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Vitamin B6 Deficiency

Pyridoxine Deficiency

Vitamin B6 or pyridoxine is a water-soluble vitamin, essential for neural, endocrine, and immune processes, that serves as a cofactor in a number of metabolic processes. A deficiency of vitamin B6 causes neurological impairment.


Presentation

Pyridoxine deficiency causes a wide range of symptoms, all due to derangements in pyridoxine-requiring metabolic processes.

Clinical features of vitamin B6 deficiency include peripheral neuropathy presenting as numbness, weakness, and dysesthesias in the limbs, glossitis, cheilitis, pellagra-like symptoms including seborrheic dermatitis and diarrhea, conjunctivitis, sideroblastic anemia, and neurological symptoms such as confusion, depression, insomnia, irritability, chronic fatigue, EEG abnormalities and convulsions, which are often tonic-clonic seizures.

Peripheral neuropathy presents as numbness, burning or tingling sensations in the feet which ascend to the legs and upper extremities. There is also a loss of sensation and reduced deep tendon reflexes in the lower limbs. Other neurological findings in vitamin B6 deficiency include areflexia and ataxia. In infants, there may be restlessness and irritability.

Studies have revealed an association between vitamin B6 deficiency and a high risk of rheumatoid arthritis and cardiac disease. Other studies have also shown a strong link between vitamin B6 deficiency and Alzheimer's disease, as well as other forms of dementia.

