The new scientific opinion (EFSA) revised in Europe the Tolerable Upper Intake Level (UL) for vitamin B6 of 12.5 mg/day for adults (including pregnant and lactating women), down from the previous UL of 30 mg/day set in 2000. For infants and children the ULs are: 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). Excessive intakes are associated with peripheral neuropathy, a type of damage to nerves in the body’s extremities. Based on available intake data, EU populations are unlikely to exceed the ULs, except for regular users of food supplements containing high doses of vitamin B6.
Scientific opinion on the tolerable upper... - Cure Parkinson's
Scientific opinion on the tolerable upper intake level for vitamin B6
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Yet again, there appears to be no distinction in this meta analysis between vitamers. If no-one ever inquires which form of B6 is being taken, which they certainly haven't recorded in my own case, and it is rarely tested either, how will the data ever be of use? Have a look at pubmed.ncbi.nlm.nih.gov/287...
Fortunately for me I was already taking P5P and shall continue to do so. Low B6 can also cause neuropathy. Cheers
The very extensive EFSA study as the basis for the new guidelines does also discuss P5P (PLP) in the toxicity of B6. (3.5.1.3. Mechanisms of toxicity). The Dutch researchers you mentioned Hadtstein and Vrolijk recently (2021) reviewed four prevailing theories on the potential mechanisms by which high intakes of vitamin B6 could cause peripheral neuropathy. It confirmed my experience that P5P may not be as innocent as initially thought. In addition to a severe B6 deficiency, a later overdose of P5P has indeed influenced my peripheral neuropathy. There is no definitive answer about how the complexity of the many components of B6, including P5P, ensure the toxicity of B6. However, it makes no sense (and apparently that can even lead to shortages!) To supplement unnecessary high doses of B6. Normally good nutrition is sufficient, but probably due to the interaction with C/L medication in PD, I need about 5 mg extra B6 per day. That's about 20% of the amount of carbidopa intake. I also stick to P5P, but regular testing of my B6 level remains necessary!
Here is a quote from the study “Vitamin B-6-Induced Neuropathy: Exploring the Mechanisms of Pyridoxine Toxicity” with the latest insights:
“In order to better characterize the safety profile of PN supplementation, the mechanism of toxicity has to be clarified. Despite a long history of study, the pathogenic mechanisms associated with PN toxicity remain elusive and there is even a lack of consensus over which vitamin B-6 vitamer leads to neuropathy. Several competing theories have been proposed to explain its mechanism of action. These include aldehyde toxicity through elevated pyridoxal 5′-phosphate (PLP) concentrations, the formation of reactive quinone methide-type intermediates, the competitive inhibition of PLP-dependent enzymes, and the saturation of pyridoxal kinase (PDXK) (4, 16., 17., 18., 19.). Many aspects of the proposed hypotheses are unexplored, and even the basic assumptions they are grounded in can be contested, particularly concerning PN pharmacokinetics, toxicological testing, and vitamin B-6 metabolism. Therefore, the present review is focused on investigating the mechanistic link between PN supplementation and sensory peripheral neuropathy.”
sciencedirect.com/science/a...
Normally good nutrition is NOT sufficient for those taking levodopa medication. B6 deficiency is commonplace in such PWP: Vitamin B6 Deficiency in Patients With Parkinson Disease Treated With Levodopa/Carbidopa pubmed.ncbi.nlm.nih.gov/329... "All patients treated with intraduodenal L-DOPA/CD (6 of 6) and 13 of 18 patients receiving L-DOPA/CD orally had low plasma levels of vitamin B6. Eight of the 19 patients with low vitamin B6 levels had symptoms of hypovitaminosis B6."
B6 deficiency can be disastrous - convulsions due to no B6 left: Refractory Seizures Secondary to Vitamin B6 Deficiency in Parkinson Disease: The Role of Carbidopa-Levodopa karger.com/crn/article/14/2...
On first reading of the Vrolijk 2021 paper the toxicity of pyridoxine is made quite clear. The potential toxicity of P5P is speculative, and we have this: "injections with high doses of PLP [alternate name for P5P] in rats failed to induce the morphological changes associated with PN-induced neuropathy "
It is not only the interaction with carbidopa, but B6 deficiency is already present in some at an earlier stage of PD and the C/L medication. Peripheral neuropathy arose in me before diagnosis, as was later evident due to a severe B6 deficiency. So you don't have to tell me that a B6 deficit can be disastrous. But since my first HU post from a year ago, I've been advocating: let everyone with PD test their B6 level first. However, recommending vitamin B6 in advance seems unwise to me. The eagerness with which supplements are taken in the PD community carries the risk of overdose, with or without P5P, with all possible consequences. At first, the Vrolijk and EFSA recommendations do indeed apply to pyridoxine, but the complexity of B6 as they indicate does not exclude other culprits. So just don't take unnecessary risks and test regularly!
