Megavitamin-B₆ syndrome

Megavitamin-B₆ syndrome, also known as hypervitaminosis B₆, vitamin B₆ toxicity, and vitamin B₆ excess,

The syndrome is notable not only for its impact on peripheral nerve function but also because of its generally, but not always, reversible nature upon cessation of vitamin B₆ intake. Usually, but not always, cases resolve within six months after stopping the vitamin B₆ supplementation, although some symptoms can intensify briefly after cessation—a phenomenon known as "coasting." Diagnosis typically involves serum tests to measure elevated levels of vitamin B₆, along with nerve conduction studies and other neurodiagnostic evaluations.[4]^[14][15][16]

This condition underscores the importance of moderation in the use of dietary supplements, highlighting that even substances generally safe at recommended dosages can lead to serious health issues if taken excessively.^[23]

Signs and symptoms

The predominant symptom is

Symptom severity appears to be dose-dependent (higher doses cause more severe symptoms)^[26] and the duration of supplementation with vitamin B₆ before the onset of systems appears to be inversely proportional to the amount taken daily (the smaller the daily dosage, the longer it will take for symptoms to develop).^{[15][4][10][12][7]} It is also possible that some individuals are more susceptible to the toxic effects of vitamin B₆ than others.^[4] Megavitamin-B₆ syndrome has been reported in doses as low as 24 mg/day.^[33]

Symptoms may also be dependent on the

Early diagnosis and cessation of vitamin B₆ supplementation can reduce the morbidity of the syndrome.^[26][12]

Cause

While vitamin B₆ is water-soluble, it accumulates in the body. The half-life vitamin B₆ is measured at around two to four weeks,^[39][40] it is stored in muscle, plasma, the liver, red blood cells and bound to proteins in tissues.^[39][41][42]

Potential mechanisms

The common supplemental form of vitamin B₆, pyridoxine, is similar to

Several government agencies have reviewed the data on vitamin B₆ supplementation and produced consumption upper limits with the desired goal of preventing sensory neuropathy from excessive amounts. Each agency developed its own criteria for usable studies concerning tolerable upper limits, and as such, the recommendations vary by agency. Between agencies, current tolerable upper limit guidelines vary from 10 mg per day to 100 mg per day.[39]

Reviews of vitamin B₆ related neuropathy cautioned that supplementation at doses greater than 50 mg per day for extended periods may be harmful and should be discouraged.^[48][49] In 2008, the Australian Complementary Medicines Evaluation Committee recommended warning statements appear on products containing daily doses of 50 mg or more vitamin B₆ to avoid toxicity.^[50]

The relationship between the amount of vitamin B₆ consumed and the serum levels of those who consume it varies between individuals.^[51] Some people may have high serum concentrations without neuropathy symptoms.^[13][52][53] It is not known if inhalation of vitamin B₆ while, for example, working with animal feed containing vitamin B₆ is safe.^[54]

Exceptions

High parenteral doses of vitamin B₆ are used to treat isoniazid overdose with no adverse effects found,^[4] although a preservative in parenteral vitamin B₆ may cause transient worsening of metabolic acidosis.^[4] High doses of vitamin B₆ are used to treat gyromitra mushroom (false morel) poisoning, hydrazine exposure and homocystinuria^[8][55] Doses of 50 mg to 100 mg per day may also be used to treat pyridoxine deficient seizures and when patients are taking other medications that reduce vitamin B₆.^[14] Daily doses of 10 mg to 50 mg are recommended for patients undergoing hemodialysis.^[14]

Outside of rare medical conditions, placebo-controlled studies have generally failed to show benefits of high doses of vitamin B₆.^[28] Reviews of supplementing with vitamin B₆ have not found it to be effective at reducing swelling, reducing stress, producing energy, preventing neurotoxicity, or treating asthma.^[23]

Diagnosis

The clinical hallmark of megavitamin-B₆ syndrome is ataxia due to sensory polyneuropathy. Blood tests are performed to rule out other causes and to confirm an elevated level of vitamin B₆ with an absence of hypophosphatasia.^{[14][11][12][56][57]} Examination does not typically show signs of a motor deficit, dysfunction of the autonomic nervous system or impairment of the central nervous system,^[4][3] although in severe cases motor and autonomic imparement can occur.^[14][12][58] When examined, patients typically have diminished reflexes (hyporeflexia), such as a diminished response when performing an ankle jerk reflex test.^[14][24][3] Nerve conduction studies typically show normal motor conduction but a decrease in large sensory wave amplitude in the arms and legs.^{[24][10][14][13][3]} Needle electromyography studies generally reveal no signs of denervation.^[15]

Classification

Megavitamin-B₆ syndrome is characterized mainly by degeneration of

The primary treatment for megavitamin-B₆ syndrome is to stop taking supplemental vitamin B₆.[14] Physical therapy, including vestibular rehabilitation, has been used in attempts to improve recovery following cessation of vitamin B₆ supplementation.^[50][11] Medications such as amitriptyline have been used to help with neuropathic pain.^[19]

In experimental tests using animal subjects,

Other than with extremely high doses of vitamin B₆, neurologic dysfunction improves following cessation of vitamin B₆ supplementation and usually, but not always, resolves within six months.[3]^[4] In cases of acute high doses, for example in people receiving daily doses of 2 grams of vitamin B₆ per kilogram of body weight, symptoms may be irreversible and may additionally cause pseudoathetosis.^{[3][15][19][16][6][8]}

In the immediate 2–6 weeks following discontinuation of vitamin B₆, patients may experience a symptom progression before gradual improvement begins. This is known as coasting and is encountered in other toxic neuropathies.^{[14][4][15][16]} A vitamin B₆ substance dependency may exist in daily dosages of 200 mg or more, making a drug withdrawal effect possible when discontinued.^[23]

See also

Notes

References