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

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Vitamin B6 Pyridoxine/P-5-P information:

I've been meaning to start an informational thread here for Vitamin B6 Pyridoxine. So here it is.

Please feel free to post here anything you feel is helpful to the subject, or ask questions. I will be adding to this thread frequently as I consolidate data that I find.

Many years ago, over 10 actually, I started posting about P-5-P on various health boards. This is an activated form of pyridoxine which is the form the body actually uses. Pyridoxine in most vitamins has to be converted to this form. That process may be inhibited by liver damage, or use of certain drugs (theophylline). Those interested in chemistry can view Pyridoxine here:
http://web.indstate.edu/thcme/mwking/vitamins.html

Today we have a new RX vitamin that contain P-5-P. It is called Metanx (promoted for neuropathies and homocysteine defense).
When looking at labels, look for the words coenzymated B6 as an ingredient.
The best manufacturers enteric coat their P-5-P like NOW brand does.

For now I'd like to give some links to B6 information.
This one is very good, and run by NIH
http://ods.od.nih.gov/factsheets/vitaminb6.asp

Another great source is The Linus Pauling Institute:
http://lpi.oregonstate.edu/infocente...nB6/index.html
This link provides alot of medical information about B6. It gives RDA recommendations, Toxicity warnings, and examples of food sources.

The University of Maryland has a great Alternative website, that cross references to drug use also.
http://www.umm.edu/altmed/articles/v...-b6-000337.htm

Vitamin B6 is really critical today. The lowering of homocysteine by conversion to SAM in the body is crucial for hundreds of chemical methylation reactions.
B6 works with B12 and folic acid to accomplish this.
So because of this focus, we hear more about B6 than we used to.
B6 is also used to prevent nausea in pregnancy. (the FDA approved its use a couple of years ago).

And B6 does so much, it is really very important to us. Over 100 drugs interfere with B6 in the body or deplete it.
Estrogens, many antibiotics, diuretics, INH, theophylline, penicillamine, Evista,
hydralazine are the families studied so far.

There has been an increased interest in a condition Pyroluria recently. This is a genetic trait that has an error in heme synthesis that creates a by-product called kryptopyrrole. While this is relatively harmless to the body, and is excreted in the urine, it complexes B6 and zinc while doing so and removes those nutrients from the body as well. We have an experienced poster who has done the testing here and I have invited her to come on this thread. Until then, the link below provides some information. I know there are others here, I just can't recall at this moment...so please feel free to post on this thread.
This can be tested using a urine sample, and requires a specialized laboratory to do it accurately. You can read more about that here:
http://www.pyroluriatesting.com/ This is the Pfeiffer Treatment Center

Vitamin B6 is a huge subject, so I will be adding to this thread as I gather data on various medical and alternative uses for it.

--just a question about the post--did you mean to put in a url link after the line "We have a long thread on Pyroluria here:" ? If you did, it didn't come up (at least for me).

I recalled that long thread by Ona...then after looking here, I realized it was
on "that other forum"... :o This happens when you get old you know...thoughts fly right out of your
brain sometimes and land somewhere else!

I'll edit the wording to reflect that.
I have asked a Pyroluria experienced person to come on...hope she does.

Pyridoxine B6 toxicity potential:

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]

mrsd, thank yo for this information. My PCP and I have been trying to understand why my B6 has been elevated.

I have discovered that even though my B12 is well within normal (last was over 700) I am functionally deficient in methyl-B12 as evidenced by lowering of my homocystiene levels to below high normal for the first time a week after starting sublingual methyl-B12 mega doses - this was a few weeks ago. I have developed a number of neurological symptoms, especially over the last year and a half that appeared to mimic MS. Many of those symptoms are improving now.

I guess its not such a far stretch of the imagination that my ability to covert B6 into P5P might be impaired as well.

This post is going to expand the P5P concept:

Today I am searching for more pyridoxal kinase problems. When I was first on the net 10 yrs + ago the data on pyridoxal kinase was just being released in some nutrition journals. Today there is much more available.

Here is an interesting 2007 paper that found that certain things in Gingko
block the actions of pyridoxal kinase:

Quote:

FEBS J. 2007 Feb;274(4):1036-45. Epub 2007 Jan 19.Click here to read Links
The human pyridoxal kinase, a plausible target for ginkgotoxin from Ginkgo biloba.
Kästner U, Hallmen C, Wiese M, Leistner E, Drewke C.

Institut für Pharmazeutische Biologie, Universität Bonn, Germany.

