helvella - Vitamers of Vitamin B6

Some time ago, I mentioned that the form in which we take vitamin B6 is important. I think I linked to this paper:
 

Toxicol In Vitro . 2017 Oct;44:206-212.
doi: 10.1016/j.tiv.2017.07.009. Epub 2017 Jul 14. 

The vitamin B6 paradox: Supplementation with high concentrations of pyridoxine leads to decreased vitamin B6 function
Misha F Vrolijk  1 , Antoon Opperhuizen  2 , Eugène H J M Jansen  3 , Geja J Hageman  4 , Aalt Bast  4 , Guido R M M Haenen  4

    • PMID: 28716455
    • DOI: 10.1016/j.tiv.2017.07.009
Abstract
Vitamin B6 is a water-soluble vitamin that functions as a coenzyme in many reactions involved in amino acid, carbohydrates and lipid metabolism. Since 2014, >50 cases of sensory neuronal pain due to vitamin B6 supplementation were reported. Up to now, the mechanism of this toxicity is enigmatic and the contribution of the various B6 vitamers to this toxicity is largely unknown. In the present study, the neurotoxicity of the different forms of vitamin B6 is tested on SHSY5Y and CaCo-2 cells. Cells were exposed to pyridoxine, pyridoxamine, pyridoxal, pyridoxal-5-phosphate or pyridoxamine-5-phosphate for 24h, after which cell viability was measured using the MTT assay. The expression of Bax and caspase-8 was tested after the 24h exposure. The effect of the vitamers on two pyridoxal-5-phosphate dependent enzymes was also tested. Pyridoxine induced cell death in a concentration-dependent way in SHSY5Y cells. The other vitamers did not affect cell viability. Pyridoxine significantly increased the expression of Bax and caspase-8. Moreover, both pyridoxal-5-phosphate dependent enzymes were inhibited by pyridoxine. In conclusion, the present study indicates that the neuropathy observed after taking a relatively high dose of vitamin B6 supplements is due to pyridoxine. The inactive form pyridoxine competitively inhibits the active pyridoxal-5'-phosphate. Consequently, symptoms of vitamin B6 supplementation are similar to those of vitamin B6 deficiency.
Keywords: Neuropathy; Neurotoxic; Pyridoxine; Supplements; Vitamin B6.

Full paper is, unfortunately, behind a paywall:

https://pubmed.ncbi.nlm.nih.gov/28716455/


In the paper, they define mega doses as > 50. And the low doses at which negative effects have been noticed being as little as 2. The conclusion of the paper says:

In conclusion, the present study strongly indicates that the neuropathy observed after taking a relatively high dose of vitamin B6 supplements is due to the vitamer that is used in the supplements, namely pyridoxine. The inactive form pyridoxine competitively inhibits the active pyridoxal-phosphate. As a consequence, the paradox arises that the symptoms of vitamin B6 supplementation are similar to those of vitamin B6 deficiency. Vitamin B6 supplements are used by a large number of people. The safety of vitamin B6 is debated and recently EFSA has lowered the upper limit for vitamin B6. The question is whether lowering the safe dose for vitamin B6 is the solution. Remarkably, even at relatively low dose, vitamin B6 supplementation has given rise to complaints. Our study indicates that the toxicity of vitamin B6 is not only determined by the dose, but by the vitamer in which it is taken. Perhaps it might be better to replace pyridoxine by pyridoxal or pyridoxal-phosphate as vitamin B6 supplements, which are much less toxic. In this way, the vitamin B6 paradox may potentially be prevented.

I'd rather play safe and avoid any pyridoxine in supplements.

Scientific opinion on the tolerable upper intake level for vitamin B6 

Abstract

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver a scientific opinion on the tolerable upper intake level (UL) for vitamin B6. Systematic reviews of the literature were conducted by a contractor. The relationship between excess vitamin B6 intakes and the development of peripheral neuropathy is well established and is the critical effect on which the UL is based. A lowest‐observed‐effect‐level (LOAEL) could not be established based on human data. A reference point (RP) of 50 mg/day is identified by the Panel from a case–control study, supported by data from case reports and vigilance data. An uncertainty factor (UF) of 4 is applied to the RP to account for the inverse relationship between dose and time to onset of symptoms and the limited data available. The latter covers uncertainties as to the level of intake that would represent a LOAEL. This leads to a UL of 12.5 mg/day. From a subchronic study in Beagle dogs, a LOAEL of 50 mg/kg body weight (bw) per day can be identified. Using an UF of 300, and a default bw of 70 kg, a UL of 11.7 mg/day can be calculated. From the midpoint of the range of these two ULs and rounding down, a UL of 12 mg/day is established by the Panel for vitamin B6 for adults (including pregnant and lactating women). ULs for infants and children are derived from the UL for adults using allometric scaling: 2.2–2.5 mg/day (4–11 months), 3.2–4.5 mg/day (1–6 years), 6.1–10.7 mg/day (7–17 years). Based on available intake data, EU populations are unlikely to exceed ULs, except for regular users of food supplements containing high doses of vitamin B6.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10189633/

For a general background to vitamin B6, the Office of Dietary Supplements produces sheets on B6 as well as many other common supplements.

Home > Health Information > Dietary Supplement Fact Sheets > Vitamin B6 > Vitamin B6 - Health Professional

Vitamin B6

Fact Sheet for Health Professionals 

https://ods.od.nih.gov/factsheets/VitaminB6-HealthProfessional/

 

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[i][b]helvella - Vitamers of Vitamin B6 [/b]

Some time ago, I mentioned that the form in which we take vitamin B6 is important. I think I linked to this paper:[/i]

https://helvella.blogspot.com/p/helvella-vitamers-of-vitamin-b6.html

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