Like Park Bear, I'd think more don't have good absorption than do, so good nutrition is not enough at all. I don't have PD but do have B vitamin difficulties. Doctors can't reliably pick up a B12 deficiency and generally mis-prescribe for folate deficiencies so hardly surprising that B6 gets little attention. So many possible contributing factors to neuropathy which don't get properly looked for and could be confounding the B6 'effect'. Of course testing is a good idea, if it is available and accurate. I don't know if it is for B6, but it isn't for B12. Cheers
Testing is the only way to get an idea of what's going on. Even if the test were not very precise, I don't have that impression, it can still help to balance. Of course there are many other possible causes as my neurologist claimed at the time, but by not directly investigating the B6 problem common in PD by a simple test, a year has been lost and for a probably irreparable neuropathy as bonus.
I agree and I do appreciate where you are coming from. I was misdiagnosed 23 years ago so also have irreparable neurological issues, although I am working on all possible causes and treating as required to support those found. But I wonder how many with PD (and all other) neuropathy also have a B12 metabolism problem which has not been picked up due to lack of testing and flaws with testing process. B12 deficiency is also very common. (Low levels of B12 have been associated with peripheral neuropathy, cognitive impairment, and more rapid rate of disease progression in Parkinson's according to parkinsonscare.org.uk/vitam.... Best wishes
remember the medication destroys b6 so I don’t think it would have the opportunity to accumulate?
That depends on the degree of supplementation with B6 and of course the amount of C/L medication. The initial advice to take at least as much B6 as you take on carbidopa has at least caused me a significant overdose. After some adjustments, as mentioned, I am now at 20% of the amount of carbidopa, about 5 mg per day. That will be different for everyone. Measuring alone is knowing.
interesting the side effect didn’t seem to vary much by dose. Makes you wonder if it was something else causing the symptoms like eg shortage of eg b12 or magnesium.
B6
That is what you want to read and start drawing your own conclusions from a small part of the data. There is a 110-page report from specialized scientists and data from many countries. Fine if people just want to take their multivitamins with too high a dose of B6 pyridoxine, but I advise everyone to follow EFSA's advice. However, with the caveat that this maximum dosage may have to be increased if it turns out, only after testing, that there is still a deficiency due to the influence of the Carbidopa. Don't take risks. Peripheral neuropathy is really a big problem with PD often caused by B6 deficiency and overdose!
Ok
Another addition. Also remember that an excess of B6 can also break down the carbidopa of the PD medication, making your C/L less effective. 🍀
I feel like b6 is more critical to the body than carbidopa to be honest.
ok, so now i am totally confused. my 7/13/23 B6 results were at low end (3.0) but still considered normal (2.1 - 21.7)by blood lab range.On 7/27/23, i started taking P50P (no c/l) 2 hrs before or 2 hours after taking B6 ), and I still have slight peripheral neuropathy in my 2nd and 3rd toe of left foot and PD symtoms are still raging) . Left side is my weak PD side. I will be getting another blood draw in a week or so. based on this latest post, it seems to indicate eithrt too much B6 or too little B6 can cause neuropathy. Am I reading this right?
You are right, but do not expect a quick result from supplementation with B6. With me at the time (and still today) spectacular for improving my PD, but not for my peripheral neuropathy. I have the idea that after a year the PN may have become a little less, but it can also just be a habituation to the burning pain. The damage to the nerve pathways will be re-examined next week.
Maybe it’s time you look for solutions for this ailment - Neuropathic Pain - outside the B6 arena.
See chartist suggestions here -
healthunlocked.com/cure-par...
Missing from that list is Acetyl-L-carnitine (ALCAR) which some claim enhances nerve regeneration. It is a dynamic partner to Alpha-Lipoic Acid which alleviates neuropathic pain
See here also
ncbi.nlm.nih.gov/pmc/articl...
trialsjournal.biomedcentral....
