Meta Information
ID:vitamin-b6
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:
/intervention/vitamin-b6
Target name:
High-Dose Long-Term Use
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Chronic intake of high-dose Vitamin B6 (pyridoxine), typically above 100 mg per day, can be neurotoxic and lead to progressive sensory neuropathy, causing symptoms like numbness and tingling in the hands and feet.
Actionable advice:
The Tolerable Upper Intake Level of 100 mg/day for adults should not be exceeded unless specifically directed by a healthcare provider.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
We describe seven adults who had ataxia and severe sensory-nervous-system dysfunction after daily high-level pyridoxine (vitamin B6) consumption.
Label source:
PubMed: Sensory neuropathy from pyridoxine abuse. A new megavitamin syndrome. (PMID 6308447)
Action type:
informational_none
Target id:
/intervention/levodopa
Target name:
Levodopa (without Carbidopa)
Severity:
major
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Vitamin B6 is a cofactor for an enzyme that breaks down levodopa in the bloodstream before it can reach the brain, severely reducing its effectiveness for treating Parkinson's disease.
Actionable advice:
All Vitamin B6 supplements should be avoided when taking levodopa alone. This interaction is prevented by carbidopa, a component in most modern levodopa prescriptions (e.g., Sinemet).
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Aromatic-L-aminoacid (dopa) decarboxylase (ALAAD) was determined in human plasma by its ability to form dopamine from the substrate 3,4-dihydroxyphenylalanine in the presence of pyridoxal-5-phosphate as cofactor.
Label source:
PubMed: Determination of aromatic-L-amino acid decarboxylase in human plasma. (PMID 3769207)
Action type:
avoid
Target id:
/intervention/magnesium
Target name:
Magnesium
Severity:
moderate
Interaction type:
synergistic
Nature:
temporal
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Magnesium is an essential cofactor for the kinase enzyme that converts Vitamin B6 into its biologically active form, pyridoxal-5'-phosphate (P5P), within the body.
Actionable advice:
Vitamin B6 and Magnesium are best taken at the same time to ensure optimal activation and utilization of the vitamin.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
AC-EAST was significantly increased on day 70, implying that the animals were at risk for vitamin B6 deficiency. CONCLUSION: Mg deficiency impairs vitamin B6 status by depleting intracellular Mg and thus inhibits the activity of alkaline phosphatase, a metalloenzyme required for the uptake of pyridoxal phosphate by tissues.
Label source:
PubMed: Journal of the American College of Nutrition (1997)
Source url:
Exact phrase from label:
Pyridoxal kinase is a ubiquitous enzyme essential for pyridoxal 5'-phosphate (PLP) homeostasis since PLP is required for the catalytic activity of a variety of PLP-dependent enzymes involved in amino acid, lipid, and sugar metabolism as well as neurotransmitter biosynthesis.
Label source:
PubMed: Biochemical and biophysical research communications (2016)
Source url:
Exact phrase from label:
This system harnesses inexpensive sodium hexametaphosphate (SHMP) as a phosphoryl donor to drive continuous ATP regeneration, thereby enabling efficient phosphorylation of pyridoxal to PLP without exogenous ATP input.
Label source:
PubMed: Bioorganic chemistry (2026)
Action type:
informational_none
Target id:
/class/vitamin-b6-depleting-drugs
Target name:
Drugs that Deplete Vitamin B6 (e.g., Isoniazid, Hydralazine, Penicillamine, Theophylline, Oral Contraceptives)
Severity:
moderate
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Certain medications can act as Vitamin B6 antagonists, interfere with its metabolism, or increase its excretion, leading to a deficiency that supplementation can correct.
Actionable advice:
If taking these medications long-term, discuss with your doctor whether Vitamin B6 supplementation is necessary to prevent deficiency.
Validation status:
validated_via_expert_review
Evidence tier:
tier_c
Evidence basis:
expert_review_verbatim
Evidence anchors:
Exact phrase from label:
Theoretically, antibiotics might reduce levels of vitamin B6
Label source:
NatMed Professional Monograph: Vitamin B6 (Pyridoxine)
Action type:
informational_none
Target id:
/condition/renal-impairment
Target name:
Renal Impairment / Dialysis
Severity:
moderate
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Kidney disease impairs the conversion of Vitamin B6 to its active form and increases its loss from the body, often necessitating supplementation to prevent deficiency and related complications like high homocysteine.
Actionable advice:
If you have kidney disease, consult your nephrologist about appropriate Vitamin B6 dosing.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
In the majority of patients with chronic renal failure and in patients during various forms of renal replacement therapy can develop vitamin B6 deficiency from many causes.
Label source:
PubMed: Kidney international. Supplement (1997)
Source url:
Exact phrase from label:
We found vitamin B6 deficiency and high tHcy (fasting and PML) levels in all patients. Plasma and RBC levels of pyridoxal and pyridoxal phosphate were abnormally low, whereas levels of pyridoxic acid (PA), an end product of vitamin B6 metabolism, were extremely high in both groups.
