I see some real problems with all of this. Because I have a real life problem with treatment for B12, and due to crossover symptoms with PD did not know what was happening to me. In spite of intense treatment in the autumn for nearly 3 months, once injections are stopped within 3-4 days maximum I am back at square one physically, and within ten days every last dreg of benefit has totally disappeared, from that point on I continue downward trend.

This is not a nice condition, I am very ****ed off with it, and it does not get rid of my PD symptoms when I have an injection. In fact it does the opposite, the PD symptoms are clearly defined and I wear off. untreated with B12 I am so lacking in energy that I move hardly at all, which is quantitatively and qualitatively different from bradykinesia. What I can say is that my PD medication works better when I get B12. So I use a little less of it. The PD is relatively easy to manage, and the B12 is not, or not when I am not adequately treated.

Testing is a problem, once tested often the standards tests do not work.
There are several different forms of cobalamin, here are the ones I know, cyanocobalamin, methylcobalamin, hydrooxycobalamin, adenosylcobalamin. The last only rarely used, if I remember rightly. And in different countries they use different forms.

To get the bit where it needs to go, into your bones where marrow can be healed, and new platelets made properly; into your myelin so any plaques heal; into your brain, and into your mitochondria, is harder. The tiny amount you absorb of what you take may not ever get to the methylation point. For some of the reasons Muirann talks about, and a few more besides.

What is clear though is that there is a link between orally ingested ldopa and the methylation cycle, and there could be a link between folate and b!2.

I don't believe in the blanket rejection of synthetic drugs because they are toxic. So is deadly nightshade, even when it is totally organic and has never had chemicals on it. It is a huge market scam. Even choosing the non synthetic tablets and capsules indicated they have undergone some kind of processing.

But there could be something there. and it needs to be looked at properly and evaluated properly. Everything else is anecdotal. But first people need to be screened for all the various factors, and then started on B12/folate.

But again, even before that there needs to be an understanding that it could take time for a difference to be felt, and that damage could already have occurred that may not be easily reversible.

that's where I see the problem. I cannot see anyone doing a well monitored study for more than months. If it runs into years researchers will give up.

Lindy,
I am in the same boat as you regarding neuropathic pain accompanying pd and I cannot live in hope of some future solution as revealed in clinical trials. I can only work with the information to hand, as follows:

By doing 23andme and loading raw data to geneticgenie.org (all free) I'm aware of at least 15 methylation snps. The presence of the mthfr snp is an indicator that I need the more bioavailable methylfolate rather than folic acid to utilise b12. Also the bh4 pathway sometimes needs to be addressed first.

I recently listened to dr Ben lynch say in a podcast that people who are positive for the comt snp (me) do better on a mix of adenosylcobalamin and hydroxycobalamin rather than the methylcobalamin he usually recommends.

My functional medicine tests also revealed a severe deficiency in b1 thiamine. Such deficiency can cause severe neuropathy. Perhaps this is your problem too?

Dr Terry Whals talks about her experience recovering from MS has encouraged me to stay off drugs and eat healthy instead.

She lists some testimonials at her website: Click on the list of diseases on right to see some PD patients.

http://terrywahls.com/success-stories/
I've been trying to follow her diet the past 2 years and am slowly recovering from my PD. The addition of new information regarding DNA testing and the need to correct the mythlation cycle I believe will help even more. I'm still looking for a Doc who is MTHFR literate who can help.

Dr Whals is great. This a great link detailing her more recent data. I've been trying to follow her diet suggestions. Now am adding the MTHFR data to fine tune that. Tis a great time to have PD with all this new information to help us! Thanks.

Lindy-
Has the following been considered?

1- B-vitamins are notorius for their water solubility and quick washout. "A matter of days..."? Could something similar be going on with the B12? Due to my use of a bedside urinal at night for fall prevention, I am very attuned to my B-complex intake and the correlation for me at least is unmistakable. And the symptoms mimic PD everywhere I turn. Could you mimic B-12 in the same way with the new orals such as the methyl?

2- How about a possible UTI that makes itself known inversely to B status? When Bs are up the immune system is better able to control the UTI whch then flares as things reverse. The increase in inflammatory cytokines can play hell with PD symptoms.