Ginkgotoxin (4'-O-methylpyridoxine) occurring in the seeds and leaves of Ginkgo biloba, is an antivitamin structurally related to vitamin B(6). Ingestion of ginkgotoxin triggers epileptic convulsions and other neuronal symptoms. Here we report on studies on the impact of B(6) antivitamins including ginkgotoxin on recombinant homogeneous human pyridoxal kinase (EC 2.7.1.35). It is shown that ginkgotoxin serves as an alternate substrate for this enzyme with a lower K(m) value than pyridoxal, pyridoxamine or pyridoxine. Thus, the presence of ginkgotoxin leads to temporarily reduced pyridoxal phosphate formation in vitro and possibly also in vivo. Our observations are discussed in light of Ginkgo medications used as nootropics.

PMID: 17250738 [PubMed - indexed for MEDLINE]

And here is a paper on racial differences in red blood cells and pyridoxal kinase:

Quote:

Haematologica. 2006 Jun;91(6):801-4. Epub 2006 May 16.Click here to read Links
The genetic basis of human erythrocyte pyridoxal kinase activity variation.
Flanagan JM, Beutler E.

Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.

Thirty years ago we reported that erythrocyte pyridoxal kinase activity of African-Americans was strikingly lower than that of persons with European ancestry in a tissue-specific manner. At the time, it was impossible to elucidate the mechanism by which evolution had selectively lowered the enzyme activity in one cell type but not in others. We have now identified a promoter mutation with potential erythroid-specific properties that could be the basis of a novel mechanism of controlling cell-specific decreased activity of an essential enzyme.

PMID: 16704963 [PubMed - indexed for MEDLINE]

I don't have access however to the whole paper, to understand the meaning of it.

This paper is from 1997...and mentions alcohol:

Quote:

Eur J Clin Nutr. 1997 Nov;51 Suppl 3:S39-45.Links
Dietary and other determinants of vitamin B6 parameters.
Brussaard JH, Löwik MR, van den Berg H, Brants HA, Bemelmans W.

TNO Nutrition and Food Research Institute, Zeist, The Netherlands.

OBJECTIVE: To assess the dietary, physical, biochemical and lifestyle determinants of vitamin B6 status parameters among healthy adults. DESIGN AND SUBJECTS: Dietary intake and status variables as well as other relevant characteristics were determined among 444 adults, aged 20-79 y and stratified for sex and 10-years age classes with a randomly selected control group (n = 300) and an over representation of persons with a low habitual vitamin B6 intake (n = 144). RESULTS AND CONCLUSIONS: The direct status parameters (plasma pyridoxal-5'-phosphate (PLP), plasma pyridoxal + PLP (PL + PLP), and 4-pyridoxic acid (4-PA) excretion) were clearly related to dietary variables and plasma concentrations of vitamin C (women only), vitamin B12 and folate. The total percentage of variance in p-PLP explained in multivariate regression analysis was 41 and 30% in men and women, respectively. The most important explaining variables besides vitamin B6 intakes were variables closely related to PLP-metabolism: albumin and alkaline phosphatase. Biochemical function related status parameters showed less statistically significant correlations with dietary variables. Four to 24% of the variance in the stimulation coefficients of erythrocyte aspartate aminotransferase (alpha-EAST) and erythrocyte alanine aminotransferase (alpha-EALT) and change in homocysteine excretion after a methionin load was explained by a combination of dietary, physiological and lifestyle related variables. The low percentages explained for some variables, notably alpha-EAST (women) and the change in homocysteine excretion after a methionin load (men), suggests that these parameters are not sensitive to the level of vitamin B6 intake as found in the present study. Alcohol contributed in many of the explaining models for vitamin B6 status parameters. Therefore, when assessing the vitamin B6 status of a population, it is important to estimate the level of alcohol intake as well. Furthermore, the results illustrate the importance of sex related differences in the metabolism of some parameters, especially homocysteine excretion. The variance in the clinical function related status parameter measured in the present study, handgripstrength, was explained for 50% by a combination of age, body weight and Quetelet Index (QI) with no important contribution of dietary variables.

PMID: 9598767 [PubMed - indexed for MEDLINE]

This is another version of that paper...

Quote:

1: Eur J Clin Nutr. 1997 Nov;51 Suppl 3:S32-8.Links
Micronutrient status, with special reference to vitamin B6.
Brussaard JH, Löwik MR, van den Berg H, Brants HA, Kistemaker C.

TNO Food and Nutrition Research Institute, Zeist, The Netherlands.

