Levodopa Medications and Vitamin B6 - Cure Parkinson's

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Levodopa Medications and Vitamin B6

park_bear profile image
109 Replies

For the purposes of this post, levodopa medication refers to prescription medications like Sinemet, Rytary, or Madopar that contain carbidopa or benserazide. For simplicity when I refer to carbidopa that also includes benserazide.

Absent supplementation, carbidopa can deplete vitamin B6 and cause serious health issues:

Convulsions due to no B6 left: Refractory Seizures Secondary to Vitamin B6 Deficiency in Parkinson Disease: The Role of Carbidopa-Levodopa karger.com/Article/FullText...

"carbidopa, which is combined with levodopa to reduce peripheral levodopa conversion and minimize peripheral dopamine side effects, binds irreversibly with PLP [the active form of vitamin B6]. As a result, carbidopa-levodopa may cause vitamin B6 deficiency and associated sequelae, including seizures, especially in high doses... B6 is a cofactor in over 100 enzymatic reactions"

This irreversible binding will occur in the digestive tract if B6 and carbidopa are taken close together in time, inactivating both the medication and the B6. Allow at least two hours between taking one and the other. If this is not possible, separate them by a meal, or wait until you are fully into "on" time before taking B6. Once in circulation, some of the carbidopa will bind to and disable some B6, but this doesn't matter as long as you have sufficient carbidopa and B6.

Dosage and Avoiding toxicity:

The pyridoxine form of vitamin B6 is toxic and should not be ingested in large quantities. It is commonly found in multivitamins. The nontoxic form of vitamin B6 is pyridoxal-5-phosphate (P5P) and is readily available as a supplement. Further details regarding this issue can be found here: healthunlocked.com/parkinso...

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. Occasionally such amounts have been too much for some people. Here are the relative risks of B6 deficiency versus overdose: 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." [emphasis added]

The safest course is to test and adjust supplementation accordingly. For additional commentary see: healthunlocked.com/cure-par... and also this report from the EFSA Panel on Nutrition that did not distinguish between pyridoxine and P5P, which suggests an upper limit of 12.5 mg: efsa.onlinelibrary.wiley.co... See also: healthunlocked.com/cure-par.... healthunlocked.com/cure-par...

B6 deficiency is commonplace in patients taking levodopa medication:

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."

This can shorten lifespan:

Association of Serum Vitamin B6 with All-Cause and Cause-Specific Mortality in a Prospective Study researchgate.net/publicatio... "Compared with sufficient vitamin B6, deficient (HR = 1.37... ) vitamin B6 level were significantly associated with a higher risk for all-cause mortality."

B6 deficiency can also cause peripheral neuropathy. Vitamin B12 deficiency is also commonplace and can also cause neurologic problems.

Updated post on this subject here: healthunlocked.com/cure-par...

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109 Replies

hmmmmm....

Hikoi profile image
Hikoi

Interesting and clearly explained thanks.

jeeves19 profile image
jeeves19

Nice. I’m taking uridine after a post by WackaMole about a year ago. Park Bear, what about other vitamin depletion’s ?

park_bear profile image
park_bear in reply to jeeves19

Not that I am aware of at this time. Yes, I just saw that uridine post and read up on it. Do you think it has been helpful?

jeeves19 profile image
jeeves19 in reply to park_bear

Too early to say. If I never get dyskinesia then we might be on to somerthing! Google it?

parkinsondoc profile image
parkinsondoc

Park_Bear you are wrong and looking at only the small picture. Carbidopa and benserazide both bind irreversibly (not neutralize) vitamin B6 and the B6 enzymes. Your statement of, "as long as you have enough B6" in the system is not correct. If you give enough B6 to compensate for the carbidopa, you induce a naked L-dopa state where all the problems of L-dopa that the carbidopa was intended to be used for are once again present. In the naked L-dopa state you need six times more L-dopa to get the same effects as you do with carbidopa. This means giving six times more carbidopa and six times more vitamin B6. You are that point are officially chasing your tail. The bottom line, if you are using carbidopa and getting benefits from it you are in a state of depleting your vitamin B6 and B6 enzymes with all the problems that go with this drug induced nutritional deficiency. You must remember that the enzyme which catalysis metabolism of L-dopa to dopamine is a B6-enzyme. As you deplete this enzyme it can appear that Parkinson is getting worse.

park_bear profile image
park_bear in reply to parkinsondoc

You are guilty of selectively quoting one word out of context. What I actually wrote was: "bind together and neutralize each other." The meaning of this is clear. You say:" bind irreversibly (not neutralize) " - A distinction without a difference. Lest anybody else be similarly confused, I added the word "irreversibly" to my text , and changed "neutralize" to "disable".

" If you give enough B6 to compensate for the carbidopa, you induce a naked L-dopa state where all the problems of L-dopa that the carbidopa was intended to be used for are once again present."

Did you even read what I wrote? If so, you evidently failed to comprehend it or could not be bothered to try. The carbidopa is needed to do its work in the GI tract. If allowed to do so, and the B6 is ingested at a different time, the carbidopa is not interfered with. A plenitude of B6 then gets into general circulation where it is needed. If you are taking more B6 than carbidopa that guarantees you will always have unbound, active, vitamin B6 available in general circulation.

ElliotGreen profile image
ElliotGreen in reply to park_bear

Just for the record for future readers of this conversation, carbidopa activity is not limited to the gastrointestinal tract. It is also absorbed and does get into "general circulation", and this activity is significant. (However, it does not cross the blood brain barrier.) For example, see the citation:

ncbi.nlm.nih.gov/pubmed/109...

also:

"Carbidopa is distributed widely in body tissues except the CNS [central nervous system]."

glowm.com/resources/glowm/c...