Malnutrition
  • Malnutrition and risk of malnutrition were present in 11.5% and 61% respectively. Dietary intake of B6 (mg/day) in men and women were 1.60 (0.30) and 1.18 (0.31) (recommended 1.6 and 1.2 respectively), and 14 (23%) used B6 supplements.[ncbi.nlm.nih.gov]
  • The nutritional state was unsatisfactory, malnutrition was present in 11.5% and only 27% were at no risk of malnutrition.[bmcgeriatr.biomedcentral.com]
  • Vitamin B6 deficiency can also occur in severe malnutrition, such as many alcoholics experience, and when babies are born to mothers who suffer severe malnutrition from any cause. 2. Many health conditions can cause vitamin B6 deficiency.[healthifybody.com]
  • […] inflammatory disorders and with concurrent use of several medications. [ 6 , 7] Inherited pyridoxine-dependent seizure is a rare autosomal-recessive condition. [ 8 , 9, 10 , 11] Pyridoxine-responsive sideroblastic anemia is also rare. [ 12 ] International Malnutrition[emedicine.medscape.com]
Burning Feet
  • feet syndrome E53.9 Deficiency, deficient vitamin (multiple) E56.9 ICD-10-CM Diagnosis Code E56.9 Vitamin deficiency, unspecified 2016 2017 2018 2019 Billable/Specific Code B (complex) E53.9 group B E53.9 Encephalopathy (acute) G93.40 ICD-10-CM Diagnosis[icd10data.com]
  • Associated with "burning feet" and impaired wound healing.[labtestsonline.org]
Camping
  • There are no new cases of NS reported by Ugandan MOH and WHO since 2012 when the IDP camps were disbanded and communities resettled in their own communities and feed on their own grown foods. Perhaps NS may be akin to Autism Spectrum Disorder (ASD).[unboundmedicine.com]
Intertrigo
  • Intertrigo Intertrigo describes the rash or inflammation that occurs where the body folds. Areas such as, under the arms, under the breast and other places are affected. Vitamin B6 deficiencies may lead to this condition.[naturalremedies.org]
  • If you eat three servings of mass-produced baked goods a day, you get enough vitamin B6 to prevent deficiency diseases, such as seborrhea (oily skin), intertrigo (rashes and ulcers in folds of skin), conjunctivitis (inflammation under the eye lids), chapped[healthifybody.com]
  • Eating just two to three servings of store-bought baked goods every day helps North Americans avoid the deficiency that can cause oily skin acne, seborrhea, dandruff, intertrigo (rashes in the folds of the skin), chapped lips, and conjunctivitis (itching[facingacne.com]
  • The classic clinical syndrome for B6 deficiency is a seborrheic dermatitis-like eruption, atrophic glossitis with ulceration, angular cheilitis, conjunctivitis, intertrigo, and neurologic symptoms of somnolence, confusion, and neuropathy (James et al.[newworldencyclopedia.org]
Irritability
  • Moderate and severe deficiency leads to the following symptoms: nervousness depression memory loss muscle weakness difficulty in concentration irritability Other serious complications of vitamin B6 lead to: occurrence of microcytic anaemia dermatitis[medasq.com]
  • Not having enough B6 can cause confusion, depression, irritability, and mouth/tongue sores. Low levels of vitamin B6 have been linked to chronic inflammation in the body. At home, check your mouth in a mirror.[sharecare.com]
  • .* This consisted of increased irritability, gastrointestinal distress, aggravated startle response, and convulsive seizures. The symptoms were shown to respond to pyridoxine therapy with both clinical and electroencephalographic improvement.[jamanetwork.com]
  • Are you challenged with irritability? Do you worry frequently? Are you feeling fatigued? If you answered yes to some or all of these questions, it is possible that you are experiencing a vitamin B6 deficiency .[brainmdhealth.com]
  • A lack of these vitamins can cause depression, irritability and trouble concentrating. Memory impairment may range from short-term memory loss and confusion to dementia.[livestrong.com]
Peripheral Neuropathy
  • We describe two patients who developed subacute axonal peripheral neuropathy under duodopa treatment.[ncbi.nlm.nih.gov]
  • When peripheral neuropathy is suspected in elderly patients on chronic peritoneal dialysis, vitamin B6 deficiency should be taken into consideration as the cause.[ncbi.nlm.nih.gov]
  • The telltale signal of a lack of vitamin B6, however, is often found in the peripheral neuropathy that it can cause, as well as anemia, seizures, and an effect similar to pellagra.[stop-being-tired.com]
  • neuropathy Cracked lips, sore mouth, inflamed tongue Depression and anxiety Carpal tunnel syndrome PMS and estrogen dominance Water retention; B6 acts as a natural diuretic and helps prevent water retention Insomnia Fatigue Weak neck flexors Morning[paulaowens.com]
  • Symptoms can include peripheral neuropathy, a pellagra-like syndrome, anemia, and seizures, which, particularly in infants, may not resolve when treated with anticonvulsants.[merckmanuals.com]
Paresthesia
  • In general, symptoms related to vitamin B6 deficiency are peripheral neuropathies, such as paresthesia, burning and painful dysesthesias, and thermal sensations. These symptoms were reported and assigned one of five grade scores.[ncbi.nlm.nih.gov]
  • Adverse Effects: Nausea, headache, paresthesia, somnolence and low serum folic acid concentrations have been reported. Sensory neuropathy can occur following long-term administration of large doses (2 g or more daily for 2 months or longer).[rxmed.com]
  • Symptoms such as numbness and paresthesias in the extremities, loss of position and vibratory sensation, difficulty walking, depression and irritability, diminished cognitive function (including memory impairment), and psychosis may be observed even in[journalofethics.ama-assn.org]
  • Vitamin B 5 pantothenic acid Deficiency can result in acne and paresthesia , although it is uncommon.[en.wikipedia.org]
Personality Change
  • Vitamin B - B2 and its deficiency leading Depression Although this vitamin itself has not generally associate with emotional states, researchers find that diets restricted only in riboflavin produce adverse personality changes, including aggressive personality[depression-guide.com]
Dysesthesia
  • In general, symptoms related to vitamin B6 deficiency are peripheral neuropathies, such as paresthesia, burning and painful dysesthesias, and thermal sensations. These symptoms were reported and assigned one of five grade scores.[ncbi.nlm.nih.gov]

Workup

Vitamin B6 deficiency should be a strong differential in any infant with seizures, patients with seizures unresolved by appropriate anticonvulsant therapy and in individuals with other B vitamin deficiencies.

Although there is no single accepted or standard diagnostic test for vitamin B6 deficiency, serum pyridoxal phosphate and urine/serum vitamin B6 assays provide an approximate measurement of vitamin B6 status.

Serum PLP level is the most reliable indicator of the body's vitamin B6 status. However, PLP levels should be measured with albumin levels to get correct values, as PLP levels depend on serum albumin levels [13]. Urine 4-pyridoxic acid also reflects the body's vitamin B6 status and can be used in the diagnosis of vitamin B6 deficiency. 4-pyridoxic acid is the main inactive metabolite of vitamin B6 and is excreted in the urine [14].

Nerve conduction tests and nerve biopsy (sural nerve) may be necessary to investigate neuronal function and pathologic changes. Nerve biopsy notably reveals axonal degeneration and demyelination of the nerves. EEG findings in infants with seizures induced by pyridoxine deficiency reveal high voltage, generalized and synchronous spikes of 1-4 Hz and sharp waves.

