What are your experiences with the consequences of a (tested) too low vitamin b6 level.

[Esperanto]

In connection with the worsening of my peripheral neuropathy that has occurred in addition to my PD, it appears after a blood test that my B6 level is extremely low (only 12% of the minimum needed value). This probably explains the onset of the PN and the poor efficacy of the Sinemet's L/C medication.

However, I cannot imagine that I am the only PwP who has a problem with vitamin B6 breakdown and the resulting damage due to the carbidopa. Beside the neuropathy, these are for me mainly insomnia, fatigue, sharp decrease in Creatine/muscle strength, weight loss and reduction in cognitive ability.

To verify if I am on the right path with the B6 boost ( in the form of P5P), but also as an argument to cancel the skepticism from the doctors, I ask you to share your experiences with me.

1) Are these extreme low values more common in PD? Logically, because of the fairly common L/C medication, they should be.

2) What are the symptoms that have occurred with you?

3) How do you combine the supposed degradation of B6 by the carbidopa versus the extra B6 supletion.

Thanks again for your responses!

🍀

[Hidden]

healthunlocked.com/cure-par...

healthunlocked.com/cure-par...

[Esperanto in reply to Hidden]

Thanks for this link from 10 months ago. Regarding your low b6 level at the time, how low was it and has it since improved? Did / do you have any symptoms that arose from the b6 deficiency?

[park_bear]

Regarding doctor skepticism:

B6 is a vitamin, which by definition means the body cannot make it on its own. B6 is required for countless essential biological processes: en.wikipedia.org/wiki/Vitam...

" PLP [B6] is involved in many aspects of macronutrient metabolism, neurotransmitter synthesis, histamine synthesis, hemoglobin synthesis and function, and gene expression. PLP generally serves as a coenzyme (cofactor) for many reactions including decarboxylation, transamination, racemization, elimination, replacement, and beta-group interconversion"

Since your B6 level is only 12 percent of the minimum needed for health, that may well be responsible for all the problems you have set forth above. This clearly needs to be remedied, and then see what problems still remain.

Do not expect validation from medical doctors on this issue. They are propagandized to believe that medication can do no harm and that supplements can do no good. Unfortunately too many of them buy into into this.

[Esperanto]

True, but I just don't understand the straightforward thinking among doctors. PD brings me little good, but one of the beautiful experiences is realizing how impressive the interconnectedness of your life processes are.

Nevertheless, I find it remarkable, given few responses, that apparently there is not so much collateral damage from B6 deficiency anyway as a result of the L/C medication so readily prescribed.

[Lyricist]

the only comment I can add is that when I told my neurologist that I was taking B vitamins, he told me to avoid B6 on the grounds that it interfered with absorption of L-dopa.

[Esperanto in reply to Lyricist]

This interaction with levodopa is precisely the problem. The carbidopa breaks down the B6. The levodopa needs the B6 to form dopamine and the carbidopa to provide the workshop for the dopamine production.

I understand that there is often a certain reluctance among doctors about experimenting with dietary supplements. In this case however, there really is a very serious B6 deficiency, which is responded to quite laconically: DIY...

If I am on the right track with this self-diagnosis, then I really need help from a professional who is versed in this matter to find a balance between medication and supplements in terms of correct dosage, form and time. I will keep searching, but for now my only hold is HU to stop the neuropathie and also stabilise my parkinson’s. But should you suspect something else could be going on here I'd love to hear it!

[park_bear in reply to Lyricist]

B6 interferes the absorption of levodopa because most prescription levodopa meds include carbidopa, which is important for absorption. If B6 if it meets up with carbidopa in the digestive tract, they form a complex disabling both, which causes levodopa to be poorly absorbed. It is also the case that carbidopa greatly increases the body's utilization of B6. As stated above B6 is essential for a vast array of biochemical processes. A person should be supplementing B6 in an amount similar to the daily consumption of carbidopa. One should separate taking B6 from taking carbidopa/levodopa by an interval of 2 hours, or if this is not possible, by a meal. In light of the foregoing, and from Esperanto's experience, it is contrary to health to recommend simply avoiding B6.

Additional writing by me on this subject: healthunlocked.com/cure-par...

