Vitamin B6 Deficiency (Pyridoxine)


Article Author:
Mary Brown


Article Editor:
Kevin Beier


Editors In Chief:
Laura Stanley
Diana Peterson
Chantal Prewitt


Managing Editors:
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Frank Smeeks
Kristina Soman-Faulkner
Benjamin Eovaldi
Radia Jamil
Sobhan Daneshfar
Saad Nazir
William Gossman
Pritesh Sheth
Hassam Zulfiqar
Navid Mahabadi
Steve Bhimji
John Shell
Matthew Varacallo
Ahmad Malik
Mark Pellegrini
James Hughes
Beata Beatty
Hajira Basit
Phillip Hynes


Updated:
1/26/2019 9:53:02 PM

Introduction

Water-soluble vitamin B6 is widely present in many foods, including meat, fish, nuts, beans, grains, fruits and vegetables. Additionally, B6 is present in many multivitamin preparations for adults and children and added to foods as a supplement to breakfast foods, power bars, and powders.

There are several active compounds or vitamers which fall under the generic B6. These include (1) pyridoxine an alcohol, (2) pyridoxal an aldehyde, (3) pyridoxamine which differs from the first two with an amine group, and (4) a 2,5' phosphate esters. The major esters are the active coenzyme form and are pyridoxal 5'phosphate(PLP) and pyridoxamine 5'phosphate(PMP). The major form of B6 in meats are the esters, and the major plant source is pyridoxine, which is less bioavailable. Pyridoxine is the most common form found in multivitamins. 

As a coenzyme, B6 is involved as a cofactor in over 100 enzyme reactions including amino acid metabolism, particularly homocysteine; carbohydrate metabolism, including gluconeogenesis and glycogenolysis; and lipid metabolism. B6 has a role in cognitive development thru neurotransmitter synthesis, immune function with interleukin-2 production, and hemoglobin formation.

Fetal brain development requires adequate B6, and this continues throughout infancy. Vitamin B6 recommendations are made in accordance with age and life stage with pregnancy and breastfeeding involving the highest recommended daily allowance.[1][2][3][4]

Etiology

In the United States and other western cultures, deficiency is rare with adequate diets, including B6 sources from poultry, fish, organ meats, potatoes, grains, legumes and noncitrus fruits.

Vitamin B6 deficiency is rare in isolation and usually found in association with other B vitamin deficiencies such as folic acid and B12. 

Low plasma levels of active B6 are found in chronic alcohol dependence, with obese states, pregnancy, preeclampsia and eclampsia, and malabsorptive states such as celiac, inflammatory bowel disease, and bariatric surgery.

Additional at-risk groups with inadequate intake or increased metabolic requirements may become functionally deficient in B6.  Included in this group are those with renal impairment, autoimmune disorders, and chronic alcohol use. Patients with chronic renal failure, especially those receiving hemodialysis or peritoneal dialysis, have low plasma levels of B6. Autoimmune disorders, such as rheumatoid arthritis, have increased catabolism of B6, resulting in higher demand for dietary supplementation of B6.

Of great clinical importance in toxicology is that drug antagonists to vitamin B6 occurs with the tuberculosis medicine isoniazid. Also, penicillamine and levodopa, as well as some anticonvulsant medications, may interfere with B6 metabolism.[5][6][7][8]

Epidemiology

Risk factors for altered B6 may include excessive or inadequate ingestion. Specifics causes of B6 deficiency have been attributed to inadequate gastrointestinal (GI) absorption, hepatic dysfunction, and drug interaction or antagonism.

The human body cannot store B6, and thus a daily source is required. There appears to be a bioavailability preference for meat over plant source B6. This may be important to those who favor a plant-based diet exclusively. These individuals may need added supplementation. The major supplement in multivitamins is a pyridoxine hydrochloride. Dietary intake and the bioavailability of ingested B6 may vary, as well as the urinary excretion.

RDA or recommended dietary allowance for  B6 in adults is 1 to 1.7mg per day. Children ages 1 to 3 are recommended to have 0.5 mg per day, and those 3 to 13 are recommended to have 1 mg per day. During pregnancy and lactation, the recommendations are 1.9 mg and 2 mg per day.

The average diet for adults is estimated to include 6 to 10 mg of Pyridoxine vitamers. Excessive amounts exceed 250 mg per day and, on a chronic basis, may result in toxicity leading to untoward effects on skin, GI, and the neurologic system.

Pathophysiology

Vitamin B6 is predominantly absorbed in the small intestine jejunum and is metabolized at the cellular level in the mitochondria and cytosol to active forms in the liver. Excretion of excess B6 occurs in the kidney and is albumin-bound in plasma.  The half-life elimination exceeds 15 to 20 days.