OBJECTIVE: To assess the adequacy of micronutrient status among the adult population, with special reference to vitamin B6 status. DESIGN AND SUBJECTS: Micronutrient status was assessed among a random sample of the adult Dutch population (reference group, n = 300), aged 20-79 y, stratified for age and gender, and among a group with a low vitamin B6 intake (n = 144). RESULTS: Low vitamin B6 groups had lower mean levels of erythrocyte and plasma pyridoxal (PL) and pyridoxal-5'-phosphate (PLP), urinary excretion of 4-pyridoxic acid, basal and stimulated erythrocyte aspartate aminotransferase (EAST) and erythrocyte alanine aminotransferase (EALT) activities and EAST stimulation coefficients but not of EALT stimulation coefficients, handgripstrength and 24 h homocysteine excretion before and after a methionin load test. Besides, plasma levels of vitamin C, B12 and folate were lower among low B6 than among reference groups indicating a combined low vitamin status. Direct biomarkers of vitamin B6 intake (plasma PLP and 4-pyridoxic acid excretion) were significantly related to more functional parameters (EAST, EALT and alpha-EAST). Among random reference groups the prevalence of plasma PLP values below 19 nmol/l was 3-7% for different age-gender groups, with the highest value of 16% among men aged 50-79 years. The prevalence of high values of erythrocyte glutathion reductase stimulation coefficient (alpha-EGR) and low levels of serum vitamin B12 and C was not more than 5% among different age-gender reference groups. CONCLUSIONS: Direct biomarkers of vitamin B6 intake confirmed the preselection of a group with a low vitamin B6 intake. The results suggest that the sensitivity of vitamin B6 status parameters for low vitamin B6 intake was highest for the direct vitamin B6 status parameters and lowest for handgripstrength and homocysteine excretion after a methionin load; results for enzyme stimulation coefficients were intermediate. The prevalence of below adequate status parameters for vitamin B2, B6, B12 and C was not more than 7% among the different age-gender groups, with the exception of a value of 16% for plasma PLP levels below 19 nmol/l among men aged 50-79.

PMID: 9598766 [PubMed - indexed for MEDLINE]

Zinc deficiency may impact B6 metabolism:

Quote:

Nutr Rev. 1990 Jun;48(6):255-8.Links
Zinc and the regulation of vitamin B6 metabolism.
[No authors listed]

Pyridoxal kinase, a key enzyme in the formation of vitamin B6 coenzymes, requires a zinc-ATP complex as a substrate. Recent findings show that zinc-metallothionein facilitates the formation of the zinc-ATP complex. Thus, the concentration of zinc-metallothionein in tissues may serve in the regulation of vitamin B6 metabolism.

PMID: 1365753 [PubMed - indexed for MEDLINE]

This is a huge article and note the date 1982:

Quote:

Q Rev Drug Metab Drug Interact. 1982;4(4):289-331.Links
Drug-pyridoxal phosphate interactions.
Ebadi M, Gessert CF, Al-Sayegh A.

In this review it has been pointed out that vitamin B6 and its vitamers can be involved in many interactions with a number of drugs, as well as with the actions of various endocrines and neurotransmitters. Nutritional deficiencies, especially of vitamins and proteins, can affect the manner in which drugs undergo biotransformation, and thereby may also modify the therapeutic efficacy of certain drugs. The differences between nutritional vitamin B6 deficiency and the hereditary disorder producing pyridoxine dependency are discussed. In addition to a pyridoxine deficiency being able to adversely affect drug actions, the improper supplementation with vitamin B6 can in some instances also adversely affect drug efficacy. A decrease by pyridoxine in the efficacy of levodopa used in the treatment of Parkinsonism is an example. The interrelationships and enzymatic interconversions among pyridoxine vitamers, both phosphorylated and non-phosphorylated, are briefly discussed, particularly regarding their pharmacokinetic properties. The ways in which the normal biochemical functions of vitamin B6 may be interfered with by various drugs are reviewed. (1) The chronic administration of isoniazid for the prevention or treatment of tuberculosis can produce peripheral neuropathy which can be prevented by the concurrent administration of pyridoxine. An acute toxic overdose of isoniazid causes generalized convulsions, and the intravenous administration of pyridoxine hydrochloride will prevent or stop these seizures. (2) The acute ingestion of excessive monosodium glutamate will, in some individuals, cause a group of symptoms including among others headache, weakness, stiffness, and heartburn, collectively known as the 'Chinese Restaurant Syndrome.' These symptoms can be prevented by prior supplementation with vitamin B6. The beneficial effect is ascribed to the correction of a deficiency in the activity of glutamic oxaloacetic transaminase, an enzyme that is dependent on pyridoxal phosphate. Some interesting relationships are pointed out between vitamin B6, picolinic acid, and zinc. It is postulated that the intestinal absorption of zinc is facilitated by picolinic acid, a metabolite of tryptophan. The derivation of picolinic acid from tryptophan depends on the action of the enzyme kynureninase, which is dependent on pyridoxal phosphate; therefore, the adequate absorption of zinc is indirectly dependent on an adequate supply of vitamin B6. The formation of pyridoxal phosphate, on the other hand, appears to be indirectly dependent on Zn2++ which activates pyridoxal kinase.(ABSTRACT TRUNCATED AT 400 WORDS)