I am not taking carbidopa/levodopa medication yet, but should I start, I would attempt park_bear's advice for offset dosing between C/L and B6.

However, I would be sure to have my B6 tested to make sure I wasn't too deficient.

I also don't think that park_bear fully counters this claim in the Hinz paper:

"Carbidopa and the active metabolite of benserazide, trihydroxybenzylhydrazine, irreversibly bind to and permanently deactivate PLP and PLP-dependent enzymes.18,19,70–74"

So there isn't a "safe refuge" for vitamin B6 or its dependent enzymes. Temporally offset B6 supplementation may help counteract the effects of carbidopa on this wide array of enzymes, but it's going to be a balancing act.

What I’m not entirely clear on is whether carbidopa just “steals” a B6 from the enzyme, or if it permanently shuts down the whole PLP-enzyme assemblage. I’m guessing that Hinz may have overstated it somewhat in stating that PLP -dependent enzymes are “permanently deactivated”. It may just be that the PLP is stolen and permanently deactivated, but another molecule of B6/PLP could get the enzyme rolling again. But I don't know. [I have actually sent an email to some Italian researchers who may be able to shed light on this question.]

However, the picture is somewhat worse (or uncertain) than park_bear was suggesting.

park_bear profile image
park_bear in reply to ElliotGreen

I am not disputing the cited claim in the Hinz paper. I am merely pointing out that if one takes more B-6 (PLP) than can be consumed by the carbidopa there will always be B-6 available from which to make the needed enzymes.

ElliotGreen profile image
ElliotGreen in reply to park_bear

One of the things I'm trying to figure out (and the reason I've tried to contact some researchers) is this:

Is it just the B6 (PLP is the active form) that is permanently deactivated? Does an enzyme just have its PLP stolen? Or is the whole enzyme permanently deactivated and shut down? If it's the latter case, there's a whole lot more work needed to remake the enzyme the just some extra B6. If the body has to re-synthesize all of these proteins and enzymes every time you dose with carbidopa, that's a lot of work.

park_bear profile image
park_bear in reply to ElliotGreen

I commend your thoroughness.

The first question that comes to my mind is whether Hinz's claim that carbidopa disables B6 dependent enzymes in general is correct. References 18, 19, 73, 74 appear to be irrelevant. I took a more careful look at references 70-72:

Bertoldi M. Mammalian Dopa decarboxylase: structure, catalytic activity and inhibition. Arch Biochem Biophys. 2014;546:1–7.71.

sciencedirect.com/science/a...

Wu F, Christen P, Gehring H. A novel approach to inhibit intracellular vitamin B6-dependent enzymes: proof of principle with human and plasmodium ornithine decarboxylase and human histidine decarboxylase. FASEB J. 2011;25(7):2109–2122.72.

fasebj.org/doi/abs/10.1096/...

Cellini B, Montioli R, Oppici E, Voltattorni CB. Biochemical and computational approaches to improve the clinical treatment of dopa decarboxylase-related diseases: an overview. Open Biochem J. 2012;6:131–138.

ncbi.nlm.nih.gov/pmc/articl...

As far as I can tell none of these support his contention that B6 dependent enzymes are in general inactivated by carbidopa. Unless I am missing something, Hinz and company are making claims that are not supported by the references given for them. So at this point I do not see any evidence to support Hinz's claim.

ElliotGreen profile image
ElliotGreen in reply to park_bear

ingentaconnect.com/content/...

I haven't looked at it beyond the abstract, but this 2016 review states:

"carbiDOPA and trihydroxybenzylhydrazine, the active metabolite of benserazide, are substrate analogues both endowed with a hydrazine function, which irreversibly bind not only to DDC but also to free pyridoxal 5’-phosphate and pyridoxal 5’-phosphate-dependent enzymes. Therefore, the lack of DOPA decarboxylase specificity, responsible for various side effects and adverse reactions, is a negative factor in such treatment of the disease."

That doesn't look good to me.

ElliotGreen profile image
ElliotGreen in reply to ElliotGreen

I contacted one of the authors of that study. Sci hub doesn't have it, so it'll be a little bit more of a challenge to find the full article.

ElliotGreen profile image
ElliotGreen in reply to ElliotGreen

See also Hinz ref 7:

journals.plos.org/plosone/a...

Overlapping authors with the review I just linked.

"they irreversibly bind to free PLP and PLP-enzymes"

park_bear profile image
park_bear in reply to ElliotGreen

This is an unreferenced text which may merely be repeating Hinz's assertions. I did a Google scholar search on carbidopa+ "pyridoxal 5’-phosphate-dependent enzymes" and did not come up with any evidence. I only found a bit of background:

ncbi.nlm.nih.gov/pmc/articl...

ElliotGreen profile image
ElliotGreen in reply to park_bear

Maybe. But given that at least one of the authors has done work on carbidopa's interactions with these enzymes before, and it's a review article, I doubt they would blindly make that assertion in the abstract without further backing. But I don't know. I sent another email to the author, asking for a PDF copy of the article.

I'm sure it has references. That journal just doesn't have its references listed on the website. They are grayed out for all of the articles.

park_bear profile image
park_bear in reply to ElliotGreen

Very well. I will await evidence supporting this claim.

Be all this as it may, let us not lose sight of the main point, upon which I believe we agree: carbidopa levodopa medication results in the need for additional vitamin B6.

Despe profile image
Despe in reply to park_bear

I (husband) follow your relevant expertise, PB. 50mg P5P in the B complex you actually helped me find. Is it enough? His total carbidopa is also 50mg. Do you think he should increase B6?

Thank you.

park_bear profile image
park_bear in reply to Despe

This issue has not been studied in clinical trials so it is hard to be sure. To be on the safe side you could increase - I take 100 mg. Or you could have his B6 levels checked next time you have blood work done.