Vitamin B6 deficiency may present with seizures in the young.  Severely deficient adults commonly present with rashes and mental status changes. Additional clinical findings of deficiency may include normocytic anemia, a nonspecific pruritic rash, cheilitis with scaly lip skin and cracks in the corner of the mouth and glossitis (swelling of the tongue). Depression is associated with a severe B6 deficiency as well.

Current studies are evaluating the role of B6 deficiency in heart disease, cancer, and cognitive decline as medical conditions that may respond to supplementation. To date, there is no clear evidence to support supplement use beyond the normal dietary intake.  However, some studies indicate a reduction of symptoms in the premenstrual syndrome with supplementation of B6, particularly a decrease in moodiness, irritability, and forgetfulness. The American College of Obstetrics and Gynecology recommend vitamin B6 supplementation (1.9 mg per day) for hyperemesis gravidarum.[9]

Toxicokinetics

Vitamin B6 is water soluble. B6 is one of three water-soluble vitamins that can have toxicity at excessive doses; the others being Niacin (Vitamin B2) and Ascorbic acid (Vitamin C).

It is rare to develop B6 toxicity for an individual on ordinary food diets without supplementation. Excessive supplementation for chronic periods (months to greater than a year) has resulted in sensory neuropathies and movement disorders. The severity of symptoms is dose-dependent. Additional clinical findings of toxicity may include photosensitivity, GI symptoms such as nausea and heartburn, as well as painful dermatological eruptions. These symptoms resolve for the most part over time with the elimination of the B6 supplement. The B6 toxicity-induced sensory polyneuropathy causes decreased touch, temperature, and vibration sensation and results in poor coordination.  

In toxicology, Vitamin B6 is clinically important in the treatment of Isoniazid (INH), ethylene glycol, and Gyromitrin (toxic mushroom) poisoning.  Additionally, it is used preventatively during isoniazid (INH) therapy of tuberculosis to prevent INH-induced polyneuropathy.

History and Physical

History should be targeted, and age focused. In the neonate with seizures, mothers with poor nutritional status may be suggestive of a vitamin B6 deficiency.  Also, consideration should be given to inborn error of metabolism that is Vitamin B6-dependent.

The older patient should be questioned on nutritional intake, supplement use, and medication history. Also critically important is eliciting a history of potential malabsorption syndromes which have been strongly associated with Vitamin B6 deficiency such as inflammatory bowel disease, celiac, or surgery of the small intestines including bariatric surgery. On a review of systems, the finding of weakness, mental status change, paresthesias, or other sensory or dermatological symptoms may suggest the diagnosis.

Physical exam findings may include confusion and skin lesions, particularly facial lesions such as stomatitis, glossitis, seborrheic dermatitis, and angular cheilitis. Objective physical findings may include peripheral neuropathies, skin photosensitivity, and movement disorders.

Evaluation

Early or subclinical vitamin B6 deficiency may have vague or fleeting symptoms; however, new onset sensory polyneuropathy, altered mental status, dermatitis in adults, or seizures in infancy should raise clinical suspicion of a clinically significant B6 deficiency. Testing for vitamin B6 can be difficult in real time in many clinical scenarios. Direct serum measurement of the active vitamin Pyridoxal 5′-phosphate (PLP) form is available in some clinical settings, however, the assay is not widely available or timely.  A clinical alternative is an indirect measurement technique of vitamin B6, which includes measuring urinary excretion of xanthurenic acid (an amino acid catabolite of tryptophan) following a measured bolus of tryptophan. Increased levels of xanthurenic acid may indicate inadequate active B6 for the formation of the amino acid tryptophan.

Treatment / Management

In vitamin B6-deficient states and illnesses, treatment dosage is variable and depends on the severity of symptoms. The vitamin is available therapeutically in both oral and parenteral formulations. Neonates with B6 deficiency seizures may require 10 to 100 mg intravenous (IV) for effective treatment of active seizures. Less serious or less acute presentations can be supplemented with doses ranging from 25 mg to 600 mg per day orally depending on symptom complex.

Importantly, Vitamin B6 therapy can be life-saving in refractory INH overdose-induced seizures. The dose is equal to the known amount of INH ingested or a maximum of 5 gms and is dosed 1 to 4 grams IV as the first dose, then 1 g IM or IV every 30 minutes. In ethylene glycol overdose, vitamin B6 is recommended at 50 to 100 mg IV every 6 hours to facilitate shunting the metabolism of ethylene glycol to nontoxic pathways leading to glycine (nontoxic) instead of toxic pathways leading to toxic metabolites such as formate.