PIP: This review examines the interaction of pyridoxal phosphate with select neuroendocrine and neuropharmacological systems and their health related therapeutic implications. Vitamin B6 and its vitamers can be involved in many interactions with a number of drugs as well as the actions of various endocrines and neurotransmitters. Nutritional deficiencies, particularly of vitamins and proteins, can affect the manner in which drugs undergo biotransformation and thus may modify the therapeutic efficacy of certain drugs. In addition to pyridoxine deficiency adversely affecting drug actions, improper supplementation with viatmin B6 can in some instances also adversely affect drug efficacy. A decrease by pyridocxine in the efficacy of levodopa used in the treatment of Parkinsonism is an example. The interrelationships and enzymatic interconversions amony pyridoxine vitamers, both phosphorylated and nonphosphorylated, are briefly discussed, particularly concerning their pharmacokinetic properties. The chronic administration of isoniazid for the prevention or treatment of tuberculosis can produce peripheral neuropathy which can be prevented by the concurrent administration of pyridoxine. An acute toxic overdose of isoniazid causes generalized convulsions, and the intravenous administration of pryidoxine hydrochloride prevents or stops these seizures. The acute ingestion of excessive monosodium glutamate will, in some persons, cause a group of symptoms, including headache, weakness, stiffness, and heartburn, collectively known as the "Chinese Restaurant Syndrome." These symptoms can be prevented by prior supplementation with vitamin B6. It is postulated that the intestinal absorption of zinc is facilitated by picolinic acid, a metabolite of tryptophan. The derivation of picolinic acid from tryptophan depends on the action of the enzyme kynureninase, which is dependent on pyridoxal phosphate. Therefore, the adequate absorption of zinc is indirectly dependent on an adequate supply of vitamin B6. The formation of pyridoxal phospate appears to be indirectly dependent on Zn2++ which activates pyridoxal kinase. Treatment with daily pyridoxine can reverse a state of depression induced in women who take oral contraceptives (OCs). 1 hypothesis to explain this effect is that the OC is somehow causing a deficiency of seroton serotonin in the brain and that the vitamin B6 helps to overcome this deficiency through the stimulation of 5-hydroxytryptophan decarboxylase by pyridoxal phosphate. In sum, the stimulation of 5-hydroxytryptophan decarboxylase by pyridoxal phosphate. In sum, pyridoxal phosphate in physiological concentrations seems to function as an endogenous "down regulator" of several receptor sites, including estrogen, progesterone, and androgen.

PMID: 6087425 [PubMed - indexed for MEDLINE]

Dear MrsD.

How would you feel about publishing a book entitled, "Vitamin b6 for dummies"?

I'm lost.

I suppose being six weeks into another neuro flare and loaded for bear with baclofen doesn't help my wee little brain.
But a gigantic THANK YOU to you for your helpful post and info.

b12 started @ 220 now up to 668! after nearly 2 years (big whup.)
b6- 92 ?!?!? what in the world- I don't even take vitamins but occassionally!

neuro is going to test zinc in this boat load of blood work.....he suspects my kidney issues to be partly the culprit..........I/he has no idea where to look for info, he's been asking around in his circles and no one knows anything about it.

This is a huge help, I can email my neuro with a the info you posted.

thanks so much!
lah

ps. Hi therese

Lah,

Sorry if we've already done this, but what type of B12 and how much have you been taking these two years?

rose

With all the questions on other forums here about antidepressants, I thought it would be helpful to bump up this post, since B6 is so important to serotonin synthesis...

Thanks Mrsd..I did not know about the connection to serotonin. :hug:

:bump: bumping this thread up for new posters....

General comment and question...

A few years ago, my doctor suggested I take a B50 tablet and extra B12. He did this after taking a test for B12 and doing other lab work. Later, he increased the B12 to a very high dosage. The B50 tablet has a variety of B vitamins in it; including 50 mgs. of B6 in it. It has improved my energy level and folks were so impressed by this...they went out and bought some B50 for themselves!

Dream Recall
I have heard that the B vitamins, perhaps B6 in particular, influence dream recall. I once experiment with taking a B75 and it did seem that I had more dream recall. However, I cut back down to the B50 again because I was concerned about taking too much of the B6. Does anyone know if the B vitamins influence dream recall? What is this all about?

