Vitamin B6 participates as a coenzyme in over 100 different biochemical reactions. When it does so it is converted to the inactive form, pyridoxine. The body contains a recycling loop that restores the pyridoxine to the active form, P5P. Vitamin B2 is required for this process. People with Parkinson's are commonly deficient in B2. A deficiency will result in excess pyridoxine, which is toxic. Toxicity results from pyridoxine occupying sites that require the active form of B6, which causes symptoms similar to B6 deficiency. This includes peripheral neuropathy. Vitamin B6 supplementation got a bad reputation as a result of using pyridoxine. The active form, P5P, does not suffer from this problem. People taking levodopa medication need to supplement because it depletes B6. Running out of B6 has dire consequences. For more detail see:
"PLP [the medical term for P5P] concentrations of more than 5.1 µg/L have been traditional indicators of adequate vitamin B6 status in adults... Pyridoxal 5'Phosphate (PLP), the most clinically significant coenzyme form of vitamin B6, is the form most commonly measured in plasma"
"86030973 VITAMIN B6, PLASMA 30552-4 Pyridoxal phosphate [Another term for PLP/P5P]"
These tests are useful in case of B6 deficiency, but not toxicity. Pyridoxine is not measured by a test which only measures the active vitamer, P5P. If your P5P level is in range but your pyridoxine level is high, it will be toxic but the test will register OK. On the contrary, if your P5P level is high but your pyridoxine level is low, you are likely in good shape even though the test says otherwise.
In other words, in the case of B6 toxicity the existing test is worse than useless because it does not measure what is actually toxic and may instead give a misleading result.
Vitamin B2, riboflavin, is non-toxic and there's no danger in supplementing plenty of it. Anyone suffering B6 toxicity should immediately commence B2 supplementation. In general this is a good idea for Parkinson's patients.
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park_bear
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I think the above is only a part of the whole picture. ALL B vitamins seem to work together, but measuring, quantifying, assessing, and supplementing them is particularly difficult. Despite ongoing research, there are still too many missing pieces of this complex puzzle to fully understand their interactions and make optimal supplementation recommendations, such as the influence of the carbidopa intake. Given the pivotal role of B6, it seems nevertheless wise to measure your B6 PLP levels. If there is a deficiency, you know that you should take extra P5P. Even better, if you also get a B2 test, it could provide a possible explanation for why your PLP levels are low.
In my personal opinion, if you have a deficiency, like most PWP, it's best to take a B-complex with bioactive B vitamins, including B6 (P5P) and B2 (riboflavin), with normal low values. The goal is to achieve or maintain balance. I don't believe that high-dose monotherapies contribute to that. If your B6 PLP levels are normal or high, I wouldn't recommend taking extra B6 (P5P.). With low doses of 1 to 2 times the recommended daily amount, the risk of potential pyridoxine accumulation is limited.
Thank you for your explanation. No matter how challenging the subject is with our somewhat different perspectives, I believe we both see the importance of checking this individually for PD and the need for further research. A good resolution for the new year.
If vitamin B2 is deficient, B6 P5P may test low yet pyridoxine may be high. In this case B6toxicity will continue until the B2 deficiency is remedied. According to this study: scielo.br/j/bjmbr/a/BM4WLJB...
"Abnormal [low] riboflavin status in the absence of a dietary deficiency was detected in 31 consecutive outpatients with Parkinson’s disease (PD)... In contrast, only 3 of10 consecutive outpatients with dementia without previous stroke had abnormal riboflavin status" [emphasis added]
So if you're going to test, vitamin B2 testing is a mandatory accompaniment to testing vitamin B6 P5P.
If you already have B2 in a B complex, the chance of a B2 deficiency, just like for the other B vitamins, seems virtually excluded. So given the costs not a priority, but first wait and see the B6 result. There are also no alarming signals. My PD symptoms are pretty much back to the level of my diagnosis 3 years ago and my PN seems to be recovering slightly... 🙏
I have no disagreement with whatever is working for you personally.
However, as a matter of general advice to others, I do not believe it is safe to say that the small amount of B2 supplementation In a B complex or multivitamin is sufficient to remedy the deficiency. Exactly how much is needed by Parkinson's patients taking medication is unknown and needs to be studied. However, the good news is Vitamin B2 is non-toxic and may be supplemented in quantity safely
Glad you're getting a bit of improvement in the peripheral neuropathy.
