Vitamin B6: pyridoxine hydrochloride vs. pyridoxal 5’-phosphate?

Ray - All I can say is Wow. I have gotten used to accepting there is “good” cholesterol (HDL) and “bad” cholesterol (LDL), but now trying to understand good B6 from bad B6 seems a bit unreasonably complicated for the average Joe trying to stay on top of their health labs. I’m in no position to question your doctor, but we should campaign for new names for the two B6’s to help distinguish them or for a major educational campaign from the FDA or NIH to help consumers. My B6 registered a little high when I was advised to add B supplements in 2016. Then a startled doctor said “Woah! Stop! Add B12 not B6!” They knew it was only high because I had it in the supplements I started taking, but we never discussed whether it was from hydrochloride or from phosphate. This Medical University just said whatever I’m adding, stop it. But that was 2016 - maybe they’ve learned more, or perhaps your doctor is more thoroughly reviewing your case. Either way, I think simplification is in order to help patients understand.

Hello again, Debbie. I'm guessing, as it's been since last night since I posed my question (pyridoxine vs. pyridoxal) and five hours since you posted the only response that the question of the possibility of two effectively distinct forms of B6 (as you summed up so perfectly: one "good" form and one "bad" form) is a question many people have not heard before. If that's true, it just deepens my perplexity. –Ray (@ray666)

Hi Ray, Did you see these? Not that I understand what they mean 🙃

--- What is the Difference Between Pyridoxal 5 Phosphate and Pyridoxine Hydrochloride: https://www.differencebetween.com/what-is-the-difference-between-pyridoxal-5-phosphate-and-pyridoxine-hydrochloride/
--- The vitamin B6 paradox: Supplementation with high concentrations of pyridoxine leads to decreased vitamin B6 function: https://pubmed.ncbi.nlm.nih.gov/28716455/

WOW! Thanks, John! Not that I'll do a better job of deciphering the medicalese.🙃 If nothing else, however, it'll keep me busy for the next few hours. Again, John, thank you so much for this! –Ray

Maybe also see:
https://www.consumerlab.com/answers/is-p-5-p-really-better-than-regular-vitamin-b6/pyridoxal-5-phosphate/

On the issue of B-6 - I did some research and found that a good number of the foods I eat on a consistent basis contain vitamin B-6. So, I thought why continue taking a B-6 supplement. About 3 weeks ago, with approval, I decided to stop taking B-6 supplements. I was on a low dosage. To my surprise, I feel that I have gained a little more feeling in both feet. I have sensory motor PN. Balance has not improved but it appears I can feel my feet a little better both sides and bottom. It took about 2 weeks before I felt a difference. Again, it is only a small improvement, perhaps about 5% to 10% but more important, the question is, will this slow down progression. Like most things, time will tell. Prior to going off B-6, I ran this past my nurse practitioner. Ed

Just to confirm there is a difference in (B6) toxic effects between Pyridoxal 5 Phosphate (P5P) and Pyridoxine Hydrochloride. I became concerned that my integrative health doctor prescribed a product "Prostate Flo",
that contained 10mg B6, even though he knew I have severe peripheral neuropathy. After further review, and reading some of the links provided in this venue, I found that the product contained pyridoxal 5' phosphate rather than the Pyridoxine form.
As stated in this article: https://pubmed.ncbi.nlm.nih.gov/36608063/
"PLP-based supplements are preferred over pyridoxine supplements because of minimal neurotoxicity observed in neuronal cell viability tests. Since B6 metabolites have a long half-life, weekly administration is preferred over daily use to prevent toxicity."

I hope this helps or at least provides clarity on B6 concerns.

Here's the answer...

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
Affiliations expand
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.

Welcome to Mayo Clinic Connect. Thank you for your comment.

Hi Ray,

You might have already found more info on that.
Just in case : The pyridoxine hydrochloride is the Synthetic Vitamin B6.Synthetic Vitamin B6 – Pyridoxine hydrochloride comes from petroleum ester, hydrochloric acid, and formaldehyde. It isn’t readily absorbed or converted and has been shown to actually inhibit the action of natural B6 in the body. It also has side effects not normally found with natural food sources of this vitamin. It has been found that long-term use of high doses of synthetic Vitamin B6 can cause neurological problems such as tingling and numbness in the hands and feet due to nerve damage caused by an accumulation of unmetabolized molecules from supplements.

Natural sources of vitamin B6 is Pyridoxal 5 phosphate, it's the active form of vitamin B6 refer primarily to food products derived from animal or plant sources which contain active concentrations of this micronutrient including poultry, beef liver, eggs, bananas, avocados and potatoes, red bell pepper (raw), pasilla peppers (dried - from Mexico), leafy greens like spinach and kale, dried shiitake mushrooms, chickpeas, sunflower seeds, pistachio nut.
Foods High In Vitamin B6

Natural forms of vitamin B6 are more likely to retain its bioactive components since they haven’t undergone any chemical processing prior to ingestion.

Dr. Janine talks about whole food vs synthetic vitamins looking specifically at Vitamin B6.

As a new member they didn't let me provide some links that I wanted to post. Might repost this in a few days or so.