NeuroTalk Support Groups - View Single Post - Vitamin B6 Pyridoxine/P-5-P information:

mrsD · 10-29-2007, 08:15 AM

This thread will have information about this complex subject.

B6 is the most documented B vitamin in regards to toxicity. It is ironic that B6 deficiency causes a neuropathy. And that extreme excess of this vitamin also causes nerve damage.

I've gathered some links to illustrate both points.
I hope those interested here will read them carefully.

Here is a typical PubMed monograph about toxicity:

Quote:

Ned Tijdschr Geneeskd. 2005 Nov 12;149(46):2545-6.Links

Comment in:
Ned Tijdschr Geneeskd. 2005 Nov 12;149(46):2541-4.
Ned Tijdschr Geneeskd. 2006 Feb 4;150(5):277; author reply 277.
Ned Tijdschr Geneeskd. 2006 Feb 4;150(5):278; author reply 278.

[How much vitamin B6 is toxic?]
[Article in Dutch]

Katan MB.

Wageningen Centre for Food Sciences en Wageningen Universiteit, afd. Humane Voeding, Bomenweg 2, 6703 HD Wageningen. martijn.katan@wur.nl

Vitamin B6 (pyridoxine) causes neuropathy at intakes of 1000 mg per day or more, which is about 800 times the daily intake from foods. There have also been occasional reports of toxicity at intakes of 100-300 mg per day. The US authorities set the no-observed-adverse-effect-level at 200 mg per day and the safe upper limit at 100 mg per day. A report of neurotoxicity in 2 patients who had taken 24 mg and 40 mg of vitamin B6 per day respectively, may be coincidence rather than a true toxic effect of such relatively low doses. However, physicians need to remain alert to high intakes of vitamin B6 as a cause of unexplained neuropathy.

PMID: 16320662 [PubMed - indexed for MEDLINE]

Because some people cannot activate B6 because pyridoxal kinase is damaged or not working for some genetic reason, B6 doses in that very low range may be indicative of NO active pyridoxal reaching the tissues.

Here is a good link I found at a nutrition website:
http://drirene.healthandage.com/qa3/qa280132.htm

And this one explains P-5-P and states that P-5-P has yet to have reported toxicities:
http://www.encyclopedia.com/doc/1G1-71948217.html

There have been over the years posters here and at another similar site,
asking why their plasma values of B6 are elevated, even though they do not
take supplements. It appears to be a puzzle, and I have always answered that perhaps they are not converting to active pyridoxal normally, and hence the B6 is high in the serum. B6 is however excreted as a water soluble vitamin by the kidneys.
Then I found this paper, that illustrated autistic patients, have elevated B6 levels:

Quote:

J Altern Complement Med. 2006 Jan-Feb;12(1):59-63.Click here to read Links
Abnormally high plasma levels of vitamin B6 in children with autism not taking supplements compared to controls not taking supplements.
Adams JB, George F, Audhya T.

Arizona State University, Tempe, AZ 85287-6006, USA. jim.adams@asu.edu

BACKGROUND: There have been many studies of the effect of high-dose supplementation of vitamin B6 on children and adults with autism, with all but one reporting benefits. OBJECTIVE: The aim of this study was to investigate the biochemical basis for vitamin B6 therapy by measuring the level of total vitamin B6 in the plasma of unsupplemented children with autism spectrum disorder compared to unsupplemented control subjects. PARTICIPANTS: Children with autism spectrum disorders (n = 35, age 3-9 years) and unrelated typical children (n = 11, age 6-9 years), all from Arizona, were studied. (This includes the data from 24 children with autism from our previous study.) METHODOLOGY: A microbiologic assay was used to measure the level of total vitamin B6 (including phosphorylated and unphosphorylated forms), in a blinded fashion. RESULTS: Children with autism had a 75% higher level of total vitamin B6 than the controls (medians of 56 versus 32 ng/mL, respectively, p = 0.00002). Most of the autistic children (77%) had levels that were more than 2 standard deviations above the median value of the controls. The autistic girls (n = 5) also had elevated levels (mean of 54.6 ng/mL, median of 60 ng/mL). DISCUSSION: These results are consistent with previous studies that found that: (1) pyridoxal kinase had a very low activity in children with autism and (2) pyridoxal 5 phosphate (PLP) levels are unusually low in children with autism. Thus, it appears that the low conversion of pyridoxal and pyridoxine to PLP results in low levels of PLP, which is the active cofactor for 113 known enzymatic reactions, including the formation of many key neurotransmitters. CONCLUSIONS: Total vitamin B6 is abnormally high in autism, consistent with previous reports of an impaired pyridoxal kinase for the conversion of pyridoxine and pyridoxal to PLP. This may explain the many published studies of benefits of high-dose vitamin B6 supplementation in some children and adults with autism.

PMID: 16494569 [PubMed - indexed for MEDLINE]

Vitamin B6 is just very critical for our bodies to maintain health.
In the past there were experimental studies giving very high doses daily for PMS (500mg a day) and Carpal Tunnel Syndrome. The actual number of reported toxicities from these megadoses, was in the range of 15-20 patients, which is not really common. Given that people do not know their status of pyridoxal kinase, increasing doses past 100mg a day of regular pyridoxine, is not really going to increase one's response. So if you do not feel better, with B6 or if your homocysteine levels do not go down when you use it in conjunction with B12 and folic acid, then you need to consider taking the activated form called P-5-P. You may have to buy this online, but I have found it in stores, that carry, NOW brand aggressively. It is not as inexpensive as folic acid, but it is not really out of reach of most people, that is it is fair in price. A good quality P-5-P will be enteric coated to protect it from stomach acids.