Edit - upon rereading, an equal amount, 50mg, ought to be enough.

Despe profile image
Despe in reply to park_bear

Thanks, PB. Guess I can find another B complex with a little higher P5P. He hasn't had his B6 level checked that I can think of.

Despe profile image
Despe in reply to park_bear

He did have a Nutr-Eval test prescribed by Cleveland Clinic FM . The results indicated that he is (before starting MP + carbidopa) in high need of ALL B-vitamins, including B6. FM doc prescribed 50mg B6, daily.

glenandgerry profile image
glenandgerry in reply to Despe

Which B complex is that Despe?

Despe profile image
Despe in reply to glenandgerry

Sorry for my delayed response. :( I get it on Amazon and you have to search the specific liquid complex otherwise you won't find it. They hide the good products.

B Complex by Sigform. I believe it's the only B-complex with all the right forms of B vitamins.

in reply to Despe

Despe, are you still able to get it on Amazon? I can’t find it. I’m looking for the liquid form. Are you familiar with Mary Ruth’s liquid B?

Despe profile image
Despe in reply to

CC,

I guess they try to hide the good supplements. :) You have to search it by its name: Liquid B-complex, Sigform.

Vitamin B-Complex 8oz, Liquid Formula

Brand: SIGFORM

5.0 out of 5 stars 4 ratings

in reply to Despe

Thank you Despe, Well, I found a B 12 by Sigform but not the complex. I’m going to compare the ingredients with Mary Ruth’s.

I just ate a very green banana and thought of my friend Despe! You are the one who informed me about the health benefits of them. 😊

Despe profile image
Despe in reply to

CC, I found B-complex, Sigform, last night on Amazon. Strange. If you have an amazon account, sign in and then look for it.

Mary Ruth's B complex is missing B-1 plus the amount of the Bs is not enough. I do take her multi vitamin as well as the night time liquid, and her liquid probiotics. They are tops!

in reply to Despe

Thank you Despe! ❤️ I will look again. I confess that much of what I do in here is while in work calls so I’m juggling! I was considering the multi from Mary Ruth’s and I use the probiotic. Thank you!

Despe profile image
Despe in reply to

You are welcome! :)

Despe profile image
Despe in reply to glenandgerry

Since you are in UK, here is another good one which PB found and recommended:

metabolics.com/b-complex-li...

glenandgerry profile image
glenandgerry in reply to Despe

Wow Despe, thank you so much for this, it's saved me a lot of legwork!

Despe profile image
Despe in reply to glenandgerry

Always, glad to help. :)

bassofspades profile image
bassofspades

ncbi.nlm.nih.gov/pmc/articl...

park_bear profile image
park_bear in reply to bassofspades

My post is a response to that article.

Jezq profile image
Jezq in reply to bassofspades

ooh - article retracted, March 2021

bassofspades profile image
bassofspades in reply to Jezq

Dr Hinz got a lot of BS for going against big pharma so they scrubbed a lot of his work.

Esperanto profile image
Esperanto in reply to bassofspades

It is so easy to always blame “big pharma” for everything. Of course, it is important to keep an eye on those companies, but Hinz was trying to enrich himself through manipulating of his research.

Stephen Barrett M.D. recently listed the latest state of affairs in this recent report

A Skeptical Look at Dr. Marty Hinz and His Views of “Neurotransmitter-Related Diseases” September 10, 2023

quackwatch.org/11ind/a-skep...

silvestrov profile image
silvestrov

The problem I have with Hinz's hypothesis as to carbidopa causing death in PD is its laziness. They authors rely on the timeline of levodopa as therapy versus levodopa plus carbidopa and compare their respective death rates. It is too simple and does not explain the following:

Aspiration pnuemonia is the number one cause of death in PD and how does carbidopa cause aspiration pnuemonia (AP)? AP is also the leading cause of death for Progressive supranuclear palsy, Huntington's disease and is common in Multi system atrophy.

What do all these diseases have in common? Brain stem degeneration. So how does carbidopa cause brain stem degeneration? And it should be noted L-dopa is not a therapy for Huntington's disease. They actually use haloperidol which causes drug-induced parkinsonism.

As an aside low dose haloperidol may be a future therapy for PD:

researchgate.net/publicatio...

Are there any studies supporting a deficiency of pyridoxine leads to pneumonia? Yes, one study from 1949... (not a rock solid argument)..

The effect of diet on the susceptibility of the mouse to pneumonia virus of mice; influence of pyridoxine administered in the period before as well as after the inoculation of virus.

ncbi.nlm.nih.gov/pubmed/181...

If carbidopa/benserizide are the cause of death in PD then all PD patients should develop peripherol neuropathy prior to death and PN develops in 1/5 PwP. In addition (form the Death Rate article):

"Systemic vitamin B6 concentrations inversely correlate with mortality induced by coronary artery disease, colorectal cancer, stroke, heart failure, and atherosclerosis."

Stroke:

"This study shows a significantly increased risk of ischemic stroke in PD patients. Further studies are required to investigate the underlying mechanism."

journals.plos.org/plosone/a...

An older study:

"The carotid duplex scanning results could not provide a potential explanation for the relatively low occurrence of stroke in Parkinsonian patients, because most strokes are related to carotid atherosclerotic lesions while the TCD results might reflect a diminished blood supply secondary to a decline in tissue metabolism."

sciencedirect.com/science/a...

Missing link in Parkinson's disease found: Discovery also has implications for heart failure

Heart disease:

"Researchers at Washington University School of Medicine in St. Louis have described a missing link in understanding how damage to the body's cellular power plants leads to Parkinson's disease and, perhaps surprisingly, to some forms of heart failure."

The author's note that mitochondrial dysfunction is the connecting point between developing PD and heart failure in PwP.

sciencedaily.com/releases/2...