The cause of B6 toxicity: healthunlocked.com/cure-par...

[Esperanto in reply to park_bear]

Meanwhile, I am not sure if the vitamin B6 supplementation should equal the amount of carbidopa. After more than 2 months !!! I just finally got my vitamin B6 value from the lab. Not easy to take your supplement accurately this way. The result is 185 nmol/l. The normal level here has to be between 20 and 121 nmol/l. So the dosage is probably too high. I had taken the weight of carbidopa as the norm as suggested at HU. I will now halve the dose. For you already get your basic intake through a regular healthy diet. After all, overdosing also has risks for the peripheral neuropathy that I developed partly due to the previous severe B6 deficiency. My impression is that it has worsened further over the past month.

[park_bear in reply to Esperanto]

>" overdosing also has risks for the peripheral neuropathy"

NOT with the active form of B6, P5P. Please read healthunlocked.com/cure-par...

[Esperanto in reply to park_bear]

Indeed, but there is stil (the danger of) the vitamin B6 paradox: researchgate.net/publicatio...

I do vitamin B6 supplementation with the "safe" P5P for that reason. But I am not convinced that P5P is harmless in all cases. Hinz's unreliable studies did rightly draw attention at the time to B6 deficiencies being caused by the action of carbidopa, but not about the possible interaction the other way in my opinion. The pharmacists do mention the minor impact of B6 on C/L medication at a maximum daily B6 supplementation of 10 - 25 mg. But little is known about the impact of the recommended higher doses of B6 on carbidopa. However, my own experience n=1 shows that after a spectacular 70% reduction in my C/L in a few weeks, the effectiveness of the medication slowly declines. Possibly due to the now too high B6 level and/or due to the much lower half-life of B6 compared to carbidopa which may cause possible stacking. Moreover, due to the reduced intake of carbidopa, there is less degradation of B6. The one to one B6 supplementation with the amount of carbidopa seems too much in the langer therm. Hard to find a balance in this. All studies say you should determine the supplementation in consultation with your neurologist....  😃Perhaps you have a better idea?

[park_bear in reply to Esperanto]

There is not a danger of the B6 paradox - toxicity -with P5P. The reference you cited is the same reference that I cited in my above link. It says: “In conclusion, the present study indicates that the neuropathy observed after taking a relatively high dose of vitamin B6 supplements is due to pyridoxine. The inactive form pyridoxine competitively inhibits the active pyridoxal-5′-phosphate. [P5P]”

As to the potential of excess B6 in circulation inactivating too much carbidopa, the symptom one would expect from that event would be nausea.

“effectiveness of the medication slowly declines”: That would be due to Parkinson's progression rather than B6 in circulation.

[Esperanto in reply to park_bear]

While P5P will not be toxic per se, it is likely to have its effect on the process of dopamine formation. However, if the carbidopa is deactivated prematurely, then the B6 / P5P would do what is warned about when B6 levels are too high, which is the premature activation of levodopa, resulting in too little dopamine being produced in the brain. This is what I am currently experiencing, without nausea. I know there is constant PD progression, but at this stage, like the B6 deficiency six months ago, there must be an underlying complication. I am not resting until I have clarity on that. Besides, a 3-month honeymoon is really too short…. 😉

[park_bear in reply to Esperanto]

I've only experienced this sort of thing when taking B6 and carbidopa at the same time. I have been taking B6 in excess of my daily carbidopa usage, at separate times, for years now and have not experienced any problem.

You said your B6 level “is extremely low”. Have you increased your intake since making that statement? Are you separating B6 from carbidopa ingestion by at least 2 hours? If so, it is a simple matter to test your idea by reducing your B6 consumption.

[park_bear in reply to Esperanto]

In light of your recent post regarding taking c/l 10/100, if your carbidopa levels are marginal, it would make sense that abundant B6 would make a difference. I would suggest trying c/l 25/100 rather than reducing B6

[Esperanto in reply to park_bear]

Thanks for your advice, also as an expert by experience. I have indeed been carefully following the "park_bear protocol". Initially with immense success, but now the balance seems somewhat upset. In any case, I am reassured that any excess P5P does not cause problems with you. Getting back to the original question of the post, after the extra dosing according to the PB protocol, have you had your B6 levels tested ? Am very curious about the outcome!