There are a small number of people with a genetic disorder called pyridoxine dependency.
http://www.emedicine.com/ped/byname/...-syndromes.htm
This typically manifests in infancy as intractable seizures. And is reversed with very high doses of B6. This requires a doctor's supervision to find the dose of pyridoxine that works for each patient.

Also for pyroluria patients, B6 is critical. I suggest for these patients that P-5-P be used, since it is far more efficient biologically. 50mg/day is enough and any further increase in dose should be monitored by a doctor.

I had this link in my older B6 thread, and it is still active on the net:
http://www.nutrition4health.org/NOHAnews/NNSp99B6.html
and in this that link is this quote about P-5-P:

Quote:

I've heard criticisms that pyridoxal 5-phosphate is destroyed in the stomach or in the gut. These criticisms have come, without documentation,

Then next, the pyridoxine phosphate has to be oxidized by an oxidase enzyme that is assisted by vitamin B2, riboflavin, as flavin mononucleotide, "FMN." Here's one of the rubs in supplementing with pyridoxine. If vitamin B2 is low as FMN, then the rate of P 5-P production is typically decreased by 60%.

from pyridoxine fans. Actually, it's likely that some of the phosphate is knocked off. That's alkaline phosphatase's job--to rearrange the phosphate supply. But who cares? We've still got the pyridoxal--stomach won't make pyridoxine from pyridoxal. And once absorbed, the pyridoxal is more readily phosphorylated-according to the very authoritative enzymology reference cited earlier. And, the pyridoxal doesn't need FMN and another enzyme to reach the coenzyme form.

At the Klaire Laboratories International Symposium in Athens, Greece, in 1995, Dr. Emar Vogelaar reported on blood analyses of human subjects taking pyridoxal 5-phosphate. He found a better than 15% average increase in blood pyridoxal after two weeks of supplementation with 50 milligrams per day. So, there's no question about bioavailability-it gets in.

Finally, there's the problem of interfering vitamers in pyridoxine (substances that are similar to pyridoxine). At doses above 500 milligrams per day, peripheral or sensory neuropathy can occur in some individuals. This was widely reported over 10 years ago. Pyridoxine took the blame, but less publicized research later focussed the blame on vitamer impurities in the pyridoxine. Nothing is 100% pure, and pyridoxine is no exception: 4-deoxypyridoxine and methoxy-pyridoxine are known pyridoxine antagonists. However, when pyridoxine is carefully processed through several refinements to form pyridoxal 5-phosphate, the concentration of interfering vitamers drops substantially. Also, less P 5-P is needed than pyridoxine. No controlled studies have given exact comparisons, but I've found 50 milligrams per day of P 5-P to do the work of 200 to 500 milligrams of pyridoxine hydrochloride. Also, some case histories are worthwhile here. Several individuals presenting sensory neuropathy following high doses of pyridoxine had their conditions completely relieved by discontinuing the pyridoxine, taking no B6 in any form for 3 days, then taking 50 milligrams per day P 5-P for five days with no further symptoms.

To summarize, pyridoxal 5-phosphate has the advantages over pyrodoxine hydrochloride of:

* Being the actual coenzyme form,
* Avoiding the need of oxidation to pyridoxal, which requires FMN,___ which in turn has to be formed from vitamin B2 (riboflavin), which itself has to be phosphorylated-something that occurs in the intestinal mucosa and depends on proper mucosal function. And this phosphorylation of riboflavin is magnesium dependent.
* Pyridoxal phosphate may avoid phosphorylation, which may be zinc-dependent or magnesium-dependent in humans and could be a weak step if there is zinc or magnesium insufficiency.
* The P 5-P form is purer, and less is needed to achieve the same cofactor effects.
* To my knowledge no sensory neuropathy has ever been reported with use of P 5-P.

So, P 5-P has the edge over pyridoxine in magnesium deficiency, in zinc deficiency, in purity, and in potency.

Edit to add: Here is a paper from 1992...where 5 normal people were given massive doses of pyridoxine 1 to 3 grams/day (1000 to 3000mg)--all five reacted with nerve damage:

Quote:

Neurology. 1992 Jul;42(7):1367-70.Links
Dose response, coasting, and differential fiber vulnerability in human toxic neuropathy: a prospective study of pyridoxine neurotoxicity.
Berger AR, Schaumburg HH, Schroeder C, Apfel S, Reynolds R.

Department of Neurology, Albert Einstein College of Medicine, Bronx, NY.

We administered either 1 or 3 g/d of pyridoxine (vitamin B6) to five healthy volunteers and repeatedly followed serum pyridoxal phosphate levels, clinical symptoms and signs, quantitative sensory thresholds (QSTs), and sural nerve electrophysiology. Pyridoxine was discontinued at the first sign of either clinical or laboratory abnormality. In all subjects, sensory symptoms and QST abnormalities occurred concurrently. Subjects receiving higher doses became symptomatic earlier than low-dose subjects. Elevation of thermal QSTs preceded or exceeded that for vibration in the three low-dose subjects; vibration and thermal QST became abnormal simultaneously in the higher-dose subjects. A reduction in the amplitude of the sural sensory potential lagged behind QST changes in two of three subjects. Symptoms continued to progress ("coasting") for 2 to 3 weeks despite stopping pyridoxine administration and the return of serum pyridoxal phosphate levels to normal. This study suggests that (1) there is a clear dose-percent relationship for pyridoxine-induced neuropathy, (2) QST is a sensitive measurement for detecting early peripheral neuropathy; QST abnormalities may precede changes in nerve conduction studies, (3) coasting appears unrelated to persistently elevated blood levels of the toxin, and (4) a dose-dependent vulnerability may exist among nerve fibers of different caliber when exposed to an axonal toxin, such as pyridoxine.

PMID: 1620347 [PubMed - indexed for MEDLINE]