Which Form of B6 Do You Need? A Simple At-Home Test
Hi all,
I want to start this article by immediately making it clear that not everyone requires supplemental B6. This is a very common mistake—and not an innocent one either.
Taking B6 when you don’t need it can lead to “toxicity” symptoms (for the record, I don’t agree with the mainstream understanding of B6 “toxicity” and absolutely believe it can be reversed much more quickly and effectively than by simply “waiting it out” and supporting hydration/vasodilation—the prevailing approach—but that’s another story).
Those “toxicity” symptoms generally begin as neuropathy, like the kind you get with diabetes: tingling in your toes and so on.
But some people absolutely do need B6 supplementation, whether due to genetic deficits (e.g. in ALPL, PDXK, PNPO, CBS, SLC19A1), chronic oxidative stress depleting PLP stores, impaired absorption from gut inflammation, or sustained functional demand from excessive neurotransmitter turnover, ammonia accumulation, or transsulfuration pathway activation.
Not getting enough B6 can lead to:
Relentless brain fog,
Crushing fatigue that sleep doesn’t fix,
Burning nerve pain or numbness in your hands and feet,
Insomnia despite exhaustion,
Mood swings that feel out of control,
Creeping anxiety,
Cracked lips,
Unexplained muscle twitches,
And even a sense that your body just isn’t recovering no matter what you do.
It’s a relatively simple fix if you know how to do it right—unfortunately, most doctors simply do not, at no fault of their own.
I recall a frustratingly painful moment during my medical training:
I was rotating in a headache clinic in South Florida, and a patient (let’s call her “Barbara”) came to us with years of near total inability to sleep.
If I recall correctly, Barbara was able to get no more than approximately 1–2 hours of sleep per night, despite doing everything that the doctors told her to do: sleep hygiene, melatonin, sedatives—none of it touched the deep, wired exhaustion she felt every night, as if her brain couldn’t change “modes” no matter how tired her body became.
Of course, that sleep issue was just a “side problem.”
Barbara’s real issue was the chronic, debilitating migraines she was getting over and over again, filling up her weeks and months—so many of her days gone to lying in bed, switching off the lights, and waiting for the pain to go.
The conventional doctors under which I was working put her on the standard migraine cocktail—triptans, beta blockers, and eventually some of the newer injectable CGRP inhibitors.
But this is yet another a prime example of how Modern Medicine (subconsciously) gets it wrong:
As I repeatedly say: Diseases are not “random” things that you just “get” without some actual systematic problems underlying those so-called diseases.
Barbara’s migraines and sleep issues were not some mystery issues totally detached from her biochemical and physiological makeup—thus requiring novel therapeutics and several-thousand-dollar CGRP inhibitors (I’ve been down that path with my own migraines).
I can say with full retrospective clarity: I just knew that there was something else underlying Barbara’s issue, and as I look back at it now, I highly suspect that issue was a matter of B6.
Why was there no consideration of the actual cause of her simultaneous migraines and sleep issues?
Why was there no concern for the reasons for her headaches and insomnia?
Rather than just pasting diagnostic “labels” upon our problems, we need to (1) figure out what’s causing our problems, then (2) treat the causes not the labels.
But am I saying that Barbara’s sleep issues and migraines have gone away with simple B6 supplementation?
Not necessarily.
Correcting B6 issues is surprisingly complex. For example, the dose required to alleviate B6-dependent issues is often the same dose that will cause B6-dependent toxicity.
In other words, B6 can be (and often is) simultaneous cure and toxin. (A full discussion of that is a topic for another day.)
Even further, there are different forms of B6, and choosing the right form is not as simple as some may make it seem.
Yes, P5P (pyridoxal-5-phosphate, also called PLP) is the biochemically “active” form…
But that doesn’t mean that P5P is the optimal form of vitamin B6 for everyone, contrary to what virtually all health gurus, doctors, and Reddit fiends online will tell you.
Why intestinal enzymes affect how you absorb B6 (specifically P5P)
The key player in this discussion is any enzyme (or group of enzymes) in your gut called IAP—intestinal alkaline phosphatases.
These enzymes are responsible for removing phosphates from some ingested vitamins, among other things.
P5P, the active form of B6, is called P5P because it has a phosphate group attached to it, which essentially makes it too big and charged to be absorbed across the digestive tract.
Instead, IAP has to remove that phosphate first, making vitamin B6 small enough to be absorbed across the digestive barrier effectively.
If for some reason your IAP is not functioning well (more common than you might expect—this can be caused by gut dysbiosis, gastric acid insufficiency, etc.) then you won’t be able to absorb P5P (again, active B6) because you can’t make it effectively “small” enough to get across the digestive barrier.