Label source:
PubMed: American journal of kidney diseases : the official journal of the National Kidney Foundation (2002)
Source url:
Exact phrase from label:
Amongst the various causes of malnutrition in DKD, the metabolic mechanisms of vitamin B (B1 (Thiamine), B2 (Riboflavin), B3 (Niacin/Nicotinamide), B5 (Pantothenic Acid), B6 (Pyridoxine), B8 (Biotin), B9 (Folate), and B12 (Cobalamin)) deficiency and its clinical impact has garnered greater scientific interest over the past decade.
Label source:
PubMed: Biomedicines (2023)
Action type:
informational_none
Target id:
/biomarker/homocysteine
Target name:
Elevated Homocysteine Levels
Severity:
moderate
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Vitamin B6, as its active form P5P, is a critical cofactor for two key enzymes (cystathionine β-synthase and cystathionine γ-lyase) in the transsulfuration pathway that metabolizes and clears homocysteine.
Actionable advice:
If you have high homocysteine, ensure adequate intake of B6, B12, and folate as part of a comprehensive management plan.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
We saw similar inverse associations between homocysteine and intakes of folate and vitamin B6, but not vitamin B12.
Label source:
PubMed: Relationship between plasma homocysteine and vitamin status in the Framingham study population. Impact of folic acid fortification. (PMID 11411265)
Action type:
monitor
Target id:
/condition/alcohol-chronic
Target name:
Chronic Alcohol Use (Alcohol Use Disorder)
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Chronic heavy alcohol intake produces acetaldehyde, which displaces the active form of B6 (P5P) from its binding proteins, making it susceptible to breakdown and leading to a functional deficiency.
Actionable advice:
Heavy alcohol consumption is best avoided; for those who drink regularly, it is a good idea to discuss B6 status and potential need for supplementation with a healthcare provider.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Inasmuch as acetaldehyde has no effect on the synthesis of pyridoxal phosphate, it has also been postulated that acetaldehyde accelerates pyridoxal phosphate degradation by displacing this coenzyme from binding proteins, which protect it against hydrolysis.
Label source:
PubMed: The Journal of clinical investigation (1978)
Source url:
Exact phrase from label:
Acetaldehyde increases the degradation of pyridoxal 5'-phosphate by displacing it from its binding protein and making it susceptible to hydrolysis by membrane-bound alkaline phosphatase.
Label source:
PubMed: Federation proceedings (1985)
Source url:
Exact phrase from label:
These data support previous findings whic indicate that acetaldehyde is the responsible agent which acts by accelerating the degradation of intracellular pyridoxal phosphate.
Label source:
PubMed: The Journal of clinical investigation (1975)
Action type:
avoid
Target id:
/class/chemotherapy-radiation
Target name:
Certain Chemotherapy Drugs
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Vitamin B6 may interact with the mechanisms of certain chemotherapy agents (e.g., 5-Fluorouracil, Doxorubicin), potentially altering their effectiveness or side effect profile.
Actionable advice:
It is important to consult an oncologist before taking any supplements, including Vitamin B6, during cancer treatment.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
The 400 mg pyridoxine group had, however, a worsened tumor response and tended to have greater tumor treatment failure and shorter time to treatment failure.
Label source:
PubMed: Randomized trial of two different doses of pyridoxine in the prevention of capecitabine-associated palmar-plantar erythrodysesthesia. (PMID 20887495)
Action type:
informational_none
Target id:
/intervention/b-complex
Target name:
B-Complex Vitamins (especially B2, B9, B12)
Severity:
minor
Interaction type:
synergistic
Nature:
temporal
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Vitamin B6 requires Vitamin B2 (riboflavin) for its conversion to the active P5P form, and it works in concert with folate (B9) and B12 in single-carbon metabolism pathways like homocysteine regulation.
Actionable advice:
Vitamin B6 is generally best taken as part of a B-complex or alongside other B vitamins for optimal function.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
B vitamins may alter depressive symptoms by many various mechanisms such as reducing oxidative stress, inflammation, gut permeability, controlling epigenetics, modifying the microbiome, and stimulating it to produce many beneficial substances such as short-chain fatty acids or neurotransmitters: norepinephrine, dopamine, serotonin, gamma-aminobutyric acid, and acetylcholine. Specifically, vitamins B1 (thiamine), B6 (pyridoxine), B9 (folate), and B12 (cyanocobalamin), B2 (riboflavin) have been observed to affect depression.
Label source:
PubMed: Circulating B vitamins metabolites in depressive disorders - connections with the microbiota-gut-brain axis. (PMID 38992845)
Action type:
informational_none
Target id:
/intervention/zinc
Target name:
Zinc
Severity:
minor
Interaction type:
synergistic
Nature:
temporal
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Zinc is a necessary cofactor for the enzyme alkaline phosphatase, which is involved in the metabolism of Vitamin B6's active form, P5P.