Thank you.

Quote:

Originally Posted by Vowel Lady (Post 282405)

Yes, B6 influences dream recall. One sign of pyroluria, which creates a deficiency of B6 and zinc, is inability to recall dreams.

B6 is needed to make serotonin, which then is used to make melatonin.
MethylB12 is used in this conversion to melatonin. Melatonin is the natural sleep hormone, and necessary for all the sleep stages to work properly.
REM is one sleep stage.

This site has some other ideas too.
http://www.buynytex.com/vitamins.html

bumping up while I am on vacation.

For those with good insurance. Metanx is a prescription Vitamin B supplement with methylated B12, Methylated Folate, and P-5-P. I have a good link, but apparently I am not yet allowed to put links in my posts.

I'll put it up...

I've recommended Metanx for a long time now. It is RX only, and some insurances do not pay for it still. I've posted it many times here.

I have noticed the website is different now. Not sure what that means.

http://www.metanx.com/

I find it interesting that all 3 activated B's are in it. I see this as a good sign for patients.

There is another RX vitamin called Cerefolin.
http://www.pamlab.com/Products,Cerefolin
This has P5P removed, and NAC -- n-acetyl cysteine added.
The NAC is to promote synthesis of glutathione.

There are studies showing methylcobalamin is very helpful to prevent neuro degeneration and neuropathies.

Quote:

Originally Posted by mrsd (Post 388933)

I have noticed the website is different now. Not sure what that means.

I find it interesting that all 3 activated B's are in it. I see this as a good sign for patients.

There are studies showing methylcobalamin is very helpful to prevent neuro degeneration and neuropathies.

I find it fascinating that these vitamins help some people with symptoms of "schizophrenia". Me thinks that should be called symptoms of needing B vitamins instead of symptoms of "schizophrenia".

As for the new look of the website.... :mad: I cannot find the "Unaffected by the MTHFR polymorphism page which was EXCELLENT. The link had been: metanx.com/UnaffectedByTheCTPolymorphism which no longer works.

It showed the cycle using the vitamins. Maybe too many people were hitting the website just for that page?

I tried this and got some burning symptoms. I thought maybe it was the amount or ratio of folic acid in it for me.

So I combine them separately with the folic acid at a much lower level and am fine.

Life Extension has this: Pyridoxamine/B6/50 mg.
However, their B complex has something else for B6. This is causing a dilemma for me, since I don't really want to give up my B Complex (I take additional B12 along with it).
http://search.lef.org/cgi-src-bin/Ms...6&hiword=B6%20

if it works for you

don't change. P5P is basically for people with failures in B6 metabolism. Since this has been a hidden issue, it is recommended for people with neuro problems (who may have metabolic failures and that is why they have neuro issues).

But if your product works for you, then you obviously don't need to change.

Nice to see you are back and safely too.

bumping with new information..

New studies show using high dose B6, B12, and Folate, reduces
macular degeneration. This study followed 5000 women for 7 years!

http://www.sciencenews.org/view/gene...protect_vision

Quote:

After 7.3 years of follow-up, those reports had turned up 82 cases of age-related macular degeneration among women taking placebos and only 55 cases in the women getting the vitamin supplements.

While an explanation for the apparent protection from macular degeneration remains unknown, it is known that folate, B-6 and B-12 can drive down blood concentrations of homocysteine, a compound suspected of damaging blood vessels. Researchers have tried to finger homocysteine in heart disease, but studies have failed to show a heart benefit from reducing homocysteine levels.

It is something to think about.

Sorry about the repetitive nature of this post, but it was noticeable for me how much improvement I felt in my energy levels when I started to take a B50 tablet and a B12 tablet (methyl type) regularly. Few of my vitamins have brought me this much noticeable difference. These are two tablets I make sure to never forget to take. I strongly believe in the power of the B vitamins and recommend them to everyone. Many of my friends are taking them now...including a friend in the medical field who took the time to do her own research and is now a big fan!

A moderate to severe risk for someone with CMT if taking high doses of B6:(

Quote:

Originally Posted by Kitt (Post 472041)

A moderate to severe risk for someone with CMT if taking high doses of B6:(

Depends on what is "high" to you. I doubt they took more than 50mg a day.

What dose do CMT patients find harmful?

It is not what is "high" to me. It is what the experts on CMT recommend. I should have said "mega dose" instead of "high". Sorry for that. I am specifically talking about CMT.