I will take your advice to heart and offset the B6 doses with the amount of carbidopa used. Increasing the amount of carbidopa is proving difficult in Europe with Sinemet 25/100 IR. This has not been available for some time. However, the CR version is. Although you can't actually split the CR I am thinking of taking 4x half a 25/100 CR and half a 10/100 IR, a total of 70mg of carbidopa. Is that an option?

[park_bear in reply to Esperanto]

My C/L ER tablets, the generic equivalent to CR, are scored to enable splitting. Not necessarily true of all tablets. The worst that could happen would be a CR dose becomes IR. So, yes, you can try this.

[Bfp69]

Esperanto, I totally sympathize with your frustration in not finding medical guidance for this important issue! Sorry I don’t have anything concrete to add. I’m a caregiver for a man who has had PD for at least 17 yrs, the first 13 of those on c/l and now just mucuna. When I learned here recently about the importance of proper B6 levels, I checked the Raw B Complex he takes and it has 10 mg. So I called his dr to see if we could get him a blood level test and they said no- that it was excreted in the urine and nothing to worry about- even when I said I learned that too much or too little can cause PN and other problems. I’m bewildered that the medical industry doesn’t understand this about the body!! What on Earth?!

[park_bear in reply to Bfp69]

Doctors are propagandized to believe that vitamins don't matter and all too many of them buy into it. Until someone shows up with having convulsions due to no B6:

Refractory Seizures Secondary to Vitamin B6 Deficiency in Parkinson Disease: The Role of Carbidopa-Levodopa

karger.com/Article/FullText...

[Esperanto]

Given the impact that vitamin B6 has on PD medications according to both older and recent studies, as well as the manufacturers of L/C themselves, I am surprised that there are so few reactions. Perhaps carbidopa does not automatically break down the B6 in everyone due to a matter of predisposition. Of course, it is also possible that many PWP do not notice the deficiency because B6 is hardly ever tested for. In that case, unnecessarily high doses of L/C will often be prescribed, with all the ensuing complications.

In my case, the DIY "emergency medication" with vitamin B6 (P5P) seems to have immediate effect. The neuropathy does not seem to be getting worse and is causing fewer symptoms. In addition, after one week I was able to halve my Sinemet medication without any problem and a further reduction seems even possible!!! The negative spiral may have been broken, and perhaps even a belated “honey moon” on the horizon for me 🍀

I'll keep you posted if the improvement continues!

[park_bear]

Turns out that B6 deficiency in patients taking Carbidopa levodopa is commonplace. See: journals.lww.com/clinicalne...

“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. Patients with low vitamin B6 had been treated with larger doses of L-DOPA/CD, although the differences did not have statistical significance.”

[Esperanto in reply to park_bear]

Unfortunately, the recommended supplementation with B6 with the daily amount of carbidopa does not appear to be wise for everyone. For me, it leads to an exces of vitamin B6 resulting in a further severe deterioration in peripheral neuropathy, despite the P5P form. On the advice of the neurologist, I stopped taking the B6 acutely, after the same exces can still be seen even after a half of the dose. The website of the Dutch nature dieticians confirmed this phenomenon with different patients.

Perhaps this has to do with the long half-life of B6 of 55 hours. Frank Church shows the accumulation that this can result in.

Https://journeywithparkinsons.com/2017/09/11/  b-vitamins-folate-b6-b12-reduce-homocysteine-levels-produced-by-carbidopalevodopa- therapy /e

Exactly how B6 causes problems is not yet entirely clear. Complaints can apparently arise at low and high doses, but also completely absent at those same doses. Supplementation with vitamin B6 in the active form of Pyridoxal-5-phosphate (P5P) has the advantage that the vitamin no longer has to be converted by the body into its biologically active form, a process that does not turn out to be equally efficient for everyone. In addition, due to the better efficacy, a lower dose is sufficient. For most people, the P5P is also harmless in higher doses, but processing vitamin B6 appears to depend on the genes. Researchers from the Institute of Molecular Medicine, School of Medicine, Trinity College Dublin and the Centre for Human Genetics investigated at the time. Several gene variants B6 (SNPs) occurred in the blood of 2345 healthy people. These gene variations affected vitamin B6 status in the blood.

pubmed.ncbi.nlm.nih.gov/259...

