There was a relation between polyneuropathy and diabetes, hyperglycaemia and body height. No relation to homocysteine level was found. Vitamin B12, folat or B6 were not measured. However, they estimated vitamin B6 intake based on a dietary history model. Surprisingly, the intake of B6 was higher in individuals with polyneuropathy. A history of taking B6 supplements was also more common.

This is the first time this interaction has been found in a study of this kind. It has been reported earlier that prolonged intake of B6 in high doses (>500 mg/day) might result in sensory nerve damage (3). In some cases 200 mg/day are reported having harmed sensory nerve function (4). In this study (2), intake of B6 was not of this magnitude.

As an explanation to the findings, neurotoxicity was considered but the intake of B6 was considered safe. Another reason could be increased intake of vitamins, e.g. B6, among individuals with symptoms of polyneuropathy.

Contemplating this information (2-4), some help might be found studying the metabolism of methionine and homocysteine that is intimately related to B12, folate and B6, see figure on top.

S-Adenocylmethionine (SAM) is a key substance for nerve function in the central and peripheral nerve system. SAM is the most important methyl donor in the body and is needed for e.g. myelination of nerve sheaths and for the production of a number of neurotransmittors. SAM regulates remethylation of homocysteine to methionine by feedback mechanisms. When SAM is abundant remethylation is down-regulated and the B6-dependent transsulfuration pathway is stimulated to degrade homocysteine. When there is a deficiency of SAM, remethylation is up-regulated and transsulfuration is slowed down. When there is a deficiency of B12 and/or folate, there is a deficiency of SAM, which is thought to contribute to neurological damage.

It is a well-known fact that a deficiency of B12 and/or folate should not be treated with folic acid as a single drug. This might result in progress of neurological symptoms, as the defect in remethylation is not put back into working order. Less known is the fact that B12 as a single drug does not cure a deficiency of folate and/or B12. In some cases treatment with B12 only might result in neurological damage, as the remethylation is still not functioning properly. An increased B6-mediated degradation of homocysteine might theoretically impair remethylation, resulting in decreased SAM levels. The efficiency or inefficiency of SAM to regulate the metabolism if there is a subclinical deficiency of folate and/or B12 is not clear. The liver and kidneys might have a role in this process, as it is these organs that mainly degrade homocysteine by the B6-dependent transsulfuration pathway. Transsulfuration is considered not to occur in the nerve system.

There is no perfect solution to the problem of B6 and polyneuropathy at this time. At least three B-vitamins are needed for a normal nerve function. A balanced intake of these three vitamins is crucial. Toxic effects, not related to this metabolism, might be seen after un-physiological mega doses of vitamin B6.

(1) Ekstedt J. Polyneuropathia in primary health care. The Rondel, vol 3, March-June 2000. (www.rondellen.net).

(2) Hoogeveen E.K. Kostense P.J., Valk G.D., Bertelsmann F.W. Jacobs C., Dekker J.M., Nijpels G., Heine R.J., Bouter L.M., & Stehouver C.D.A. Hyperhomocysteinemia is not related to risk of distal somatic polyneuropathy: The Hoorn Study. Journal of Internal Medicine, 1999; 561-566.

(3) Cohen M. and Bendich A. Safety of pyridoxine – a review of human and animal studies. Toxicol Lett, 1986, 34; 129-39.