However, a mega dose of Vitamin B6 is 10 x the RDA allowance which is 20 mg. A neurologist who is an expert in CMT prefers no more than 10 mg daily. It can damage nerves in people who have CMT. There also can be other side effects. This allowance would include the foods you eat, drink, or supplements in the equation.

Obviously some people with CMT can get by with more depending where they are as far as CMT is concerned. None of us CMTers are the same. CMT varies greatly even within the same family. However, the recommendation is for anyone who has CMT whatever stage they are in or not. There are many types of CMT.

I only posted this so that a person with CMT who might be reading this would be aware. There is a medical alert list of many drugs that people with CMT should be aware of. We do not have the same peripheral neuropathy and other problems, that other people have.

I found this list:

http://www.charcot-marie-tooth.org/med_alert.php

I think "mega" implies the 500mg that was commonly used in the past daily...for PMS and other maladies.

I wouldn't call 50mg a day "mega".

In fact the FDA has approved pyridoxine for pregnant women who have alot of vomiting issues. That dose is 75mg a day.
Metanx has 25mg of P5P (activated pyridoxine) in it. This would be easily equivalent to 50mg of pyridoxine (which is not activated). So it brings to mind the question... is the unactivated form that bothers CMT patients, or the P5P form?
From what I have gathered over the years, the P5P form is safer in people with special needs/problems. The "toxicity" of pyridoxine was only measured with the unactivated form, and is thought to pertain to IT only.

I also found it interesting that fluoroquinolones were classed as
minor. I think these drugs cause PN in many normal people!
They have become a real problem. I think they should be moved up the list.

Thanks for bringing it up, Kitt.

CMTers should go

by what the experts in CMT say. 50 mg is called a mega dose for people with CMT. It certainly is not a mega dose for the general population. I agree with that. I certainly will not jeopardize my PN with more than is called for.

What the FDA has approved for pregnant women who have a lot of vomiting is quite another matter. A pregnant woman with CMT should go by what the experts in CMT say. And, as mentioned before, there are many drugs, etc. that a person with CMT must be aware of. They should work closely with their neurologist/doctor who does know CMT.

As far as the general population, that is another matter. And, yes, the site you refer to is the Medical Alert list for people with CMT.

Apparently the experts have done their research concerning Floroquinolones for people with CMT and they are considered negliable or doubtful for people with CMT. They came to this conclusion thru their research and studies of people with CMT. The list does change now and then as to where the experts findings take them. Again, the list is for people with CMT.

For the most part CMT is an "inherited" peripheral neuropathy. There are 22+ types of CMT that they now can do DNA blood testing for. There are many kinds of CMT and there are about 50 types identified so far and there is no end in sight.

Thank you mrsD for your post.

mrs d......have a patient in ltc, that has elevated B6....on no sup...hx of etoh abuse....female......would a zinc sup, and p5p be the way to go? her doc appears to be open to some nutritional suggestions....patient def has mood issues.....and has been dx with dementia......

If B6 is building up in the blood, this indicates to me that your patient is not converting it to the active form.

There are studies that autistic patients have elevated B6 this way too, with no history of vitamin supplement intake.

B2 Riboflavin is the cofactor in the enzyme pyridoxal kinase. If B2 is lacking, pyridoxal cannot be made from pyridoxine.

This enzyme is also affected by some drugs. Theophylline is one.
I have also read that "amine" drugs also affect this enzyme.
Here is one study:
http://www.sciencedirect.com/science...5eda525e449a6e

Quote:

Depending on the results, the inhibiting drugs were divided into three groups. The first group included theophylline and progabide and inhibited PLK using either PL or pyridoxamine (PM) as substrate and thereby were true inhibitors. Moreover, they did not form covalent complexes with PL or PLP. The second group, which included cycloserine, dopamine, isoniazid, and thiamphenicol glycinate, inhibited PLK using PL, but not PM, as substrate. They were able to react with PL or PLP to form covalent complexes, and kinetic studies suggested that the observed PLK inhibition was due to these formed complexes. A third group, which consisted of levodopa, D-penicillamine, and muzolimine, inhibited PLK using PL, but not PM, as substrate.

I think the jury is still out on other drugs at this time.

This paper discusses testing the enzyme, and lists nicotine and
theobromine as inhibitors, as well as a cousin of theophylline.
http://74.125.95.132/search?q=cache:...&ct=clnk&gl=us

thanks,...i thought i had read in some of the previous that zinc , and for woman-vit C, were also important? but i missed the B2.....and with the etoh background.....i think she is alreay on thiamine......

B2 is riboflavin, not thiamine. Thiamine is B1. But if she is an alcoholic, doctors typically put them on Cefol, or something like it. (which would be B-complex and would have both in it).