Colorectal cancer?

Conclusion:

"Parkinson’s disease is inversely associated with CRC risk."

sciencedirect.com/science/a...

There is not doubt that Sinemet/Benserizide are imperfect drugs and much maintenance is required to have them work properly. In B12 and folate must be taken to prevent the rise of homocysteine and methylmelonic acid levels (which are associated with peripheral neuropathy). Other methy donors like betaine hydrochloride and choline should be considered too. L-dopa methylates parkinsonsnewstoday.com/201... And EGCG from green tea should be considered as adjuvant L-dopa therapy because it can 'modestly' inhibit levodopa methylation: europepmc.org/articles/PMC2...

Etc, etc....

Here is the proverbial 'kicker'. PwP have lower rates of certain cancers, like colorectal cancer, with the exception of melanoma/non-melanoma skin and breast cancer(s). Surprisingly, there is some evidence that carbidopa has anti cancer activity:

Carbidopa Reduced Tumor Growth in Lab Studies of Cancer

parkinsonsnewstoday.com/201...

"The most widely reported reduced risks in PD patients are cancers of the prostate, lung, bladder, stomach, colorectal, blood, and uterus (Table 1). While the lower risks of lung, bladder, and colorectal cancer, all smoking-related cancers, in PD patients are generally undisputed, stomach, leukemia, and uterine cancers fail to achieve significance in some studies for a clear inverse association."

"Evidence also links PD to an increased prevalence of a few cancers (Table 1), in particular non-melanoma skin cancer."

translationalneurodegenerat...

If anyone reading this is interested in lowering their non-melanoma skin cancer risk, take 2 x 500 mg of niacinamide/nicotinamide per day:

"Oral nicotinamide was safe and effective in reducing the rates of new nonmelanoma skin cancers and actinic keratoses in high-risk patients."

nejm.org/doi/full/10.1056/N...

But this reduction of cancer rates in the west seem to be different with those from people of Chinese descent (a Taiwan study):

"The researchers found Parkinson's was not related to an elevated risk of developing thyroid, ovarian or breast cancer. However, the people with Parkinson's were found at an increased the risk for 16 other forms of cancer, including lung, urinary tract and brain cancer, as well as leukemia and melanoma."

ibtimes.com/parkinsons-dise...

Could carbidopa use be a contributing factor in the inverse relationship between PD and cancer in western society and not using carbidopa in Taiwan the cause of the increased rate of cancer? (Assuming they don't use carbidopa/levodopa.)

Everyone who has read my posts know I am pro vitamins, minerals, amino acids, fatty acids, herbs as either primary or adjuvant therapies for PD, but, after reading the Hinz article I was dissatisfied with their hypothesis.

I have communicated with people on the Hinz protocol and like any other therapy for PD, it can help improve PD symptoms but its results are variable. Some people cannot take the high dose of levodopa due to cramping and nausea. It helps some people more than others but it is a viable therapeutic alternative.

Oh well here is my two bits.

park_bear profile image
park_bear in reply to silvestrov

ncbi.nlm.nih.gov/pubmed/?te...

"Carbidopa inhibited pancreatic cancer cell proliferation both in vitro and in vivo"

worth noting. They used human pancreatic cancer cells in an animal model.

parkinsonsnewstoday.com/201...

" We believe that the reduced incidence of most cancers in Parkinson’s disease patients is due to carbidopa.”

silvestrov profile image
silvestrov in reply to park_bear

Sinemet/madopar are not the best drugs (I hope they are soon replaced) but this could be one of their benefits. I read the Hinz death rate hypothesis and thought it is a weak argument. Like I wrote, show me how the major cause of death for PwP, aspiration pneumonia, is caused by a pyridoxine deficiency and I am all ears.

reedboat2 profile image
reedboat2 in reply to silvestrov

Rich - thanks for the well reasoned reply. Any idea how Mucuna compares with Carbidopa/ Levadopa with regards to B6 absorption? Thanks- John G

silvestrov profile image
silvestrov in reply to reedboat2

I posted a thread which featured an article showing the equivalent dose of sinemet to mucuna pruriens and mucuna pruriens to madopar:

healthunlocked.com/parkinso......

As for taking P5P/pyridoxyl 5 phosphate/B6 with mucuna P. they obviously cannot be taken simultaneously but P5P is used with the proverbial 'Hinz protocol':

"...the following cofactors were administered daily: 1) vitamin C 1,000 mg; 2) calcium citrate 220 mg; 3) vitamin B6 75 mg; 4) folate 400 mcg; 5) l-lysine 500 mg; 6) l-cysteine 4,500 mg; 7) selenium 400 mcg."

ncbi.nlm.nih.gov/pmc/articl...

Comment: 400 mcg of selenium is the maximum safe upper limit daily amount. I take 200 mg/day of selenomethionine.

Large doses of standard pyridoxine can cause peripheral neuropathy so I do not use pyridoxine hydrochloride: ncbi.nlm.nih.gov/pubmed/363...

And P5P does not cause PN:

"The use of supplemental P5P has not been associated with toxicity, although the inactive form, pyridoxine, has been associated with reports of peripheral neuropathy.

Also. "The antituberculosis drug isoniazid can result in a functional vitamin B6 deficiency.

Anti-parkinsonian drugs benserazide and carbidopa cause vitamin B6 depletion by forming hydrazones."

spectracell.com/media/uploa...

Since P5P will decrease the effectiveness of mucuna pruriens levodopa if taken simultaneously, I would take it at bedtime (provided you do not take L-dopa at bedtime) because:

"B6 nutritional status has a significant and selective modulatory impact on central production of both serotonin and GABA – neurotransmitters that control depression, pain perception, and anxiety. P5P is a cofactor in the synthesis of these neurotransmitters."