Beware of taking a huge excess of vitamin B6 in the presence of carbidopa/levodopa, a cautionary tale: I started taking a supplement that had relatively large amounts of complex B vitamins (specifically the one labeled number two below) had 100% (400 mcg) folate, 1667% (100 mcg) vitamin B12 and 5000% (100 mg) of vitamin B6 (based on daily requirement from our diet). Over a period of several days I started feeling stiffer, weaker as if my medicine had stopped treating my Parkinson’s. I especially noticed it one day while playing golf because I had lost significant yardage on my shots, I was breathing heavily, and I was totally out of sync with my golf swing. Just in general, my entire body was not functioning well. Timing wise, I was taking the complex B vitamin pill with my early morning carbidopa/levodopa pill on an empty stomach. Something was suddenly (not subtly) wrong with the way I was feeling, and the only new addition to my treatment strategy was this complex B vitamin pill. There had to be an explanation.
As stated, levodopa medication depletes vitamin B6. The reason for this is that if carbidopa encounters B6, the two will bind together irreversibly, inactivating both....So if taken together orally, levodopa medication and B6 will inactivate each other. If possible, P5P should be taken 2 hours apart from levodopa medication. If that is not possible, separate P5P from levodopa with a meal." [emphasis added]
Thank you for your posting. I respect your opinion and try to follow your advice when possible. As per your recommendation, I recently added P5P to my supplements list. The timing coincided with a change in my Levodopa from 25/100 ER to 50/200. ER
I always have to be careful with my sensitive stomach For example, i got nauseous taking Levodopa IR but I tolerated the small dosage of the ER version.
Since. I added the P5P and switched the Levodopa my stomach has been upset. I googled PSP and it can cause nausea Yesterday, i stopped taking the P5P in order establish more clearly the nausea causation I have not conclusively determined anything yet but i would appreciate your opinion I am also curious if other people have been bothered by nausea after taking Levodopa and how long before the stomach adjusts, if ever? Thanks in advance.
I tried searching and was unable to find a reference of that kind. I'm not aware of any reports of P5P causing nausea. Be that as it may, you are taking the right approach - undo the changes one at a time to see which one caused the nausea.
Can someone help me understand the relationship, if there is one, between NAD+ and the rest of the B - Vitamins. My understanding is that B3 is converted into NAD. If one is taking NAD+ does that have an impact on B6 or B2...
Sorry it seems I missed this earlier. As far as I know B3/NAD has no direct impact on B6 or B2. These are all so important to bodily functions that a deficiency in any one will have broad effects.
I have started taking P-5-P B6 50mg since today morning. The serum B6 test results are expected next Friday. I am not taking any other B vitamins at present.
My question is what to look out for regarding overdose? How long does B6 stay in the body? Does it accumulate? Any other precautions to take?
As far as I know B2 is non-toxic. I take 100 mg daily. Not sure what the minimum should be. Reference: scielo.br/j/bjmbr/a/BM4WLJB...
Vitamin B6 supplementation prevents depletion due to levodopa medication, and the ill effects that would arise should that occur. If a person was suffering from depletion it would improve the resulting Parkinson's exacerbation, but otherwise does not have a direct effect upon Parkinson's symptoms as far as I know.
In the above linked study patients who were suffering from vitamin B2 deficiency, which was everyone tested, showed a benefit from B2 supplementation (They also quit red meat, not clear what effect that had)
Thank you PB. I have seen the study and I was unable to understand the logic behind dose selection of 30mg every 8 hrs (150mg per 24 hrs) and banning red meat...
If you are striving for a doubling of your required B2 value, which seems more than enough to me, you should look at what the daily need is multiplied by the absorption factor needed to realise that. That kind of data is hard to find, while it's important to know how to supplement. However, in my post about the B complexes, I mentioned the existence of a key to some B vitamins, including B2. The calculation factor for the natural form and the synthetic form do not differ that much in that research. B2 has a fairly low Bioavailability. Rounded off, you should take about 20 x the daily required amount, i.e. 20 x 1.4 mg = 28 mg
“My question is what to look out for regarding overdose? How long does B6 stay in the body? Does it accumulate? Any other precautions to take?”
>>>
As mentioned earlier, taking an extra 50 mg of B6 is too much, in any form. A well-dosed bioactive vitamin B complex provides enough B6, along with the important B2.