Quote:

Originally Posted by mrsD (Post 578903)

B2 is riboflavin, not thiamine. Thiamine is B1. But if she is an alcoholic, doctors typically put them on Cefol, or something like it. (which would be B-complex and would have both in it).

lol....I KNOW that b2 isnt thiamine.....i was referencing the thiamine to the etoh.......

Quote:

Originally Posted by mrsD (Post 392469)

Hi. This is my first time here. I have been in emergency twice this week (only once before in my 40 years). I thought I was having a stroke because of tingling in my leg in the am, arm in the pm, and face the next day, my daughter's 10th birthday!:( The tingling in my leg has since subsided. They ruled out stroke. My strength and coordination are good. I did start taking a
B6, B12, Folic Acid formula 3 days prior to the onset of these symptoms. The amount of B6 is 50mg. The only other vitamin I have ever taken was a One-a-Day, which apparently has 1/20 the amount of B6. Dr.s are telling me B6 levels cannot be tested for with a blood test. I am scrambling, trying to figure out what is going on. I do not take any other drugs, and the only health problem I have is an underactive thyroid. I am on Synthroid for this.
Thank you.

It is hard to say without testing.

Bcomplex could be increasing healing in previously damaged areas, and tingling is a sign of nerves waking up (or dying).

The fact that B6 causes neuropathy at BOTH ends of its spectrum --too low and too high--- makes diagnosis difficult when symptoms appear.

Thyroid can cause weird sensations, and so can perturbations in calcium/magnesium status.

There are definitely blood tests for D,K, B12, B6, thiamine, folate.
There are also tests for red blood cell content of vitamins instead of serum which most doctors order. Spectracell labs do these.

http://www.spectracell.com/

I found this article this morning...it is very interesting:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1297572/

Quote:

Vitamin B6 deficiency results in adverse health consequences, including hyperhomocysteinemia [1] and possibly arteriosclerotic lesions [2]. We have reported that the degree of disease activity is associated with vitamin B6 indices in patients with rheumatoid arthritis [3,4]. Bates and colleagues reported suboptimal vitamin B6 status in inflammatory conditions and in the acute-phase response in the elderly population [5]. These observations have attracted attention partly because vitamin B6 deficiency and several markers of inflammation were both found to be independent risk factors for thrombosis [6,7]. Although several clinical trials and epidemiological studies have demonstrated the associations between vitamin B6 and inflammatory diseases, the association between vitamin B6 status and inflammatory markers has been contentious, and the cause-effect relationship between these two has not been elucidated....
Results:
In the human study, plasma pyridoxal 5'-phosphate concentrations were significantly lower in patients than in healthy subjects (with about 50% lower). This observation was comparable to our previous finding [3]. In contrast, no difference was found between patients and controls in erythrocyte pyridoxal 5'-phosphate or erythrocyte aspartate aminotransferase or 4-pyridoxic acid levels. No difference was found in concentrations of plasma folate, red blood cell folate or plasma vitamin B12 between patients and controls.

B6 and Parkinson's

This link is thanks to lurkingforacure at Parkinson's forum:

http://www.sciencedaily.com/releases...0115182627.htm

It concerns the poor expression of pyridoxal kinase in the brain being linked to a faulty gene which occurs in Parkinson's patients.
Pyridoxal kinase is the enzyme that activates pyridoxine from food and supplements so the body can use it.

I have advancing neuropathy for years, getting problems with walking. Now I read that to much B6 can be the problem. I take 10 mg B6 a day, but my bloodlevel is 536 nmol/l, which is quite high. Pyridoxal is 137 nmol/l. I don't know about pyridoxal bloodlevels, is this I high level? Or could it be that I don't make pyridoxal from pyridoxine? If so: what to do? If not: where does all the B6 come from.

I am Dutch and I find it quite difficult to write in English as you probabely notice. But I can read it really well...

This subject keeps cropping up for patients with PN.

First of all regarding blood levels:

I don't think the medical community can interpret these except for very low ones. The reason is that lab ranges are determined from a statistical comparison of so called normal people who have their blood drawn (who have no pathology that is known at the time). Higher than those ranges would be found in anyone who takes any supplements. For example for B12, people taking a supplement often report out of range values, 1000-2000, when 800 is typically the upper cut off. These high values of B12 only show that it is being absorbed into the body as needed. The tests for B6 are most accurate in the very low ranges, and were initially designed to discover patients suffering from drug induced low B6--- some drugs cause this, like INH which is used to treat tuberculosis.