Further research should be conducted into what these findings mean for vitamin B6 functions and susceptibility to neuropathy.

[park_bear in reply to Esperanto]

I regard this as a serious matter. I certainly do not wish to be giving out bad advice.

How much P5P were you taking that caused the peripheral neuropathy?

Which brand was it?

Have you quit completely or are you taking lesser amount now?

Thanks for details.

[Esperanto in reply to park_bear]

Thank you for your involvement! When diagnosed with PD, exactly 2 years ago, there may already be the first signs of a kind of neuropathy PN. Slight tingling and ‘dormant’ feet but not yet chronic. Unfortunately, no B6 values were measured at the time. After diagnosis, the PN probably deteriorated at a rapid pace due to the influence of the carbidopa on the B6. After the first detection of the severe B6 deficiency, only half a year ago, in addition to the miraculous improvement in PD symptoms, P5P supplementation (> Vit4ever) also resulted in a stabilization of the PN. I adjusted the amount of P5P exactly with the reduction in the carbidopa, now 65 mg per day. However, about 2 months ago the PN deteriorated again, which was also observed with an EMG. There turned out to be even radiance to the hands now. Then I more than halved the dose of B6 to 25 mg. After the result of last week's blood test, with almost identical far too high B6 values, I completely stopped supplementation. By the way, the neurologist for neuropathy informed me that they never prescribe B6 for more than 2 months. It was also remarkable that my B1 value was suddenly much too high. Although specialist neuropathy doctors report a risk for neuropathy in excess thiamine, but I have not found any studies demonstrating Thiamine toxicity for conventional doses. Only in some cases toxic effects have been described for daily doses in the gram range (Marshall et al. 2014). I will measure the B values again in 2 months, but it is difficult to consume the PD and PN soup.

[park_bear in reply to Esperanto]

Vit4ever appears to be a good vendor. They test all of their product for contamination with heavy metals and bacteria.

Nonetheless I cannot shake the notion that you are suffering from pyridoxine toxicity. I wonder if Vit4ever would be willing to test their P5P product to verify it really is P5P and not pyridoxine.

[park_bear]

I'm wondering if you have experienced any improvement in the peripheral neuropathy as result of supplementing vitamin B12?

[Esperanto in reply to park_bear]

Thank you for your interest PB. After the worsening of peripheral neuropathy due to too high B6 (and other B vitamin values) I had applied a complete supplement stop, also for B12. With this I hoped to clarify which B vitamins are not sufficiently supplied with a normal diet. That turned out to be B6 again and the other B vitamins to a lesser extent. So 2 months ago I started modest supplementation again. The B6 with 25mg per day when using 65mg of carbidopa. The B12 also with a modest dose (I'm travelling so I don't have the jars with me). In a month I will have everything retested and depending on the result I will look at the new dosage. Simultaneously also a new EMG to check the development of the PN. If you had asked me 2 weeks ago, I would have said that makes it much worse. After 2 weeks of hiking in Spain, I turn out to be able to walk considerable distances again. Strange.

[park_bear in reply to Esperanto]

Very glad you are able to walk considerable distances again. Look forward to further updates when appropriate.

[Esperanto in reply to park_bear]

And here's the update PB. Today I got the result of a new B6 test: A serious overdose has been detected again. 🤔 As I wrote earlier, after my fasting period, I had adjusted my B6 dosage at 25 mg per day. In reality, that was an average of 20 mg per day because I forgot 1 in 5 times the dose or could not fit in because of the C/L medication. In the past period, the carbidopa intake was about 65 mg per day. So I took about 30% P5P compared to the carbidopa amount.

Just a quick look at the B6 results last year:

The desired B6 reference value: 5 to 15 µg/L

25 August 22 > 1.1 µg/L very severe deficiency, (no B6 supplement), 18 months after diagnosis, severe PD and PN symptoms, high C/L medication has no effect anymore.