Hepatic Necrosis
  • Plasma levels of pyridoxal-5'-phosphate (PLP), the active coenzyme form of vitamin B6, were found to be significantly lower than normal in 22 out of 31 patients with decompensated cirrhosis or subacute hepatic necrosis.[ncbi.nlm.nih.gov]
  • Abstract Plasma levels of pyridoxal-5'-phosphate (PLP), the active coenzyme form of vitamin B6, were found to be significantly lower than normal in 22 out of 31 patients with decompensated cirrhosis or subacute hepatic necrosis.[gut.bmj.com]

Treatment

Treatment of vitamin B6 deficiency begins with identifying and correcting the underlying cause: pyridoxine should be co-administered with the inciting medications in patients receiving the latter, malabsorptive syndromes and chronic alcoholism should be well managed and dietary adjustments should be made.

Deficiencies due to high metabolic demand and inborn errors of metabolism of vitamin B6 require doses larger than the daily recommended ones. Treatment of the underlying diseases should be accompanied by concurrent pyridoxine therapy at a dose of 50-100mg PO daily. 30 - 50 mg pyridoxine should be prescribed for those receiving isoniazid.

Treatment should be administered with caution, however, because pyridoxine supplementation may cause toxic side effects including peripheral neuropathy. Toxicity is most common at high doses of the supplements. Lactating mothers and infants receiving pyridoxine supplements should particularly have their doses well monitored to prevent side effects.

Prognosis

Vitamin B6 deficiency responds well to treatment with little or no complications; however, the neonatal and infantile seizures may be unresponsive to anticonvulsant therapy.

Etiology

The causes of vitamin B6 deficiency can be categorized into 4 groups for descriptive purposes. These include inadequate dietary intake, conditions which interfere with the absorption of vitamin B6, diseases which cause increased loss of vitamin B6 and conditions or drugs which reduce the availability of the vitamin.

Dietary causes of vitamin B6 deficiency are rare because the vitamin is present in most foods, however, foods rich in vitamin B6 include fish, chicken, eggs, vegetables especially beans, fruits including avocados and oranges, and grains. Dietary deficiency of vitamin B6 may be more predominant in developing countries, where there are high incidence rates of chronic malnutrition. There's a daily recommended minimal requirement of vitamin B6 of 1.5 mg, although the US National research council recommends a minimal daily intake of 2.0 mg for adults and 0.3 mg for infants. Intake of processed foods, however, may cause vitamin B6 deficiency because food processing is associated with vitamin-depleting activities. For example, heat-treated foods contain an enzyme with anti-vitamin activity.

Malabsorption of vitamin B6 occurs in chronic alcoholism, protein-losing enteropathies, inflammatory bowel diseases, gastrointestinal surgeries and other malabsorption syndromes such as Celiac's disease [2] [3] [4].

The functions of vitamin B6 may be inhibited by medications which inhibit its actions. These drugs include isoniazid, cycloserine, hydralazine, corticosteroids, anticonvulsants and penicillamine. These drugs form complexes with the active form of vitamin B6 which impede its actions and also displace the active form of the vitamin from its binding site, rendering the vitamin functionally unavailable [5] [6] [7] [8]. Excessive loss of vitamin B6 is seen in individuals undergoing chronic dialysis and in liver diseases such as hepatitis, which increase the clearance rate of the vitamin [9]. Some medications also speed up the metabolism of vitamin B6.

Vitamin B6 deficiency can also be caused by conditions associated with a high metabolic rate such as pregnancy, lactation, and hyperthyroidism; however these causes are rare. Inborn errors of metabolism may also impede function and availability of the vitamin, causing symptoms due to pyridoxine deficiency.

Generally, it is rare to exhibit isolated vitamin B6 deficiency. B-vitamin deficiencies, especially caused by malabsorption, dietary insufficiency and increase loss all occur together.

Epidemiology

Pyridoxine deficiency can occur at any age without sexual predilection. However, the elderly are most at risk of developing the condition [10] [11]. This could be because of a higher daily requirement than can be met by one's diet, as the daily requirement of vitamin B6 increases with age. Seizures complicating pyridoxine deficiency are mostly seen in infants less than 3 months old, particularly neonates [8] [9].

Sex distribution
Age distribution

Pathophysiology

Pyridoxine, pyridoxal and pyridoxamine, which are forms of vitamin B6, are transported by facilitated diffusion into the hepatocytes after absorption. Pyridoxine and pyridoxamine are subsequently phosphorylated by pyridoxal kinase and converted to pyridoxal 5' phosphate (PLP) by a flavin-dependent enzyme.