Same link as above. Since serotonin and GABA can help induce sleep (and relieve stress), taking P5P at bedtime may help with your sleep. Many natural sleep aids have P5P as a component:

amazon.com/Designs-Health-I...

The dose of P5P supplements are at 20, 50 or 100 mg. Considering Hinz et al, use 75 mg, 50 mg/day should be fine.

amazon.com/s/ref=nb_sb_ss_i...

park_bear profile image
park_bear in reply to silvestrov

re "Large doses of standard pyridoxine can cause peripheral neuropathy" -can happen, rarely, with moderate doses:

"Case report A 49-year-woman, who had taken 75 mg B6 daily together with multivitamins*, zinc and magnesium for 2 years, and whose serum B6 level was > 34 ng/ml, complained of paraesthesia of hands at night, ‘biting ants up her legs, electric shock pains in her head’, numbness of her finger tips and itching between the shoulder blades. Examination revealed patchy areas of hypersensitivity to stroking with cotton wool on her back and lower limbs, especially her shins. Reflexes and muscle power were normal, and L‘hermitte’s test negative. On stopping B6 in July 1985 all symptoms eased within 3 months. She restarted 50 mg B6 in August 1986 and by November 1986 had a return of the same neurological symptoms, the same areas of hypersensitivity and her serum B6 was again > 34 ng/ml. She has again been advised to stop B6."

*multivitamin may have additional B6

silvestrov profile image
silvestrov in reply to park_bear

I had a long week and am finally able to respond.

Like most things under the sun, B6 in Parkinson's therapy is not new. Previously I posted the doctoral presentation, "Beans, roots and leaves, A History of the Chemical Therapy of Parkinsonism", opus.bibliothek.uni-wuerzbu...

The author noted:

"In the 1950's, however, a number of European workers, particularily in Germany and Austria, recommended a high dose therapy in which the daily dose was set in the region of 600-1,400mg; up to 750mg/day was administered intravenously, while higher doses were required if taken orally. The major benefit was seen in the relief from rigidity and the reduction of tremor, accompanied by a general increase in physical strength and improvement in mood; Sigwald's group also found an effect on akinesia. Marked improvements in specific tasks, such as the co-ordination of movement and speech, were also noted with some surprise. The therapy was most effective for patients in the early stages of the disease and after a long period of treatment with the vitamin, as summarized by Finke (Neurological Clinic Neuemuhle, Kassel-Niederzwehren):"

"The vitamin B6 therapy must be seen as the preparation of choice for thetreatment of parkinsonism (especially of early identified cases). Significant objective improvement in cases which are 4 or 5 years old, however, cannot be expected even with high doses of becauue of the severity of damage to the globus pallidus and substantia nigra."

"Finke believed that the progression of the disorder could be slowed by pyridoxine therapy, so that is was not merely another symptomatic treatment. Some authors (for instance, Hartmann-von Monakow, who had employed the vitamin in the treatment of parkinsonism since 1945) found that pyridoxine could even be used alone in early cases; it was, however, worthwhile at any stage of the disease, as it could be combined with any other anti-parkinsonian medication, produced no side effects, improved the temper of the patient and increased his general physical fitness and resistance to infection."

Side effects were not noted in this high dose usage of pyridoxine for PD, though they are not recommended because, as you (along with the following article) have noted:

Revisiting the evidence for neuropathy caused by pyridoxine deficiency and excess.

"Pyridoxine deficiency and excess have been implicated as a cause for peripheral neuropathy. As a result, unrelated neuropathies are often treated with pyridoxine based on questionable evidence. However, neurological practitioners frequently discourage patients from taking pyridoxine in excess of 50 mg/d given concerns around the development of a toxic sensory neuronopathy. There is no systematic review to support either of the 2 practices. To address this gap in knowledge, we reviewed the available literature on neuropathy attributed to pyridoxine deficiency and excess. Based on the current limited data, it can be concluded that very low doses of daily pyridoxine are required to prevent peripheral neuropathy. There is inadequate evidence to support routine pyridoxine supplementation in patients with disorders of peripheral nervous system. Supplementation with pyridoxine at doses greater than 50 mg/d for extended duration may be harmful and should be discouraged."

ncbi.nlm.nih.gov/pubmed/251...

As previously noted P5P, pyridoxyl 5 phosphate will not cause PN at 50 mg doses but it has to be used cautiously when used with levodopa, M. pruriens or synthetic, without a decarboxylase inhibitor, carbidopa/benserizide. P5P will speed the conversion of levodopa into dopamine in the body and decrease its effectiveness.

Dec 37, 1971

Pyridoxine Antagonism of Levodopa in Parkinsonism

"Since the decarboxylation of dopa to form dopamine is dependent upon pyridoxal phosphate, Duvoison and co-workers1 hypothesized that pyridoxine might enhance the therapeutic effects of levodopa. Accordingly, they administered pyridoxine hydrochloride to patients with parkinsonism who were receiving maintenance doses of levodopa. They found that large doses of pyridoxine completely eliminated the clinical effects of levodopa, while smaller doses reduced or abolished its therapeutic activity or only dyskinetic side effects. This was associated with a reduced rise in plasma dopa levels following levodopa administration. Other workers have also reported reduced clinical activity of levodopa following pyridoxine.2-3 The purpose of the present study was to correlate the effects of pyridoxine on the therapeutic activity of levodopa with its effects on absorption and metabolism."

jamanetwork.com/journals/ja...

Hinz et al, used P5P at 65 mg/day because of prior use of carbidopa by the patient. "Since the decarboxylation of dopa to form dopamine is dependent upon pyridoxal phosphate..." and carbidopa binds to P5P thus preventing decarboxylation in the body; but P5P also passes the blood brain barrier and is required in the brain for decarboxylation of levodopa into dopamine. Hence the high dose use of P5P by Hinz to replete P5P in the brain (caused by carbidopa-induced deficiency).

park_bear profile image
park_bear in reply to silvestrov

Indeed, P5P avoids toxicity. More here: healthunlocked.com/parkinso...