Pyridoxine has the confusing issue of causing neuropathic symptoms in very high doses, and when deficient, so this clouds the interpretation of blood values also. We are finding --as per the study I quoted earlier in this thread--- that autistic children present with high blood levels --higher than expected--- when there are NO supplements being used. This reflects a genetic error of metabolism of some sort, which has not been explained as yet. But in the face of these results, doctors for autistic children give MORE B6, and it helps.

The only documented studies I have seen on PubMed involve giving GRAMS (1-3 grams) of B6 which were seen to cause neuropathic toxic symptoms. The actual number of people who have been reported to have toxicity from B6 is very small.
This became evident back in the days that B6 was used in very high amounts of 500mg a day or more for treating PMS in women.

Why B6 is building up in some people, is still unknown. Why it is not excreted as a water soluble vitamin is also unknown. But we do know that B6 as pyridoxal is stored for short periods of time in muscle tissue to aid in metabolism and creation of energy. There is B6 in the food you eat. Mostly from meat.
Some fortified cereals contain about 2mg of B6 (Total for example) per serving, and some grains like wheat.

I don't think at this time there is an answer to your question. I could not find any explanation for a small daily intake of B6 to cause your problems. The only way for you to find out what is going on is to stop all B6, stop eating fortified foods, and cut back on meat for a while --6mons or longer-- and see what happens. If you have no intake of B6 you should not have high blood levels. If your levels go down and you still have neuropathic symptoms, then the B6 is not your culprit. All the studies show that ELEVATED B6 neuropathy is reversible, and not permanent.

The medical community is finding that genetic errors of metabolism in humans occur, and they may account for age acquired chronic diseases.

There are people born with a condition called B6 dependency.
These individuals typically have seizures beginning in infancy, and require huge amounts of B6 to stop them. They take doses that are enormous, and they do not develop neuropathy. But they are also rare, and I saw a quote once that only about 100 people have been identified with this disorder.
http://emedicine.medscape.com/article/985667-overview

People may not convert pyridoxine to pyridoxal if they are low in riboflavin-- B2.

Progressing neuropathy can have many causes. Autoimmune, gluten intolerance, hereditary Charcot Marie Tooth genetic errors, insulin resistance/diabetes, thyroid disease, certain drugs like statins and fluoroquinolone antibiotics, and some chronic exposure to toxins in the environment.

when/how to take NOW p5p?

I just bought NOW enteric coated P5P 50 mg. The instructions say to take it before a meal, but I find it hard to follow that for my teenage son with tics during the school week. Within 10 minutes of waking up for school, he's ready for breakfast. As soon as he comes home, he's ready to eat...and I would be nuts to think he would wake up earlier to swallow a pill. I might be able to give it to him in the evenings, but again, it seems like he's snacking after dinner till bedtime.

How bad is it to take P5P with food?

This is what I give my son.

15 minutes after waking up (with breakfast):
1 tsp natural calm
1/4 tsp NOW taurine powder 1000mg (just started today)
1/4 tsp Jarrows inositol powder (may discontinue when I run out)
1 capsule CVR magnesium taurate
1/4 tablet Natrol 5htp (25mg 12 hour release)
1/4 cup raw and roasted shelled pumpkin seeds from trader joes for mag.
1 gummy multi vitamin and gummy omega
1 p5p (haven't started this yet-hope to boost the magnesium effectiveness)

Evenings:
1 tsp natural calm
gummy omega
1/4 tablet 5htp
more pumpkin seeds

Our hope is to alleviate the tics during 8am-4pm, when he's at school. He doesn't tic much when he's at home.

Should he take more supplements in the evening, in hopes that it gets absorbed and works then during 8-4pm. Or is it best to give to him at 7am?

I was hoping to split the P5P am/pm, but with the enteric coating, I thought that would defeat the purpose.

My son doesn't even know that I put the 3 powders in his OJ in the mornings. He is willing to take some supplements and eat pumpkin seeds to reduce his tics, but still laments about taking "pills like an old man". He was on vitamin shoppe mag citrate for a while, but I had to cut the pills into 3, so switched to the Calm and Mag Taurate recently.

I would love feedback on how to best give the supplements for optimal absorption and effectiveness during the school hours.

I'm considering stopping the 5htp and trying SAM-e 200mg. My son isn't outright depressed, but he's a quiet kid and doesn't display much enthusiasm/happiness. When he saw the bottle of 5htp for "mood enhancement", he was very willing to take it, so I know he considers himself a bit down too. But I read SAM-e also needs to be taken on an empty stomach, so that may be an issue too.

I could give him the P5P on weekends before breakfast, and maybe again just on Wednesday. Does P5P stay in your body, or does it flush out? Sorry I'm just thinking outload.

Thanks so much for any help and advice.