.
Actionable advice:
B-complex is best taken at least 1 hour before or 4-6 hours after a bile acid sequestrant.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Because cholestyramine binds bile acids, QUESTRAN may interfere with normal fat digestion
and absorption and thus may prevent absorption of fat-soluble vitamins such as A, D, E and
K.
Label source:
Action type:
separate
Target id:
/condition/peripheral-neuropathy
Target name:
Peripheral Neuropathy
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Chronic intake of high doses of vitamin B6 (pyridoxine), typically above 100 mg per day, can cause or worsen sensory peripheral neuropathy, a type of nerve damage.
Actionable advice:
Long-term daily intake of vitamin B6 in excess of 100 mg should be avoided 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:
vitamin B6 hypervitaminosis is neurotoxic and may provoke a progressive sensory neuronopathy (sensory ganglionopathy), usually when daily uptake is above 50 mg.
Label source:
Echaniz-Laguna et al., BMJ Case Rep (2018), PMID 29954767. Supports chronic high-dose B6 causing sensory neuropathy (the basis for the 100 mg/day UL).
Action type:
avoid
Target id:
/intervention/tetracycline-antibiotics
Target name:
Tetracycline Antibiotics
Severity:
moderate
Interaction type:
diminishing
Nature:
temporal
Temporal spacing:
Hours before target:
2
Hours after target:
2
Description:
B vitamins can interfere with the absorption and effectiveness of tetracycline antibiotics. This is less of a concern with doxycycline and minocycline.
Actionable advice:
Doses of B-complex and tetracycline antibiotics should be separated by at least 2 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: tetracyclines chelate polyvalent cations - if the B-complex product also contains minerals (iron, calcium, magnesium, zinc) these can bind tetracycline and reduce its absorption; separate dosing by 2-3 h. The B-vitamins themselves are not the interacting moiety. Practical caution.
Label source:
Class inference
Action type:
separate