ElliotGreen profile image
ElliotGreen in reply to silvestrov

I don't have time at this moment for a full response to this at this moment. But I want to address the first couple of points.

1) I think the ecological method that Hinz undertakes is valid and not "lazy". Yes, further investigation is possible. But we have a broad mechanism (depression of B6 levels and the resultant repression of many necessary enzymes that are dependent on B6). We also have a connection between carbidopa medication and a switchover from decreasing to increasing death rates.

2) As to your next two paragraphs: Carbidopa need not increase the rate of aspiration pneumonia to increase the death rate of people who take it! Carbidopa does not need to increase the rate of brainstem degeneration to increase the death rate of people who take it! I'm not sure where you were going with these arguments.

The notion that carbidopa, by depressing B6, can depress many enzymes does not lead to a hypothesis that it would increase death by one particular mechanism. It leads to a hypothesis that there would be a general decrease in health and well-being, and that that could be associated with an increased death rate. In this sense, taking a broad look at overall death rate seems valid to me.

park_bear profile image
park_bear in reply to ElliotGreen

Agree. Specifically: carbidopa, by depressing B6, can depress many enzymes and lead to a general decrease in health and an associated increased death rate. It could also lead to a vicious cycle of progression - needing more carbidopa levodopa, further depressing B6.

Kia17 profile image
Kia17

Park_bear

High amount of vitamin B6 can contribute to Neuropathy which in many cases irreversible.

I think that’s too much B6.

park_bear profile image
park_bear in reply to Kia17

The cheap inactive pyridoxal / pyridoxine form is the one that can be toxic. This can be avoided by taking the active P5P form.

Kia17 profile image
Kia17 in reply to park_bear

“Vitamin B6 toxic effects – sensory & motor neuropathies, some not reversible”

google.co.uk/amp/s/painsand...

park_bear profile image
park_bear in reply to Kia17

The cited study can be found here: ncbi.nlm.nih.gov/pubmed/250...

"High dose pyridoxine is neurotoxic. Previous case reports were sparse and little is known about the clinical and electrodiagnostic findings. Three patients with pyridoxine-induced sensory ataxic neuropathy were studied and a review of the involved literature was performed. Three patients, aged 80, 83 and 83 years old, presented with sensory ataxia for 3-8 months. Examination showed signs of polyneuropathy and sensory ataxia. Six hundred milligrams of pyridoxine was consumed each day for 3-10 years, in the form of vitamin B1-6-12 combination tablet. Investigations for other causes of neuropathy were unremarkable."

600 mg is an overdose, and it is the pyridoxine form which should be avoided.

park_bear profile image
park_bear in reply to Kia17

I have now addressed pyridoxine toxicity in detail here: healthunlocked.com/parkinso...

MWLE profile image
MWLE

Sounds like another option is to take B6 as an injection to bypass the gut.

park_bear profile image
park_bear in reply to MWLE

Yes, that should work.

Despe profile image
Despe in reply to park_bear

Hello park_bear! Am looking for a good, liquid b complex with B6 in the form of P5P, 50mg. Can you/would you recommend a good one? I have been looking for one on line, but haven't found one. Thank you!

park_bear profile image
park_bear in reply to Despe

I did some searching and found the following. Have not used so not in a position to make a recommendation:

sigform.com/product/b-compl...

UK: metabolics.com/b-complex-li...

Canada: sunforceorganics.com/produc...

Despe profile image
Despe in reply to park_bear

Thanks, PB! I will order the US product.

Are you taking a B complex?

park_bear profile image
park_bear in reply to Despe

Seeking Health "B Minus", without folate and B12. Separately P5P and andenosyl-B12.

Despe profile image
Despe in reply to park_bear

Have you heard of Cobalt? Dr. Mischley recommended it for my husband along with Methyl B12.

park_bear profile image
park_bear in reply to Despe

I did a search and got mixed results regarding benefits vs. toxicity.

ncbi.nlm.nih.gov/pmc/articl...

sciencedirect.com/science/a...

Despe profile image
Despe in reply to park_bear

Oh boy. :( Thank you PB. She recommended it based on test results. He complains about weak knees, which prohibit him to walk fast, although at times he goes faster than me. We have to have another telemedicine appointment and go through the vitamins list we sent her. I will ask her more details then.

There are not many Cobalt minerals on line, but I found this one from Amazon. MOTHER EARTH Minerals, Cobalt, 200 +/- per million.

park_bear profile image
park_bear in reply to Despe

I have not studied this matter carefully and I do respect Laurie Mischley. If she can provide a journal reference that would be of interest.

Despe profile image
Despe in reply to park_bear

Gee, I don't know if I can ask that question, PB. Would it be appropriate to ask her for a journal of reference??

park_bear profile image
park_bear in reply to Despe

If requested respectfully as a means to further inform yourself I do not think it would be a problem, but if you are not comfortable asking for it no need to bother on my account.

Despe profile image
Despe in reply to park_bear

It's not going to be a life-long supplementation, just a couple of months.

Smittybear7 profile image
Smittybear7 in reply to Despe

Can anyone contact Laurie Mischley?. How can you become a patient of hers?

park_bear profile image
park_bear in reply to Smittybear7

seattleintegrativemedicine....

Despe profile image
Despe in reply to Smittybear7

PB below answered your question, as well as I PMd you.

LAJ12345 profile image
LAJ12345 in reply to Despe

There is cobalt in cobalamin ie vitamin b12. I wonder if you can get it from that? This says

“Medically valid uses

As part of B-12, cobalt prevents pernicious anemia. It’s also needed to keep the nervous system working well.