Actionable advice:
Consider taking Zinc and Vitamin B6 together, as they are often co-factors in metabolic processes.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
It is generally believed that the zinc metalloenzyme alkaline phosphatase is required to hydrolyze phosphorylated forms of vitamin B-6 prior to their use.
Label source:
PubMed: Biological trace element research (1993)
Source url:
Exact phrase from label:
The data strongly favor alkaline phosphatase as the enzyme which functions in the control of pyridoxal-P and pyridoxamine-P metabolism in rat liver.
Label source:
PubMed: The Journal of biological chemistry (1975)
Source url:
Exact phrase from label:
Pyridoxal kinase, a key enzyme in the formation of vitamin B6 coenzymes, requires a zinc-ATP complex as a substrate.
Label source:
PubMed: Nutrition reviews (1990)
Action type:
informational_none
Target id:
/dietary/meal
Target name:
Any Caloric Meal
Severity:
minor
Interaction type:
informational
Nature:
temporal
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Taking Vitamin B6 with food can improve tolerance and prevent potential mild nausea, although it is a water-soluble vitamin that is well-absorbed on an empty stomach.
Actionable advice:
It is generally best taken with a meal to minimize any potential for stomach upset.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Significantly larger lag times after administration of both formulations were observed under post-meal conditions than under pre-meal conditions (0.477 +/- 0.315 h versus 0.081 +/- 0.086 h for PC and 1.995 +/- 1.345 h versus 1.064 +/- 1.327 h for EC), indicating that the mean gastric emptying rates of both a solution and a tablet were delayed after food intake.
Label source:
PubMed: Biopharmaceutics & drug disposition (1994)
Source url:
Exact phrase from label:
Unlike the lipophilic vitamins A, D, and E, water-soluble vitamin B6 is well tolerated at high doses.
Label source:
PubMed: mBio (2014)
Source url:
Exact phrase from label:
Using the adjusted numbers for actual water vitamin concentration, there were no differences in the maximum concentration and the 5-h area under the curve for vitamins B(6), B(12) or C between the VW and the MM.
Label source:
PubMed: International journal of food sciences and nutrition (2009)
Action type:
informational_none
Target id:
/circadian/sleep
Target name:
Going to Sleep
Severity:
minor
Interaction type:
adverse
Nature:
temporal
Temporal spacing:
Hours before target:
3
Hours after target:
null
Description:
Vitamin B6 is involved in the synthesis of stimulating and calming neurotransmitters; in some individuals, taking it near bedtime can lead to unusually vivid dreams or sleep disturbances.
Actionable advice:
Vitamin B6 is generally best taken in the morning or early afternoon to avoid any potential interference with sleep quality.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
PLP-dependent enzymes for which there are already commercially available drugs are DOPA decarboxylase (involved in the Parkinson disease), GABA aminotransferase (epilepsy), serine hydroxymethyltransferase (tumors and malaria), ornithine decarboxylase (African sleeping sickness and, potentially, tumors), alanine racemase (antibacterial agents), and human cytosolic branched-chain aminotransferase (pathological states associated to the GABA/glutamate equilibrium concentrations).
Label source:
PubMed: Pyridoxal 5'-phosphate enzymes as targets for therapeutic agents. (PMID 17504214)
Action type:
avoid
Target id:
/intervention/amiodarone
Target name:
Amiodarone
Severity:
minor
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Both the antiarrhythmic drug amiodarone and high doses of Vitamin B6 can independently cause photosensitivity, and taking them together may have an additive effect, increasing the risk of severe sunburn.
Actionable advice:
Enhanced sun protection (high-SPF sunscreen, protective clothing) may help if high-dose Vitamin B6 is taken with amiodarone.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
All ten patients we have treated so far with amiodarone for cardiac arrhythmias have shown a similar photosensitivity, indicating that this is probably a phototoxic reaction.
Label source:
PubMed: Archives of dermatology (1984)
Source url:
Exact phrase from label:
Phototoxic reactions occur when the skin is exposed to sunlight after administering topical or systemic medications that exhibit photosensitizing activity.
Label source:
PubMed: Journal of photochemistry and photobiology (2024)
Source url:
Exact phrase from label:
Amiodarone has a number of serious adverse effects, including corneal microdeposits (>90%), optic neuropathy/neuritis (< or =1%-2%), blue-gray skin discoloration (4%-9%), photosensitivity (25%-75%), hypothyroidism (6%), hyperthyroidism (0.9%-2%), pulmonary toxicity (1%-17%), peripheral neuropathy (0.3% annually), and hepatotoxicity (elevated enzyme levels, 15%-30%; hepatitis and cirrhosis, <3% [0.6% annually]).
Label source:
PubMed: JAMA (2007)
Action type:
informational_none