Wishing you the best 🌹
Thank you for thinking along. The most important thing is still to ensure that the PN does not deteriorate and if possible, against the expectations of the doctors, to work on a recovery. The fact that the particularly low B6 level plays an important role in both my PD and PN is my top priority here. In addition, Art's PN advices are certainly important to achieve an improvement, just like with the PD. That seems like a big challenge, because according even the HU Neuropathy Support members there is just nothing to be done about it. Everyone is only talking about the pain relief. That was also said with the PD diagnosis, but I do not accept this resignation that also entails so much pain and immobility by loss of muscle strength. So thanks for your concern, I'll keep searching. Interesting is the research on propionate that was brought to the attention by Ethin. I am now one of the guinea pigs.
I have carried out B6 test and it is 108 ng/mL. I only take B complex having B6 quantity of 100 mg. Can 108 ng/ml cause toxicity ?
Healthy human blood levels of pyridoxine are 2.1 - 21.7 ng/mL
I think it would be wise to stay within that margin. You have an extremely high value and it will probably take up to 2 months with B6 fasting before you return to a 'normal' level.
100 mg B6 in your B-complex, perhaps even not P5P, is really way too much and a great risk of developing peripheral Neuropathy and impact on your possible C/L medication.
Very nice that you share this with us. It provides insight into what the influence of your supplementation can be on your B6 level. What is your daily carbidopa intake and how long you use this or other B6 supplements? I hope more members follow your example! 🍀
for the last year or so I have noticed a faster progression of the symptoms coupled with the increased weakness in hands and feet. I suspect these are the effects of peripheral neuropathy. I was unable to pinpoint the cause of sudden deterioration of symptoms. B6 toxicity may be the culprit
That seems very likely to me... If it is indeed the case, it will probably take a while before you experience the effect for your PD and perhaps neuropathy of stopping B6 through the long half-life. Good luck and please keep us informed!
I have more or less the same suspicion after checking the dates of the first intake of b6.
My recent b6 test gives a value of 97.7 out of a maximum of 18 to be normal and after a month without vitamin B6 I feel little better.
Vitamin B6 binds to the blood and has a half-life of approximately one month.
my doctor recommends two months of supplementation and two months off if one needs it.
I think I will take a B complex with very little vitamin B6 max 10 mg.
Ha Gio, didn't you have an estimated B6 supplementation of about 7mg per day? Given the serious overdose and problems that that brought, I would choose to take a B- complex with very low B6 dosage of 2 to 4 mg. Difficult to find but they exist. Otherwise a B- complex without B6 and supplement with the non-toxic P5P. Try to find balance in your B6 by testing every now and then instead of 2 months nothing and 2 months too much. Most neurologists are aware of the danger of the risk of too high a B6 dose, but do not know what to prescribe to B6. Just to be sure, they say it's better not to take supplementation for only 2 months
Blood tests: How long should you fast from b vitamins before blood work? Should you also try to eliminate it from your diet for a few days?
I wouldn't fast with your B vitamins for a blood test if you wanted to have a realistic image of your current situation. After even a day of fasting, the B values are much lower. Only at the B12 where the half-life is a week and at B6 a month, the values fall very slowly.
To know how your B6 values are without supplementation you have to fast B6 for at least 3 to 4 months.
The advice I was given was not to take the b-complex the same day as the test. I gave it four days the last time I tested. But I only take one b-complex every 3-4 days. My b-complex has 10mg of p5p.
Julie, if you want an average situation of the effect of your B complex I would do a test halfway, so after 2 days.
following document shows that in some individuals even a smaller dose taken for a shorter duration can cause the toxicity.
downloads.regulations.gov/F...
Thanks for the warning. If you see how much B6 is in the Multivitamins and B-complex recommended here I'm shocked. Remember that normally 1.5 mg through your food is enough. Why on earth would you want to take more vitamin B6 when your values are good, with the risk of very harmful side effects as neuropathy.
Despite the fact that I probably have to take B6 supplement due to the C/L medication, I still have an overdose at 12.5 mg a day. That's why I'm actually at 3 mg a day. Do you now understand that I keep calling for your B6 to be tested?
I've updated my posts to recommend B6 testing.
I'm happy with that! 🙏
It remains that we have other experiences with the desired supplementation with B6 with C/L medication. This is the interaction with carbidopa where you propose to keep the B6 supplementation equal to the daily intake of carbidopa. For me, this has led to an overdose after a severe B6 deficiency, both are not desirable given the functioning of levodopa and for me also the problems with peripheral neuropathy.