Additional, less common uses are in hydralazine overdose where the recommended dose of vitamin B6 is 25 mg/kg, the first third administered intramuscularly and the remainder as a 3-hour IV infusion. Gyromitra (mushroom) toxicity treatment is at 25 mg/kg infused IV over 30 min.

Hyperemesis gravidarum may respond to vitamin B6 at a dosage of 25 mg orally every 8 hours.

Differential Diagnosis

The differential is wide due to the multitude of symptoms and clinical findings associated with B6 deficiency. Some specific disease states with similar symptoms include porphyria, beriberi (thiamine deficiency), normocytic anemias, depression, and the various disorders associated with cognitive decline, folic acid deficiency, INH toxicity, and neonatal seizures.

Prognosis

If diagnosed appropriately, the deficiency is effectively treated with adequate oral or parenteral supplementation.

Pearls and Other Issues

Pyridoxine is the emergency antidote for isoniazid (INH) overdose, ethylene glycol, hydralazine, and gyromitrin mushroom poisoning.  The two most common uses of vitamin B6 are in the treatment of the toxicological emergencies: INH and ethylene glycol overdoses. In INH overdose-related seizure, the dose is 5 grams in adults and 1 gram in children unless the amount of INH is specifically known. Pyridoxine can be given at a rate of 0.5 to 1 gram/minute until seizures stop or maximum dose given. Patients who are asymptomatic and have not had seizures after a potentially toxic ingestion of isoniazid within 2 hours, should receive the recommended dose of pyridoxine. In ethylene glycol overdose, vitamin B6 is recommended at 50 to 100 mg IV every 6 hours to facilitate shunting the metabolism of ethylene glycol to nontoxic pathways leading to glycine (nontoxic) instead of toxic pathways leading to toxic metabolites such as formate.

Enhancing Healthcare Team Outcomes

Healthcare workers should encourage healthy nutrition in all their patients. However, some groups may be at risk for B6 deficiency. These includes patients with renal impairment, autoimmune disorders, and chronic alcohol use. Patients with chronic renal failure, especially those receiving hemodialysis or peritoneal dialysis, have low plasma levels of B6. Autoimmune disorders, such as rheumatoid arthritis, have increased catabolism of B6, resulting in higher demand for dietary supplementation of B6. 

In addition, emergency department physicians should be aware that pyridoxine is the emergency antidote for isoniazid (INH) overdose, ethylene glycol, hydralazine, and gyromitrin mushroom poisoning.  The two most common uses of vitamin B6 are in the treatment of the toxicological emergencies: INH and ethylene glycol overdoses.

Of great clinical importance in toxicology is that drug antagonists to vitamin B6 occurs with the tuberculosis medicine isoniazid. Also, penicillamine and levodopa, as well as some anticonvulsant medications, may interfere with B6 metabolism.

The outcomes for patients with B6 deficiency are good if supplementation is undertaken before severe deficits have developed. (Level V)


Interested in Participating?

We are looking for contributors to author, edit, and peer review our vast library of review articles and multiple choice questions. In as little as 2-3 hours you can make a significant contribution to your specialty. In return for a small amount of your time, you will receive free access to all content and you will be published as an author or editor in eBooks, apps, online CME/CE activities, and an online Learning Management System for students, teachers, and program directors that allows access to review materials in over 500 specialties.

Improve Content - Become an Author or Editor

This is an academic project designed to provide inexpensive peer-reviewed Apps, eBooks, and very soon an online CME/CE system to help students identify weaknesses and improve knowledge. We would like you to consider being an author or editor. Please click here to learn more. Thank you for you for your interest, the StatPearls Publishing Editorial Team.

Vitamin B6 Deficiency (Pyridoxine) - Questions

Take a quiz of the questions on this article.

Take Quiz
A vegetarian is being treated for tuberculosis and later complains of a tingling, pins and needles sensation in his legs. What is the most appropriate therapy for this condition?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Vitamin B6 deficiency is rare and may coincide with deficiency of which other vitamin?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 32-year-old male has immigrated recently from India and presents to the emergency department actively seizing. His wife reports they are having difficulties adjusting and they have argued the last 3 evenings. His medications are over the counter antihistamines, and something she thought was for tuberculosis prevention he has been taking for 3 months. What is the next step in treatment?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which vitamin can improve the oral lesions, cheilitis, and glossitis may improve on anticonvulsants?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 7-day old male infant presents to the emergency department via ambulance with a seizure that initially responded to intravenous lorazepam. Shortly after arrival, the patient developed status epilepticus that was unresponsive to any antiepileptics administered in the emergency department. The infant's bedside blood sugar was 110. He was afebrile and had no evidence of trauma on exam. Which diagnosis should the clinician treating the patient consider and treat most urgently to abort the status seizure in the management of this infant?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Toxicity from which of the following is treated with vitamin B6?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up

