Pyridoxine – Toxicity and Deficiency, and the balance between B6 and protein.

You could make an argument that the pyridoxine form of vitamin B6 is the only really dangerous vitamin supplement. Overdosing on anything else is unlikely if you stick to recommendations, but pyridoxine neuropathy is insidious and persistent and may happen at intakes as low as 200mg/day, and quite possibly lower (case history reporting neuropathy from 100mg/day taken for 10 years).

Axonal pathology is also a feature of the neuronopathies, toxic states in which the primary injuries are found in neuronal cell bodies. This is exemplified by pyridoxine neurotoxicity, where there is sublethal or lethal damage to larger cytons in the sensory ganglia, with failure of such neurons to maintain their axons.

In this brilliant study, the 5 volunteers were the study authors: a detectable neuropathy was induced by a 12mg/Kg/d dosage after 7 months.
However, other factors can increase sensitivity, especially protein deficiency.

Large doses of pyridoxine cause injury to the primary sensory neurons in trigeminal and dorsal root ganglia of animals and patients subjected to megavitamin therapy. The increased hazard to subjects with reduced renal excretory function has been explored previously. In the present work, the neurotoxicity of pyridoxine for rats was found to be increased by dietary protein deficiency. A mere 3 or 7 days of pretreatment with either of two protein-deficient diets were sufficient to accelerate and intensify the clinical neurological signs and histological lesions from pyridoxine injections. These results are caused, at least in part, by loss of body weight, decreased protein binding in serum and decreased consumption of water and decreased volume of urine, which reduce the urinary losses of the toxicant. The vitamers related to pyridoxine (pyridoxal, pyridoxamine) and the coenzyme (pyridoxal 5-phosphate) did not cause clinical signs or lesions similar to those produced by pyridoxine even when injected in maximum tolerated doses. Neither a protein-deficient diet nor bilateral nephrectomy changed the results with the vitamers.

Note that the vitamers (the animal forms of pyridoxine) and the co-enzyme P-5-P (PLP) were not toxic.

I strongly recommend using only vitamin supplements that contain P-5-P or one of the vitamers. A much lower dose can be effective if P-5-P replaces pyridoxine.

The relationship of B6 to protein is important because P-5-P is the coenzyme for most reactions involving amino acid metabolism or catabolism. To make niacin from tryptophan, nitric oxide from arginine, serotinon from tryptophan, cysteine from methionine via homocysteine, these and many more reactions of that type all require P-5-P. It is also required for glycogenolysis and phospholipid synthesis.

Meat, fatty fish, potatoes and bananas are all good B6 sources, but processed meat can be very low in B6 relative to how much protein it supplies. Low B6 status is one of the more common deficiencies detected when populations are studied. Could this be one of the reasons there is always an epidemiological difference between red meat and processed meat? Or could it just be that people who eat processed meats tend to have a greater appetite for, or tolerance of, processed rubbish in general?

The activation of pyridoxine to P-5-P requires riboflavin and magnesium, and deficiencies of these 2 nutrients, deficiencies which are in all conscience common enough (B2 is easily destroyed by UV light) could in theory also sensitize one to pyridoxine toxicity.

There are many features of amino acid metabolism in cirrhosis that suggest that activation of dietary pyridoxine to P-5-P by liver has become inadequate, and/or that the breakdown of P-5-P is excessive.
After administration of pyridoxine there was a significant increase in the plasma PLP level over a 2- to 12-hr period, after which the concentration returned gradually toward the initial value. The area under the concentration/time curve was from 2 to 8 times smaller (P less than 0.002) in the patients with liver disease. To assess possible mechanisms of this change, 5 mg of PLP were intravenously administered to the various patient groups and the pharmacokinetics of the disposition were assessed. The initial and steady state volumes of distribution of PLP were comparable in cirrhotics and controls (P greater than 0.05), but the clearance of plasma PLP in cirrhotics was much faster (63.0 +/- 7.4 versus 31.7 +/- 2.7 ml per min, P less than 0.004). Similar findings were obtained in the other liver disease subjects

There is an inverse association between dietary B6 and deep vein thrombosis.

Our study indicates that low vitamin B6 is associated with an increased risk of recurrent VTE. Until recently, the thrombotic risk associated with low vitamin status was entirely attributed to impaired homocysteine metabolism. But since doubts have been raised about the causal role of homocysteine in thrombotic disease,⁴ other functions of B vitamins need to be considered. Vitamin B6 is a co-enzyme in the metabolism of aminoacids, carbohydrates, neuro-transmitters and lipids,¹² and administration of vitamin B6 inhibits platelet function.¹³ Low vitamin B6 has also been related to elevated C-reactive protein levels and other markers of inflammation,¹⁴,¹⁵. In fact, patients with chronic inflammatory diseases, who are at heightened risk of VTE, exhibit low vitamin B6 levels.¹⁶

From personal experience, I can testify that years of overuse of pyridoxine, especially by someone who is not eating regularly, can result in long-lasting sensory problems even if the doses taken are those normally prescribed or recommended on line. This is not an exclusive problem of the supplement industry, as most of the pyridoxine I have used has been a prescription medication.

Pyridoxine neuropathy is likely to be missed in diagnosis and could even be misdiagnosed as early MS (the difference is that pyridoxine toxicity affects the body symmetrically, MS is asymmetrical). The visual disturbance is interesting and unusual; objects are doubled in the horizontal plane, like watching a 3d movie without the glasses. I still notice this slightly when I look at spires or poles in the middle distance, although the other symptoms have completely cleared, albeit very slowly. Ketogenic dieting was helpful. At one time I could barely read.

Pyridoxine has a fascinating effect on dream recall (very tempting for an opiate addict). Take enough of it, and the very dream changes; a dream that allows you completely perfect recall can be a very vivid but barren dream, with bare floors, little furniture, simple and repetitive architecture, and little in the way of characters or events. The orthomolecular theory is that inability to remember one’s dreams is indicative of pyridoxine deficiency. It is certainly corrected by B6.
Maybe, like DVT, it is caused by a diet too dependent on processed meat and refined carbohydrate.