Unsubstantiated claims

There are no claims based upon cobalt as a single element.

Recommended intake

As part of supplements, cobalt is measured in micrograms (mcg). The average adult intake of cobalt is 5–8 mcg per day. A safe Recommended Dietary Allowance (RDA) for cobalt hasn’t been set yet.

Trace amounts of cobalt are found in most foods. Foods high in vitamin B-12 are the only source of cobalt used by the body.

It’s best to take cobalt in vitamin B-12.

If you have a cobalt deficiency, this also means you have a vitamin B-12 deficiency. Anemia is a main cause of a cobalt deficiency. This is the case with pernicious anemia. Symptoms can include numbness, fatigue and tingling in your hand and feet. Over time, the condition also leads to decreased nerve function.”

urmc.rochester.edu/encyclop...

Despe profile image
Despe in reply to LAJ12345

LAJ, Dr. Mischley recommended that my husband takes cobalt for a short term course (approx. 2 months) based on tests. No anemia though.

Despe profile image
Despe in reply to park_bear

amazon.com/Designs-Health-T...

Checked with Dr. Mischley and said yes my husband can take this Tricobalamin, 3 forms of B12. I have ordered it.

park_bear profile image
park_bear in reply to Despe

Nothing wrong with cobalt as B12!

Smittybear7 profile image
Smittybear7 in reply to Despe

How do you get in touch with DrMischley?

Despe profile image
Despe in reply to Smittybear7

seattleintegrativemedicine....

Her website.

ElliotGreen profile image
ElliotGreen in reply to MWLE

I don't think injecting B6 is the answer. Carbidopa is not only active in the gastrointestinal tract. It is distributed through the rest of the body except the central nervous system.

park_bear profile image
park_bear in reply to ElliotGreen

Carbidopa and B6 are much diluted when they enter into general circulation as compared to the GI tract. While there is still potential for these molecules to encounter each other and form an inactivated complex, that occurs to a much lesser degree than if taken together as oral doses. That is my experience at any rate - abundant B6 in circulation does not seem to interfere with my carbidopa levodopa, whereas if I take them together the carbidopa levodopa is ineffective.

sharoncrayn profile image
sharoncrayn

Dr. Heinz doesn't say this or write this. Re-read his studies. If you can't figure it out, get back to me.

Sharon

Resano profile image
Resano

Hello. Concerning the timing, what would you suggest if one takes the E/R version of Levodopa ? Thanks.

park_bear profile image
park_bear in reply to Resano

Suggested timing of at least two hours separation applies to the ER version. Personally I take the ER version exclusively.

Resano profile image
Resano in reply to park_bear

Hello. If I remember well, Dr Costantini pointed out that B6 is a facilitator of the decarboxylase whereas Carbidopa or Benserazide (in the case of Madopar) are powerful inhibitors. From there, he warned against too much of circulating B6. What’s your opinion ? Thanks in advance.

park_bear profile image
park_bear in reply to Resano

Vitamin B6 is essential for for a vast array of vital functions:

sciencedirect.com/topics/ch...

"Vitamin B6 plays a role in the metabolism of protein, carbohydrates and fats, the production of neurotransmitters and the formation of nicotinic acid. It is vital for maintaining a healthy nervous system, skin, muscles and blood. One of the central roles of this vitamin is in protein metabolism where it helps regulate the balance of amino acids in the body. It is also closely involved in hormone production."

Accordingly, in my opinion it is essential to have it circulating in abundance. The only restriction is to not let it meet up in the G.I. tract with carbidopa.

Resano profile image
Resano in reply to park_bear

There is no question about the multiple benefits of B6. The actual concern is (I am quoting from your paper): “once the B6 is clear of your GI tract the carbidopa will meet up with the enzyme that converts levodopa to dopamine, and disable it, which is what is supposed to do.”

In these conditions, outside the GI, will not too great amounts of B6 continuously and consistently ENable the above enzyme (B6 being a facilitator, not an inhibitor), thus letting levodopa to be converted into dopamine outside the brain?

-and causing, by the same token, potent side effects such as tremors, stiffness and so on?

I’m sorry, Park_bear if my question sounds too naive. Thanks for your patience.

park_bear profile image
park_bear in reply to Resano

It is a good question and not naïve at all.

Reference: Dopa-decarboxylase Inhibitors

sciencedirect.com/topics/ne...

"AAAD is found in the cells lining the GI tract, the liver, pancreas, kidney, heart, and peripheral nerves. It is also found in the endothelial cells of blood vessels and in neurons and astrocytes within the CNS. Since AAAD is present in the GI wall, liver, and endothelial cells, the oral administration of levodopa is subject to a significant first pass effect. The presence of AAAD in endothelial cells that compose the BBB is particularly important, given levodopa's need to enter the brain for its anti-Parkinson's effect... Tritiated distribution studies reveal that 40–70% of carbidopa and 66–74% of benserazide are absorbed from the gut."

Therefore the action of carbidopa upon the lining of the GI tract is important, but also important is its action at the endothelial cells that compose the BBB.

So why is it that vitamin B6 and carbidopa meeting up in the GI tract is to be avoided but this is less of an issue for vitamin B6 in circulation? The answer is if these two are taken by mouth at the same time they meet up together in a restricted space at high concentration, and so most will form a complex together and thereby inactivate each other. If the vitamin B6 is taken separately at a different time, some of it is absorbed by the tissues and what is left over is distributed in 5 liters of blood. So when carbidopa is subsequently taken, that portion which makes it into circulation is exposed to only a dilute concentration of vitamin B6, and therefore a much lesser portion is inactivated, and enough gets to the endothelial cells of the BBB to be effective.

