Pyridoxine deficiency and toxicity Domina Petric, MD

Pyridoxine deficiency November 20, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Pyridoxine deficiency Vitamin B6-deficient patients exhibit symptoms that can be quickly corrected by administration of the vitamin: weakness sleeplessness nervous disorders (peripheral neuropathies) cheilosis, glossitis, stomatitis impaired cell-mediated immunity November 20, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Pyridoxine deficiency signs Organ system/functions Signs Appetite Decreased Growth Dermatologic Acrodynia, cheilosis, stomatitis, glossitis Muscular Weakness Teeth Dental caries Vital organs Hepatic steatosis Vessels Arteriosclerosis Erythrocytes Anemia Reproductive Infertility, decreased fertility November 20, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Pyridoxine deficiency Because plasma concentrations of pyridoxal phosphate decrease with age, it is expected that elderly people may be at greater risk of vitamin B6 deficiency than younger people. November 20, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Pyridoxine deficiency Infants consuming less than 100 mg of vitamin B6 per day are at risk of developing seizures, which are thought to result from insufficient activities of the pyridoxal phosphate-dependent enzyme glutamate carboxylase required for the synthesis of GABA. November 20, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Homocysteinuria Hereditary deficiency of the cystathionine β-synthase occurs at a rate of 3/1,000,000. The resulting impairment in homocysteine catabolism is manifested as elevations in plasma levels of homocysteine, methionine and cysteine. Signs are dislocation of the optic lens, osteoporosis and abnormalities of long bone growth, mental retardation, thromboembolism. November 20, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Homocysteinuria The condition is treated with a low-methionine diet. Half of cases respond to high doses of pyridoxine: 250-500 mg/day November 20, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Ectopia lentis http://disorders.eyes.arizona.edu November 20, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Pyridoxine-responsive seizures This is a rare, autosomal recessive disorder involving impaired synthesis of the inhibitory neurotransmitter, γ-aminobutyric acid (GABA). Defect involves mutations in pyridoxine/pyridoxamine oxidase. The disorder is manifested as intractable seizures appearing within hours after birth. November 20, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Pyridoxine-responsive seizures Patients show normal circulating levels of pyridoxal phosphate, but their seizures stop immediately upon administration of high levels (100-500 mg) of pyridoxine intravenously and are controlled using daily oral doses of pyridoxine (0.2-3 mg/kg body weight). If untreated, progressive cerebral atrophy ensues. November 20, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Hyperoxaluria Type 1 primary hyperoxaluria has been found to be due to a mutant hepatic alanine glyoxylate transferase with abnormally low pyridoxal phosphate-binding capacity. In such cases high doses of vitamin B6 (400 mg/day) reduce hyperoxaluria and thus the risk of formation of oxalate stones and renal injury. November 20, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Pharmacologic uses of pyridoxine II. November 20, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Sideroblastic anemia Dosages as great as 200 mg/day (usually as pyridoxine HCl) have been found effective in stimulating hematopoesis (δ-aminolevulinic acid synthase) in sideroblastic anemia patients. November 20, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Sickle cell anemia A small study found patients to have lower plasma pyridoxal phosphate levels than controls, which responded to oral supplementation (100 mg/day) of pyridoxine within two months. Both pyridoxine and pyridoxal phosphate have been found to protect sickle cells in vitro. November 20, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Iron storage disease Complexes of pyridoxal, which chelate iron (the isonicotinyl and benzoyl hydrazones), are effective in stimulating the excretion of that mineral in patients with iron storage disease. November 20, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Suppression of lactation A few studies have reported vitamin B6 as effective in suppressing lactation, probably through the stimulation of dopaminergic activity in the hypothalamus and thus the suppression of prolactin. November 20, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Adverse drug effects The vitamin is used (3-5 mg/kg body weight) to counteract adverse effects of several types of drugs. November 20, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Hydrazines The antituberculin drug isonicotinic acid hydrazide (isoniazid) produces a peripheral neuropathy similar to that of vitamin B6 deficiency. It inhibits pyridoxal phosphate-dependent glutamate-decarboxylase and γ-aminobutyrate aminotransferase which produce and degrade GABA in the nerve tissue. November 20, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Antibiotics Cycloserine reacts with the coenzyme to produce an oxime. Two antibiotics have been found to antagonize vitamin B6 by reacting with pyridoxal phosphate to form inactive products. Cycloserine reacts with the coenzyme to produce an oxime. Penicillamine produces thiazolidine. November 20, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

L-DOPA L-3,4-dihydroxyphenylalanine antagonizes vitamin B6 by reacting with pyridoxal phosphate to form tetrahydroquinolines. November 20, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Ethanol increases the catabolism of pyridoxal phosphate. November 20, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Oral contraceptives Synthetic estrogens can alter tryptophan-niacin conversion by increasing the synthesis of pyridoxal phosphate dependent enzymes in that pathway and increase the need for vitamin B6 in some subjects. November 20, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Other pharmacologic uses November 20, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Vitamin B6 may be useful for the reduction of seizures in alcoholics. Schizophrenia Vitamin B6 is recommended (0.1-1 g/day alone or in combination with tryptophan or magnesium) for the treatment of schizophrenia. Vitamin B6 may be useful for the reduction of seizures in alcoholics. November 20, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Asthma Low circulating pyridoxal phosphate levels have been reported in patients with asthma. One small study found vitamin B6 treatment (100 mg/day) to reduce the severity and frequency of attacks. These effects may be secondary to those of theophylline, which inhibits pyridoxal kinase. November 20, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Herpes Pyridoxine has been used to treat herpes gestationis at doses of 400-4000 mg/day. November 20, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Carpal tunnel syndrome The syndrome, involving pain and paresthesia of the hand, is caused by irritation and compression of the medial nerve by the transverse ligaments of the wrist in ways that are exacerbated by redundant motions. The condition has been associated with low circulating levels of pyridoxal phosphate and low erythrocyte glutamic-oxaloacetic transaminase activities. November 20, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Carpal tunnel syndrome High doses of pyridoxine might be effective as treatment: 50-300 mg/day for 12 weeks. November 20, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Chinese restaurant syndrome The syndrome, which involves headache, sensation of heat, altered heart beat, nausea, and tightness of the neck induced by oral intake of monosodium glutamate, has been reported to respond to vitamin B6 (50 mg/day). November 20, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Premenstrual syndrome Occurs in an estimated 40% of women 2-3 days before their menstrual flow. It involves tension of the breasts, pain in the lumbar region, thirst, headache, nervous irritability, pelvic congestion, peripheral edema, and, usually, nausea and vomiting. November 20, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Premenstrual syndrome Premenstrual syndrome has been reported to respond to vitamin B6, presumably by affecting levels of the neurotransmitters, serotonin and γ-aminobutyric acid, which control depression, pain perception and anxiety. November 20, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Morning sickness A randomized clinical trial showed that the use of pyridoxine (25 mg every eight hours for three days) significantly reduced vomiting and nausea in pregnant women. November 20, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Pyridoxine toxicity III. November 20, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Pyridoxine toxicity The toxicity of vitamin B6 appears to be relatively low. High doses of the vitamin (several grams per day) have been shown to induce sensory neuropathy marked by changes in gait and peripheral sensation. November 20, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Pyridoxine toxicity In doses of 10-25 mg, vitamin B6 increases the conversion of L-dopa to dopamine, which is unable to cross the blood-brain barrier. The vitamin can therefore interfere with L-dopa in the management of Parkinson’s disease. It should not be administered to individuals taking L-dopa without the concomitant administration of a decarboxylase inhibitor. November 20, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Literature Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008. November 20, 2018