Vitamin B6 Toxicity

What Is Vitamin B6?

Vitamin B6 is an essential micronutrient that is needed by the body. It is a water-soluble vitamin that is present in food as well as dietary supplements. It is a generic name that denotes various chemically similar compounds, of which pyridoxine is the most common one, and pyridoxine is the one that is present in dietary supplements.

Vitamin B6, in its coenzyme form, is involved in more than a hundred enzymatic reactions, mostly linked to protein metabolism. Vitamin B6 is involved in the biosynthesis of neurotransmitters and hence plays a role in cognitive development. It is also involved in hemoglobin formation, glycogenolysis (a metabolic pathway in which glycogen is broken down to glucose), gluconeogenesis (glucose generation from non-carbohydrate precursors), and immune function.

Absorption of Vitamin B6 takes place through passive diffusion in the jejunum. The main food sources of the vitamin are potatoes, non-citrus fruits, fortified cereals, salmon, banana, beef liver, poultry, starchy vegetables, etc.

What Are the Causes of Vitamin B6 Toxicity?

The most common cause of Vitamin B6toxicityis supratherapeutic dosing. The supratherapeutic dosing can either be iatrogenic (physician-induced) or due to self-treating by laypersons with over-the-counter supplements. Taking pyridoxine through food sources is not known to cause any toxicity. The daily dietary Vitamin B6 intake in the United States is around 1.9 mg/day.

On the other hand, the average pyridoxine dose used for co-treatment with isoniazid medication is 10 to 25 milligrams per day. Pyridoxine is used as an antidote in supratherapeutic doses for treating seizures due to isoniazid toxicity. It is used Within the therapeutic range for treating hyperemesis gravidarum (an extreme case of morning sickness leading to weight loss and volume depletion) as a dietary supplement.

Laypersons use pyridoxine for conditions like depression, morning sickness, premenstrual syndrome, etc. Intake of over-the-counter supplements by laypersons is the main culprit for intake of pyridoxine above the safe recommended level.

What Are the Clinical Features of Vitamin B6 Toxicity?

The symptoms associated with Vitamin B6 toxicity mimic those associated with Vitamin B6 deficiency.

The symptoms experienced are:

• Numbness over the extremities.

• Heartburn.

• Nausea.

• Dermatological lesions.

• Sensitivity to light.

• Ataxia (a condition in which one loses control over bodily movements).

• Bone pain.

• Muscle weakness.

• Fasciculation or involuntary muscle movement.

• Hyperesthesia (increased sensitivity to sensations like touch, sound, light, or smell).

Vitamin B6 toxicity results in peripheral sensory neuropathy, a condition in which nerves in the extremities get damaged. The symptom severity is dose-dependent.

What Is Toxicokinetics?

After taking pyridoxine orally, the peak plasma level is reached in an hour. Within the liver, the absorbed form of B6 is converted into PLP (pyridoxal 5- phosphate). It binds to albumin and is transported in the serum. The oral doses of 100 milligrams of pyridoxamine, pyridoxine, and pyridoxal are excreted unchanged in the urine.

Vitamin B6 is known to have several drug interactions. These drugs usually lower pyridoxine levels, leading to vitamin B6 deficiency rather than toxicity. Cyclosporine, isoniazid, L-dopa, penicillin, etc., form complexes with Vitamin B6 and reduce the bioavailability of the vitamin. High doses of pyridoxine lower the blood level of phenobarbital and phenytoin.

What Is the Maximum Limit?

The Food and Nutrition Board (FNB) has set upper limits for both food and dietary intake of Vitamin B6. UL is the “tolerable upper intake level,” the maximum daily intake that can be taken without causing adverse health effects. Due to data limitations on the potential harm of vitamin B6 in long-term use, the FNB set the UL by halving the dose in studies. For adults, UL is 100 milligrams per day.

However, the UL values do not apply to individuals under medical therapy. In such cases, a dose the physician recommends should be taken.

For children from 1 to 3 years, UL is 30 milligrams. For children of age 4 to 8 years, UL is 40 milligrams. For children 9 to 13 years, UL is 60 milligrams, and for those between 14 to 18 years, UL is 80 milligrams. For those above 18 years, UL is 100 milligrams.

How Is the Toxicity Evaluated?

On physical examination and history taking, the patient presents with neurological symptoms due to sensory neuropathy associated with the toxicity. The patient should be asked whether they have taken over-the-counter supplements; if yes, they should be asked to bring the medication. This is because different supplements have different doses of pyridoxine, and the exact amount taken can be evaluated.

A thorough neurological examination that includes reflexes, gait, muscle strength, motor, sensory, and cranial nerve testing should be done. Mainly, the patient presents with motor or sensory changes on both sides. Unilateral presentation is seen in cases of past neurological injury.

How Is the Toxicity Managed?

There is no antidote or specific treatment for vitamin B6 toxicity. Cessation of the supplementation, supportive care, and symptomatic management are the options.

What Is the Differential Diagnosis?

Differential diagnoses include deficiencies and toxicities of other vitamins, including deficiency of vitamin B12. Other conditions causing peripheral neuropathy also come under differential diagnosis. Nerve conduction velocity tests, exposure history, and additional lab tests may be required to rule out other etiologies.

The differential diagnosis includes:

• Diabetes mellitus.

• HIV (human immunodeficiency virus).

• Hypothyroidism.

• Chronic liver disease.

• Drugs.

• Autoimmune disorders.

• Lymphoma.

• Lyme disease.

What Is the Prognosis?

Vitamin B6 toxicity mostly has a favorable prognosis. The symptoms decrease or resolve once the symptoms are identified and cessation of supratherapeutic pyridoxine is carried out. However, neuropathy due to massive exposure may lead to disability. The neurological symptoms resolve with cessation of supplementation, and the dysfunction resolves in about six months. However, some patients may not recover.

Conclusion

Vitamin B6 toxicity occurs due to supratherapeutic dosage, mainly due to overconsumption of supplements. The symptoms mimic that of vitamin B6 deficiency and are mostly due to peripheral neuropathy that occurs due to the toxicity. There is no antidote for the toxicity; only symptomatic management and supplement cessation are the management measures.