Of course, the ideal solution is to fix that aberrant IAP function and improve your intestinal absorption, but the problem is that sometimes a B6 deficiency itself may be contributing to the absorption issue.
In other words, your B6 deficiency itself may be limiting your ability to effectively absorb active B6!
In these cases, it becomes of high priority to optimize internal B6 concentrations prior to or simultaneous with correction of your absorption deficits.
In these cases, pyridoxine supplementation is of incredible value. It totally bypasses the absorption deficit and virtually ensures that you’re getting some B6 into your body (note: this is also a potential problem of pyridoxine, but that’s a deeper issue for another day. Ultimately: Test before supplementing at high doses).
But how do you know which form of B6 you’ll absorb most effectively—pyridoxine vs P5P?
Ultimately, such a decision is multifactorial, starting with actual plasma B6 testing +/- genetic testing of enzymatic B6-dependents +/- organic acid testing etc.
But I want to address the simple question here of easily determining whether you are effectively able to absorb P5P across the digestive barrier or require pyridoxine supplementation instead:
Because there’s no easy way to literally test your IAP function or “see” P5P crossing your digestive barrier, we’ll have to use a rough proxy:
Riboflavin-5-phosphate (R5P).
The fact is that riboflavin also comes in a more active form: the phosphate-bound form, just like B6.
But the difference is that you can actually tell—easily, and at home—whether riboflavin is getting into your bloodstream, unlike vitamin B6 (using a little test of my own invention).
Riboflavin has an intense yellow-green color that will visibly pigmen your urine when you supplement it. If R5P is being absorbed—indicating effective phosphate removal in the digestive tract and thus, by extension, the ability to do the same for P5P—then you’ll see a change in color in your urine, usually around 2-6 hours after ingestion of the capsule.
If you see no change in color of your urine, then you know that R5P was not able to get in your bloodstream, and thus you will likewise likely not absorb P5P effectively and may benefit from pyridoxine instead (if all other B6 activation factors are in place and you are determine to actually need B6).
So, in summary:
The protocol for determining which form of B6 you absorb better easily and at home:
Start with riboflavin-5'-phosphate (R5P): You can get THIS ONE, for example (no affiliation at all). This acts as a proxy for phosphorylated B-vitamins like P5P, since both require the same enzyme (intestinal alkaline phosphatase, IAP) for absorption.
On Day 1, take 25 mg of R5P on an empty stomach in the morning with a glass of water. Do not take any other B vitamins that day.
Monitor your urine color over the next 4–6 hours.
If your urine turns a bright yellow-green, that suggests your IAP is functioning well and you're likely absorbing phosphorylated forms like P5P efficiently.
If there is little or no color change, it may indicate poor IAP activity and reduced absorption of P5P and other phosphorylated B vitamins.
Take a rest day (no supplements) on Day 2.
On Day 3, repeat the test, this time using 25 mg of plain riboflavin (B2) instead of R5P. Again, monitor urine color for 4–6 hours.
Bright yellow urine here confirms that your kidneys are capable of excreting riboflavin, meaning any lack of color on Day 1 was likely due to poor R5P absorption, not poor excretion.
Optional Step for B6: If you're trying to determine which form of B6 you personally absorb best, you can repeat a similar test with:
P5P (25 mg) on Day 5, and
Pyridoxine HCl (10–25 mg) on Day 7
Track mood, energy, sleep quality for both, and any signs of nerve irritation or overstimulation.
Interpret the results:
If P5P improves symptoms and urine is bright after R5P, you likely absorb P5P well and can use it as your go-to form.
If P5P does little but pyridoxine works better, you may have low IAP but intact liver-based activation (PNPO function etc.).
If both forms cause symptoms or fail to help, consider testing serum PLP, OAT markers, or trialing pyridoxal (PL) directly.
Again, keep in mind that this test is not alone telling you whether you need to supplement with B6 of any form. But it is giving you a reasonably simple at-home way to determine whether you absorb the “bioactive” form of B6, P5P, which is pretty useful when you’re trying to address B6-dependent health issues that aren’t responsive to normal supplementation and coincide with gastrointestinal absorption problems.
As always, if you have any questions at all or want my help figuring out your so-called mystery medical problems, you have our email: admin@malekmd.com.
Thanks for reading.
Disclaimer: This article is for educational purposes only and does not constitute medical advice. It is not intended to diagnose, treat, cure, or prevent any disease. Always consult with a qualified healthcare provider before making decisions about supplements, treatments, or lifestyle changes, especially in the context of cancer or chronic illness.