I do take a high dose of B6 at a different time than my carbidopa levodopa and the carbidopa still seems to be effective.

pdkid profile image
pdkid in reply to park_bear

Thank you so much for the wealth of B6 knowledge! I keep going back to reference it. Wondering what your "high dose" of B6 is. ⭐

park_bear profile image
park_bear in reply to pdkid

70-120 milligrams. I try to take at least as much P5P as my daily intake of carbidopa.

Smittybear7 profile image
Smittybear7 in reply to park_bear

What is the difference between controlled release and extended release Carbidopa levodopa?

park_bear profile image
park_bear in reply to Smittybear7

Details here:

healthunlocked.com/cure-par...

Smittybear7 profile image
Smittybear7 in reply to park_bear

Thanks I just don't know which one would be better for me. Currently taking c/l every 8 hours. I started having some involuntary movements in December when the dosage was increased to 11/2 pills am,1 afternoon and bedtime. I am also taking 5mg baclofen 2 times a day. I thought the increased was causing the problem. So we cut back the 1/2 pill in the am. The involuntary movements seem to occur with in 2 to 3 hours after taking the c/l. Sometimes the involuntary movements come after exercise then subside. Not sure what to do. Tremors and shoulder shrugs are side effects of too much or too little medication?? When I first started on medication in October I don't recall any problems until the dosage went from 1/2pill 3times a day to 1pill3 times a day for a couple of weeks to 11/2 am 1 pm,1 bedtime. No noticable difference since cutting the 1/2 pill mid January. Any suggestions would be appreciated. Thanks so much for your time and help.

park_bear profile image
park_bear in reply to Smittybear7

Dyskinesias - involuntary movements including shoulder shrugs - are the result of too much levodopa being converted into dopamine at a given time. A timed release version - Sinemet CR or carbidopa levodopa ER, may help.

The immediate release version peaks and then subsides well before two hours has elapsed, however, there is an unknown delay between measured plasma levels and actual dopamine levels in the brain.

Smittybear7 profile image
Smittybear7 in reply to park_bear

Which one would be best to try and how soon will I see results?Thanks again for all your help. This is all so new to me. Could cr or er cause more of a problem? Would I need a dosage adjustment?

park_bear profile image
park_bear in reply to Smittybear7

They are equivalent. The generic carbidopa levodopa ER is probably cheaper and easier to get. You may need to increase the dosage as compared to the immediate release version.

The difference should be immediate - same-day or at most a day later.

Smittybear7 profile image
Smittybear7 in reply to park_bear

How much of an increase and if it is too much will I see symptoms worsen..

park_bear profile image
park_bear in reply to Smittybear7

You may need to increase the dosage by as much as 50 percent, but I would start out with the same dosage and just replace your midday dose for starters. Make changes slowly.

Smittybear7 profile image
Smittybear7 in reply to park_bear

I apologize for all the questions but it's very confusing to me.I should get the ER version. And eliminate the afternoon dose? Both of the neurologist and movement specialist suggested cutting the pills in half I'm taking them every 4 hours? Should I try that first?

park_bear profile image
park_bear in reply to Smittybear7

A half dose every four hours is another way to deal with the issue. Since your prescribers have suggested it you should probably try it. Personally I prefer to take the ER version every eight hours. If you decide switch to the ER version just use it to replace one dose initially.

Smittybear7 profile image
Smittybear7 in reply to park_bear

Does Er distribute the c/l better than ir?

park_bear profile image
park_bear in reply to Smittybear7

What do you mean by "distribute"?

Smittybear7 profile image
Smittybear7 in reply to park_bear

Is the dosage more evenly available er vs ir?

park_bear profile image
park_bear in reply to Smittybear7

Yes. That is the point of the chart the top of this page:

healthunlocked.com/cure-par...

Resano profile image
Resano

Thanks a lot for your time.

Hikoi profile image
Hikoi

I’m not so sure about Hinz. I know I wouldn’t trust what he says. After all he makes alot of money out of it. retractionwatch.com/2020/12...

park_bear profile image
park_bear in reply to Hikoi

No fan of Hinz either. My point in writing the post was that his protocol is not necessary to avoid problems with carbidopa and B6.

Smittybear7 profile image
Smittybear7

How much b6 should I take? currently taking c/l (25-100) every 6 hrs.Thanks

park_bear profile image
park_bear in reply to Smittybear7

That adds up to100mg of carbidopa. I would take a similar amount of B6 as P5P, not pyridoxine. Be sure to read this post to understand the difference:

healthunlocked.com/cure-par...

Smittybear7 profile image
Smittybear7

How do you determine how much B6 to take if you're takingc/l? Thanks

Esperanto profile image
Esperanto in reply to Smittybear7

That will be different for everyone. Depending on the C/L dosage, but also your absorbancy and diet. Most multivitamins and B- complexes often already contain (too) much B6, so extra B6 will probably in that case not be needed. Make sure you take the active form P5P as park_bear already indicated before and initially no more than 12 mg per day which is seen as a safe upper limit. Only with regular testing can you determine the right amount.

Smittybear7 profile image
Smittybear7

Thanks

gaga1958 profile image
gaga1958

Hi, this article was 6 years ago. are you still taking 70mg of P5P/100mg B2? do you feel your PD has progressed slowly or quickly? (I know that's subjective) Or is there anything you could say was of great influence over your rate of progression? How much do you exercise? Just curious about your journey.

park_bear profile image
park_bear in reply to gaga1958

I've continued taking 70 mg for most of this time, comprising two pills - 20 mg as part of a B complex and 50 mg of P5P only. Recently I have been omitting the 50 mg pill some of the time because I do not feel like taking an extra pill, and based upon others reports it may not be necessary.

The B2 is a recent addition and plan on continuing.

My Parkinson's symptoms have been pretty steady except for a recent exacerbation unrelated to B6/B2.

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