You could be right in principle, but shouldn't you take into account the half-lives of carbidopa and B6? From carbidopa this would be 107 minutes according to my information. However, at B6 between 25 and 32 days (!) About 400 times as much. This is much more than the 55 hours Frank Church made his stacking chart with. journeywithparkinsons.com/2...b-vitamins-folate-b6-b12-reduce-homocysteine-levels-produced-by-carbidopalevodopa-therapy/
In any case, B6 remains present in the body much longer, while the carbidopa is metabolised and excreted faster. Suppose the interaction between B6 and carbidopa is equivalent and there are no other factors affecting this process (I don't think we know that), I used AI to calculate what amount of B6 is needed daily when taking 100 mg carbidopa. That turns out to be about 20 gr.,… 🤔 So again AI proves to have problems with calculations. The search for a reliable recommendation continues.
Yes I'd like to find a rule of thumb of taking B6 at some proportion of carbidopa consumption that we can agree on. The lengthy half life that you cite presumably was derived using healthy people. In healthy people the body recycles B6 from the inactive to the active form so it only needs to be replenished at a very slow rate. In Parkinson's patients taking carbidopa this no longer applies because carbidopa inactivates B6 and thereby renders it unable to be recycled. So taking B6 at some proportion of carbidopa consumption makes perfect sense. Unfortunately I could find no information in the medical literature regarding the rate at which carbidopa consumes B6.
Regarding the above calculations, for item number three, to maintain balance, the daily supplementation of B6 should be equal to the amount consumed by carbidopa plus an additional safety margin. Item number five is not a correct means of calculating the B6 dosage. In addition, 50 mg * 404.68 = 20.234 grams.
AI large language models are merely computer programs that put together likely combinations of words. They cannot create valid new facts where such facts are not already in existence. Nor can they be expected to do mathematics. They are good at writing essays but only if such essays are subsequently fact checked by humans.
Indeed, AI's calculation is completely wrong. The result does not appear to be 20 mg but 20 gr of B6. 😅
Still, it does not seem unwise to take the average carbidopa value over the day. For an intake of 100 mg, this will be about half the value, i.e. 50 mg. This is then offset by 50 mg of B6, which hardly breaks down "naturally" over 24 hours. But that only applies if carbidopa consumes all B6 1 to 1. It is bizarre that there is indeed no more info on this, but it is very unlikely that it is the case, because then almost all C/L users would be very severely B6 deficient and the medication would have no effect. Supplementing with an equal amount of B6 (P5P) therefore still seems unwise to me given the huge stacking that can take place. Only reporting B6 test results here with the B6 supplementation applied and the C/L doses can give some idea. Until then, unfortunately, no consensus... Of course, I would be very curious about your test result park_bear given the long period of time you have been taking P5P in high doses and your probably fixed pattern of C/L medication....
I will remove the AI calculation tomorrow to avoid further confusion.
Agreed that B6 dosage equal to carbidopa intake is way more than necessary. 50% is plenty. Are you comfortable with a recommendation like that?
It's an improvement, but sorry I’m not comfortable with that recommendation. I recently applied the 50% myself, but this again caused a much too high vitamin B6 level after testing. At the moment I use 10% and a new test has to show whether this is enough for me (n=1). Research data on the interaction between B6 and carbidopa should still be available. I'm going to search further.
At the moment, you can only gain clarity by having your B6 level tested. In the latest studies, this is also always emphasised as in the conclusion of “Refractory Seizures Secondary to Vitamin B6 Deficiency in Parkinson Disease: The Role of Carbidopa-Levodopa”, June 2022
“Despite growing evidence supporting carbidopa-levodopa-associated vitamin B6 deficiency and its critical import, clinical documentation is sparse, suggesting under-recognition. We recommend screening of vitamin B6 levels, especially in patients requiring high and increasing doses of carbidopa-levodopa and in those with poor nutrition.”
karger.com/crn/article/14/2...
Edited my post to say:
healthunlocked.com/cure-par...
"Personally I take 70 mg of B6 as P5P and I take C/L 25/100 2 1/2 times daily for a total of 62 mg of carbidopa daily. So I have enough B6 in circulation that it will never all be disabled by the carbidopa. But such amounts have been too much for some people. To arrive at dosage the safest course is to test and adjust supplementation accordingly. See comments: healthunlocked.com/cure-par....
This report from the EFSA Panel on Nutrition that did not distinguish between pyridoxine and P5P suggests an upper limit of 12.5 mg: efsa.onlinelibrary.wiley.co.. "
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