Due to the extremely long half-life of B6, which is about a month, taking a daily dose of 50 mg can lead to excessive accumulation. Additionally, B6 has a high bioavailability. Just 3.5 mg, which is approximately 2.5 times the daily required amount of 1.4 mg, can already double your desired B6 level. This is likely more than enough to compensate for any potential 'carbidopa damage'.
Based on the test results from other members of the HU community, it is evident that an intake of more than 5 mg per day already leads to an overdose, even for PWP who are taking high doses of Carbidopa.
“Any recommendations for a good quality B-Complex?”
>" A well-dosed bioactive vitamin B complex provides enough B6,"
As far as I can recall I've not seen evidence from you that this is known to be true for a person taking large amounts of levodopa medication
>" taking a daily dose of 50 mg can lead to excessive accumulation"
I've taken 70 mg daily for years and never had a problem.
>"This is likely more than enough to compensate for any potential 'carbidopa damage'."
I see no actual evidence at your link, just a long list of supplements.
>"Based on the test results from other members of the HU community, it is evident that an intake of more than 5 mg per day already leads to an overdose"
Have you impartially tabulated the evidence including from those who tolerate higher doses B6 well?
Have you ever investigated the role of vitamin B2 deficiency in B6 toxicity?
Did you ever check your B2 levels when you were suffering from B6 toxicity?
Here we go again PB 😉 Thanks for your critical reply.
“ A well-dosed bioactive vitamin B complex provides enough B6,"
As far as I can recall I've not seen evidence from you that this is known to be true for a person taking large amounts of levodopa medication
>>> As I have mentioned to you before, the collected test results do not seem to indicate a very significant impact of carbidopa. A slight supplementation appears to be sufficient, but it is in any case essential!
“taking a daily dose of 50 mg can lead to excessive accumulation"
I've taken 70 mg daily for years and never had a problem.
>>> That doesn't mean you don't have a massive overdose. That's why I'm still very curious about your test results! You cannot recommend 70 mg of B6, even as P5P, due to the risk of peripheral neuropathy. "If it doesn't help, it doesn't harm" is never wise, but with B6, it's dangerous! Unfortunately, I speak as you know from experience...
“This is likely more than enough to compensate for any potential 'carbidopa damage'."
I see no actual evidence at your link, just a long list of supplements.
>>> It was the first link to the reply in which the small but relevant study is mentioned:
“Based on the test results from other members of the HU community, it is evident that an intake of more than 5 mg per day already leads to an overdose"
Have you impartially tabulated the evidence including from those who tolerate higher doses B6 well?
>>> Yes, indeed. There were certainly PWPs who had not yet developed a PN, but of course those with neuropathic problems responded in particular.
“Have you ever investigated the role of vitamin B2 deficiency in B6 toxicity?”
>>> I have read the studies you have provided with great interest and I absolutely see the importance of B2 supplementation in combination with B6 (and the other B vitamins). That is one of the reasons why I advocate for the use of a moderately dosed B complex for all PWP’s.
Did you ever check your B2 levels when you were suffering from B6 toxicity?
>>> Unfortunately, I did not test my own B2 levels at the time because I was not yet familiar with this phenomenon. But later, with B2 supplementation through my B complex, it was less relevant and also too precious. The many B6 tests already cost me a fortune, but have saved me from a catastrophe.
>"the collected test results do not seem to indicate a very significant impact of carbidopa. A slight supplementation appears to be sufficient, but it is in any case essential!"
Let us compare your mention about what test results seem to indicate against this detailed report: sciencedirect.com/science/a...
"Abnormal B6 levels have been reported in 60 of 145 PwPD (41.4% relative frequency). Low B6 levels were reported in 52 PwPD and high B6 levels were reported in 8 PwPD. There were 14 PwPD, polyneuropathy and low B6. There were 4 PwPD, polyneuropathy and high B6. There were 4 PwPD, epilepsy and low B6. Vitamin B6 level was low in 44.6% of PwPD receiving levodopa-carbidopa intestinal gel and in 30.1% of PwPD receiving oral levodopa-carbidopa."
Sorry - your mention is outweighed by this actual data.
>" That doesn't mean you don't have a massive overdose."