PLP is an essential cofactor of a number of metabolic processes including decarboxylation, transamination, and pathways for lipid, amino acid, neurotransmitter, and carbohydrate synthesis. PLP is also an important coenzyme involved in amino acid metabolism, involving the production of tryptophan, methionine, and gamma aminobutyric acid (GABA). Therefore, a deficiency of vitamin B6 would cause symptoms related to the deficiency of these amino acids and to derangements in all metabolic pathways requiring pyridoxine.

Methionine deficiency results in the accumulation of S-adenosylmethionine, which inhibits myelin and sphingolipid synthesis. Tryptophan deficiency sequel to vitamin B6 deficiency may cause pellagra-like symptoms because of an impaired synthesis of niacin (tryptophan is an essential substrate for the production of niacin). With PLP being a cofactor for glutamic acid decarboxylase, its unavailability due to pyridoxine deficiency causes a reduced synthesis of GABA, eventually causing uninhibited neural firing, which is the basis of seizures in this condition [12].

Prevention

Vitamin B6 may be administered prophylactically to patients on medications which cause pyridoxine deficiency. Individuals who are on other medications which also interfere indirectly with pyridoxine-dependent processes should also receive pyridoxine; an example of this latter medication is estrogen, which interferes with tryptophan metabolism.

Daily doses of 10mg to 50 mg of pyridoxine are recommended for patients undergoing hemodialysis [15]. Patients on penicillamine should likewise receive 100mg PO of pyridoxine daily, and those on estrogen therapy should also ingest 20-25mg pyridoxine daily per os.

Generally, pyridoxine supplements should be administered in conditions which constitute risk factors for the development of pyridoxine deficiency.

Summary

Vitamin B6 is involved in a number of metabolic pathways including those for heme, nucleic acid, and neurotransmitter synthesis. Pathways for carbohydrate, lipid, and amino acid metabolism are also dependent on vitamin B6. Given the fact that it is an essential component for metabolic reactions, a deficiency of vitamin B6 also results in a lot of symptoms, cutting across various pathways and organ systems.

Vitamin B6 deficiency may result from poor dietary intake, poor absorption, functional unavailability or increased clearance of the vitamin. Conditions which are associated with a high metabolic rate also cause vitamin B6 deficiency. However, vitamin B6 deficiency usually occurs in combination with a deficiency of other B-vitamins.

Symptoms of vitamin B6 deficiency include neurological sequelae such as paresthesias (due to peripheral neuropathy), generalized convulsions, depression, irritability, glossitis and dermatitis [1].

Treatment involves the elimination of the underlying cause and administration of vitamin B supplements. Supplements are also co-administered with high-risk medications to prevent pyridoxine deficiency.

Patient Information

Vitamin B6 (pyridoxine) is a key factor involved in a number of processes in the body. It is required in order to process sugars, fats and amino acids in the body as well as for the proper function of the brain and nerve cells. It is also essential for the production of red blood cells which help carry oxygen in the blood.

Vitamin B6 deficiency often results from 4 groups of conditions including inadequate dietary intake of vitamin B rich foods, conditions which cause poor absorption of the vitamin in the gut, conditions which place a high demand on nutrients in the body, an example of which is breastfeeding and pregnancy, and conditions or drugs which increase the breakdown and excretion of the vitamin.

Dietary deficiency of vitamin B6 is quite rare because almost all foods contain Vitamin B6, and especially fruits, vegetables especially tomatoes and beans, and protein-rich foods such as fish and meat. There is a daily requirement of vitamin B6 of 1.5 mg every day, below which the body may show signs of deficiency, hence chronic malnutrition is a common cause of vitamin B6 deficiency.

Absorption of vitamin B6 can be tampered with by chronic alcohol consumption and diseases which destroy the gut's absorptive capacity. Examples of such diseases include inflammatory bowel diseases.

Medications which render vitamin B6 inactive in the body include steroids, anticonvulsants, isoniazid, a drug used for treating tuberculosis and hydralazine, an antihypertensive drug. These drugs affect the ability of the vitamin to function in the body.

Some genetic problems involving certain metabolic processes requiring pyridoxine may also cause abnormal functioning of vitamin B6. Usually, it is rare to have an isolated deficiency of vitamin B6. The other B-vitamins are usually also deficient at the same time, as some of the causes of vitamin B6 deficiency affect them as well.