Vitamin B6 Deficiency (Pyridoxine) - References

References

Wilson MP,Plecko B,Mills PB,Clayton PT, Disorders Affecting Vitamin B{sub}6{/sub} metabolism. Journal of inherited metabolic disease. 2019 Jan 22;     [PubMed]
Johnstone DL,Al-Shekaili HH,Tarailo-Graovac M,Wolf NI,Ivy AS,Demarest S,Roussel Y,Ciapaite J,van Roermund CWT,Kernohan KD,Kosuta C,Ban K,Ito Y,McBride S,Al-Thihli K,Abdelrahim RA,Koul R,Al Futaisi A,Haaxma CA,Olson H,Sigurdardottir LY,Arnold GL,Gerkes EH,Boon M,Heiner-Fokkema MR,Noble S,Bosma M,Jans J,Koolen DA,Kamsteeg EJ,Drögemöller B,Ross CJ,Majewski J,Cho MT,Begtrup A,Wasserman WW,Bui T,Brimble E,Violante S,Houten SM,Wevers RA,van Faassen M,Kema IP,Lepage N,Lines MA,Dyment DA,Wanders RJA,Verhoeven-Duif N,Ekker M,Boycott KM,Friedman JM,Pena IA,van Karnebeek CDM, PLPHP deficiency: clinical, genetic, biochemical, and mechanistic insights. Brain : a journal of neurology. 2019 Jan 21;     [PubMed]
Badrinath M,John S, Isoniazid Toxicity 2018 Jan;     [PubMed]
Altun H,Şahin N,Belge Kurutaş E,Güngör O, Homocysteine, Pyridoxine, Folate and Vitamin B12 Levels in Children with Attention Deficit Hyperactivity Disorder. Psychiatria Danubina. 2018 Sep;     [PubMed]
Joyce T,Brown FC,Adalat S,Reid CJD,Sinha MD, Vitamin B6 blood concentrations in paediatric dialysis patients. Pediatric nephrology (Berlin, Germany). 2018 Nov;     [PubMed]
Echaniz-Laguna A,Mourot-Cottet R,Noel E,Chanson JB, Regressive pyridoxine-induced sensory neuronopathy in a patient with homocystinuria. BMJ case reports. 2018 Jun 28;     [PubMed]
Strobbe S,Van Der Straeten D, Toward Eradication of B-Vitamin Deficiencies: Considerations for Crop Biofortification. Frontiers in plant science. 2018;     [PubMed]
Banihani SA, A Systematic Review Evaluating the Effect of Vitamin B6 on Semen Quality. Urology journal. 2017 Dec 30;     [PubMed]
Rollón N,Fernández-Jiménez MC,Moreno-Carralero MI,Murga-Fernández MJ,Morán-Jiménez MJ, Microcytic anemia in a pregnant woman: beyond iron deficiency. International journal of hematology. 2015 May;     [PubMed]

Disclaimer

The intent of StatPearls is to provide practice questions and explanations to assist you in identifying and resolving knowledge deficits. These questions and explanations are not intended to be a source of the knowledge base of all of medicine, nor is it intended to be a board or certification review of Neuroscience-Medical Student. The authors or editors do not warrant the information is complete or accurate. The reader is encouraged to verify each answer and explanation in several references. All drug indications and dosages should be verified before administration.

StatPearls offers the most comprehensive database of free multiple-choice questions with explanations and short review chapters ever developed. This system helps physicians, medical students, dentists, nurses, pharmacists, and allied health professionals identify education deficits and learn new concepts. StatPearls is not a board or certification review system for Neuroscience-Medical Student, it is a learning system that you can use to help improve your knowledge base of medicine for life-long learning. StatPearls will help you identify your weaknesses so that when you are ready to study for a board or certification exam in Neuroscience-Medical Student, you will already be prepared.

Our content is updated continuously through a multi-step peer review process that will help you be prepared and review for a thorough knowledge of Neuroscience-Medical Student. When it is time for the Neuroscience-Medical Student board and certification exam, you will already be ready. Besides online study quizzes, we also publish our peer-reviewed content in eBooks and mobile Apps. We also offer inexpensive CME/CE, so our content can be used to attain education credits while you study Neuroscience-Medical Student.