24 January 23 > 31.3 µg/L significant overdose, (intake B6 = carbidopa), after initial huge improvement again worsening PD symptoms, but also PN

31 March 23 > 3.3 µg/L, again severe deficiency, (after 2 months of fasting of all supplements), PD situation improved again, PN fairly stable, but no improvement

20 July 23 > 26.8 µg/L, overdose again, (intake B6 = 30% carbideopa) PD situation similar to diagnosis and PN fairly stable, minimum C/L medication

So it has still not been possible to permanently get a 'normal' B6 value. My preliminary conclusion is that (for me) the impact of the interaction with the carbidopa is less than expected, but a more limited supplementation remains necessary.

[Jmellano in reply to Esperanto]

Interesting, i went back and look at at my B6 levels on earlier blood tests

blood test 1/25/22 B6 < 2.0

started B6 supplementation ( dont recall which supplement; if it was P5P or not)

blood test 7/5/22 B6= 35.3

stopped B6 supplementation

blood test 7/19/23 B6 = 3.0

[Esperanto in reply to Jmellano]

I didn't know I had a twin sister! 😀

[Jmellano in reply to Esperanto]

Lol

[park_bear in reply to Esperanto]

As I read this data it does not seem like the high levels of B6 made the PN worse. Also I would bet that the high limit in the reference range for B6 is based upon observations of pyridoxine toxicity rather than P5P. Likewise I wonder if your doctor is blaming B6 based upon pyridoxine toxicity as well.

[Esperanto in reply to park_bear]

It is difficult to objectively assess the development of the PN. In my first period of overdose, there was clearly deterioration. That was why I consulted a more specialised PN neurologist who eventually made the connection with the B6 vicissitudes, both the deficiency and the high overdose. He determined that the damage to the nerve pathways was so great that recovery was virtually impossible. Also no advice, as with the PD neurologist, how to arm yourself against further impairment. Only pain relief with side effects that you certainly don't need with PD. In 3 weeks I will have a new EMG investigation and hope to hear that the PN has at least not deteriorated.

I'm not sure about that, the tingling I now also feel in my hands. A certain habituation also occurs over time, the burning feet, the bizarre combination between numbness and pain. Any improvement can take years and seems to be quite painful. Are those the pain shoots I feel more often now? Always that hope..

[Butterflygrandma in reply to Esperanto]

Wouldn't a tablespoon of nutritional yeast be better than supplements that cause neuropathy ?

[Esperanto in reply to Butterflygrandma]

Nutritional yeast Is probably a valuable addition to our diet, high in vitamin B6 and a lot of other (B) vitamins, minerals and fibers. It turns out that either too little or too much of this vitamin B6 can cause peripheral neuropathy. Nerve damage that occurs from vitamin B6 as a neuropathy like stocking-glove phenomenon has also been signaled with yeast. A five gram teaspoonful of nutritional yeast provides 121-142 per cent of your daily requirement of vitamin B6. So overdose remains a risk, also with (a combination of) our diet, B6 supplements, B-complex multivitamins and in many additives to combi supplements. Due to the interaction with carbidopa there is for some of us an additional complication in PD to find a balance. So here too: have your B6 level tested regularly!

[Esperanto in reply to park_bear]

The EMG done yesterday. The hands and arms in particular showed significant improvement in the PN, probably because that is where the symptoms had started only six months ago. The earlier problems with my feet and legs, most of whose nerves would have been irreparably damaged, appear to have stabilised and in a few places even a barely measurable recovery was noted. 🎉 🎉Definitively, the B6 deficiency and overdose were identified as the cause and further investigations stopped. I ignore the neurologist's warning not to take B6 supplement for more than 2 months. To avoid a yo-yo effect I prefer a low P5P dose to find a balance combined with regular testing and continue with Art's (Chartist) advice except for the controversial Berberine : healthunlocked.com/cure-par... To this I recently added the supplement Propionate after Ethin's information : pubmed.ncbi.nlm.nih.gov/366...

The cost of the EMG was 100% reimbursed because it was supposedly PD related… Another small victory.

[park_bear in reply to Esperanto]

Glad there is improvement!