You are apparently defining "overdose" as being above an arbitrarily set level of the active, non-toxic vitamer of B6, that fails to take into any account the level of the toxic vitamer.
>"the first link to the reply in which the small but relevant study is mentioned..."
All that study says is that levels of B6 in healthy subjects increased in response to increased intake. Hardly a surprise.
I'm glad you find vitamin B2 of interest, but that is not enough. Even people taking very low amounts of vitamin B6 in accordance with your recommendation have reported B6 toxicity. Vitamin B2 deficiency is the likely culprit. As documented in a study I linked to higher up, B2 deficiency is commonplace amongst Parkinson's patients, and 90 mg daily is well tolerated. I know you are willing to allow some vitamin B2 supplementation, but why not opt for abundance?
I find nothing in what you have reported to indicate that someone taking 200 mg or more of carbidopa daily will be adequately supplemented with only 2 mg or so of B6, and failure to adequately supplement has been documented to result in disastrous consequences. You may be leading people astray. I reserve the right to call it out as I deem fit.
I submit that abundant vitamin B2 supplementation resolves the issue of B6 toxicity. You seem to have plenty of time and energy to devote to the issue of B6 toxicity. I suggest more of it should go to study of abundant B2 as the solution.
🐻Your injection of a bit of humor into this debate appreciated🐂
🐻The report you are referring to is actually a confirmation of my own experience and the reason why I spend so much of my precious time on this discussion. Identifying the problem is extremely important, but while I, along with apparently millions of other PWPers, struggle with this, there is no guidance provided on how to approach B6 supplementation. I still don't know of any research that provides the scientific basis for it. Unbelievable!!!
In a rather amateurish way, I have therefore started my own database with B6 test results to have some sort of reference point. As a long-term high-dose P5P user, your potential test results could also be very informative...
From this database, you can see that even PWP with high doses of carbidopa have an overdose of B6 with a relatively low amount of B6 intake. There is even a test result well within the B6 reference range with an intake of 250 mg carbidopa and 0 mg B6 supplementation!!! I do see a relationship, but the impact of carbidopa is not as significant as assumed.
Therefore, there must be other causes for the frequently observed B6 deficiency in PWP. I personally suspect that the frequently discussed chronic stress plays a role in this. It often leads to a deficiency in B vitamins, particularly B6, B5, B12, but also the here much discussed B1, B2, B3 en B9. The mention of B5, pantothenic acid, is remarkable. Research shows a disruption of pantothenic acid levels across PD.
Because all B vitamins are important for your energy metabolism, along with vitamin D, C, magnesium, and zinc levels, supplementing with a reasonably dosed multivitamin may be preferable to a B complex.
While I acknowledge the importance of B2, I want to dedicate my precious time also to other insights. There is so much more to explore 😉
As not being a native English speaker, I unfortunately lack finesse in injecting humor into this debate, but I'm doing my best. At least I'll try to do justice to the metaphor used, 🐂
>"As a long-term high-dose P5P user, your potential test results could also be very informative..."
No. It's safe to say the result would be very high, from which you would again allege I am overdosed. Yet I have no B6 toxicity. The level of non toxic P5P is irrelevant as regards toxicity. The toxic vitamer of B6 is what needs to be measured. As I've already explained, this is pyridoxine and that is not measured. It seems I'm not being heard here. If I choose to not respond further it would be for this reason.
>"Therefore, there must be other causes for the frequently observed B6 deficiency in PWP. I personally suspect that the frequently discussed chronic stress plays a role in this."
If this were the case B6 deficiency would be widespread but that is not so. B6 deficiency among people with Parkinson's taking levodopa medication, particularly high doses, is a fact. Finding exceptions does not invalidate this evidence. B2 status is the essential variable that likely explains the difference, because B2 is needed to recycle the toxic form of B6 into the useful, non-toxic P5P B6. It is not possible to properly study B6 deficiency or toxicity without paying attention to vitamin B2 levels.
Your English is excellent - I would never have guessed that you were not a native speaker.
"Levodopa is typically administered with a peripheral decarboxylase inhibitor (PDI), benserazide or carbidopa. PDIs bind irreversibly to pyridoxal-5-phospate (PLP), the active form of vitamin B6."
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park_bear made a very compelling argument for taking P5P (active B6)
URIDINE: Why LD/CD Users Should Consider It
trying to consolidate b6 facts