The disease can occur at any age, however, the elderly are at a higher risk of developing vitamin B6 deficiency. It impairs a lot of processes in the body, particularly in the brain, causing convulsions, confusion, depression, irritability, pins and needles with numbness of the hands and feet. It can also cause anemia or shortage of red blood cells. The convulsions are most commonly seen in newborns and infants. Other prominent features are inflammation of the tongue (glossitis), which presents as soreness and redness of the tongue, and angular cheilitis which presents as cracks at the angles of the mouth.

Inflammation of the skin, called dermatitis, is another common feature of vitamin B6 deficiency, presenting as flaking and discoloration of the skin.

In the laboratory, although there is no standard test, there are some substances in the blood and urine which are products of vitamin B6 that can be measured to make a diagnosis of this condition. The nerves may also be analyzed by biopsy to evaluate specific changes which characterize this condition. Treatment involves eliminating or correcting the underlying cause and administering vitamin B6 supplements. The offending drug may not be changed, if there are no alternatives to it. In such cases, such individuals would also receive vitamin B supplements.

Patients receiving drugs that can cause vitamin B6 deficiency should also receive vitamin B6 supplements. Dietary adjustments should also be made to ensure they consume more foods rich in vitamin B6. Conditions or physiologic states which pose a risk of developing a deficiency of vitamin B6 should also be managed with vitamin B supplements to prevent the condition.

References

Article

  1. Ahmad I, Mirza T, Qadeer K, Nazim U, Vaid FH. Vitamin B6: deficiency diseases and methods of analysis. Pak J Pharm Sci. 2013 Sep;26(5):1057-69.
  2. Bowman BA, Russell RM.. Present Knowledge in Nutrition (9th Ed). Washington, DC: ILSI Press; 2006; 273
  3. Rall LC, Meydani SN. Vitamin B6 and immune competence. Nutr Rev. 1993 Aug;51(8):217-25.
  4. Massé PG, Boudreau J, Tranchant CC, Ouellette R, Ericson KL. Type 1 diabetes impairs vitamin B(6) metabolism at an early stage of women's adulthood. Appl Physiol Nutr Metab. 2012 Feb;37(1):167-75.
  5. Sauberlich H.. Vitamins - how much is for keeps? Nutr Today. 1987; 22:20-28
  6. Bhagavan HN.. Interraction between vitamin B6 and drugs. In Reynolds RD, Leklem JE, editors. . Vitamin B6: Its role in health and disease. New York: Liss. 1985: 401-415
  7. Heller CA, Friedman PA. Pyridoxine deficiency and peripheral neuropathy associated with long-term phenelzine therapy. Am J Med. 1983 Nov;75(5):887-8.
  8. Raskin NH, Fishman RA. Pyridoxine-deficiency neuropathy due to hydralazine. N Engl J Med. 1965 Nov 25;273(22):1182-5.
  9. Corken M, Porter J. Is vitamin B(6) deficiency an under-recognized risk in patients receiving haemodialysis? A systematic review: 2000-2010. Nephrology (Carlton). 2011 Sep;16(7):619-25.
  10. Kaczorowska M, Kmiec T, Jakobs C, et al. Pyridoxine-dependent seizures caused by alpha amino adipic semialdehyde dehydrogenase deficiency: the first Polish case with confirmed biochemical and molecular pathology. J Child Neurol. 2008 Oct 14.
  11. Striano P, Battaglia S, Giordano L, et al. Two novel ALDH7A1 (antiquitin) splicing mutations associated with pyridoxine-dependent seizures. Epilepsia. 2008 Aug 19.
  12. Kluger G, Blank R, Paul K, et al. Pyridoxine-dependent epilepsy: normal outcome in a patient with late diagnosis after prolonged status epilepticus causing cortical blindness. Neuropediatrics. 2008 Oct;39(5):276-9.
  13. Huang SC, Wei JC, Lin PT, Wu DJ, Huang YC. Plasma pyridoxal 5'-phosphate is not associated with inflammatory and immune responses after adjusting for serum albumin in patients with rheumatoid arthritis: a preliminary study. Ann Nutr Metab. 2012. 60(2):83-9.
  14. Baggot PJ, Eliseo AJ, DeNicola NG, Kalamarides JA, Shoemaker JD. Pyridoxine-related metabolite concentrations in normal and Down syndrome amniotic fluid. Fetal Diagn Ther. 2008. 23(4):254-7.
  15. Corken M, Porter J. Is vitamin B(6) deficiency an under-recognized risk in patients receiving haemodialysis? A systematic review: 2000-2010. Nephrology (Carlton). 2011 Sep;16(7):619-25.

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Last updated: 2018-06-22 01:35