Both these could be tested by a patient pretty easily. And it is quite a coincidence how the times and wearing off periods match.

Reverett, this is a wel known problem for people who are not actually absorbing B12, a bit like those of us with PD who don't get the full benefit of levodopa until we take another drug to help it get across the BBB.

I am pretty sure that I do actually have PD, and that the difficulty I have had with B12 is something to do with longterm use of levodopa/entacapone. However these are good drugs for me, and the biggest possibility is that B12 and levodopa are competing with each other and, as someone, maybe Muirann, said, levodopa is mugging my B12 stores. Without sinemet, and without entacapone I do not function well, all the usual. Without B12 I am impossibly tired, incapable of standing long, or walking more than a few yards at a time. I also have neuropathy of a kind that is common with B12 def not PD.

The point is that everyone excretes B12, this can be slightly slowed down by taking folate, which is also added as a daily dose because B12 in large doses requires folate at the methylation stage. You take them in tandem and watch your blood tests in case of having too much folate, which can give problems. B12 doesn't. It gets stored in minute amounts in the kidneys and in the liver. To replenish these stores orally you have to take 1-2 mg per day. For a infinitesimal amount to get to where it is useful. Parenteral administration on the other had gets to where it is needed, both to heal and to store something for the future.

Not to put too fine a point of it, and with a warning that this might be TMI, I am doubly incontinent when not being treated with parenteral B12. On the same day as the shot this resolves completely. If I do not get another shot by the 4th day this is starting to return. So I do not think the theory you advance works for me. What I do think is that improving the stores in the kidneys improves the bladder cycle, and the liver the digestive cycle. What the mechanism is I do not know. To heal damage done you need upwards of 6 months of frequent dosing if there is neuro damage, which I have. The other end of the scale is taking B12 for life, usually every other day. It is in all the literature, easy to find.

Crucially the methylation cycle is normalised and mitochondria everywhere become more functional. This increases energy and allows for normal living.
Patient find this approach works, the experts know it works, it is only the people in between who don't.

Muirianns post is good, I have a spit kit, and will use it when I can summon up enough saliva. Like many others it seems likely that I have a defect such as those she describes, though I am not ruling out bog standard Pernicious Anaemia, because my doctors have not got a clue what to do. Incidentally they have a woman of a similar age to me, who I have not met, who has longstanding MS, in exactly the same position. Like me she is being given injections every two months. Her life is in the same screwy place that mine is.

It is hard to know what to do. I believe there are lessons to be had from the B12/mitochondria/ neuro damage thing that may help with PwP. Especially as this is known to happen to long term l-dopa users, which I now am. Injections work for them if they can get past the barrier of ignorance that surrounds the whole issue.

There is a bunch of elderly people somewhere in this country who have had their treatment removed because of an almost magical and very unscientific view that 'they don't need it'. The person who told me about it said that previously they had all been diagnosed with dementia and were going downhill, until treated with B12/folate. When I asked whether they had neuro conditions I was told nearly all, had they were long time survivors of about 5 conditions that any of us would recognise, including PD. At that point in time they were retreating into dementia, and the person concerned could not do a damn thing about it. It reminded me a bit of Awakenings. It shouldn't be like that though. This is a cheap drug, easily available, and well-documented. Patients are having to jump through hoops to get it.

I think that eventually for some of us the methylation cycle will be found to be important, but at this stage is the jury is still out, and not in a hurry at all.

More evidence of the correlation between methylation and PD

CONCLUSION: Our findings provide support for the synergistic effects of polymorphisms in the folate metabolic pathway genes in PD susceptibility; the increased PD risk would be more significant in carriers with the polymorphisms of MTHFR, MTR, and MTRR genes.

http://europepmc.org/abstract/MED/21...kXuB5Ep6T1g.10

For some reason that link wouldn't load, so I cut and pasted the text you gave and got this:

http://europepmc.org/abstract/MED/21...kXuB5Ep6T1g.10

htthttp://europepmc.org/abstract/MED/21070756p://

just curious how you treat your pd symptoms. you'd tried the hinz protocol, was that to control symptoms?
so far you've tried the cutler chelation protocol after removing 11 amalgams and still take 600mg of alpha lipoic acid daily, you tried the hinz protocol - was that to control symptoms?, , are attempting to follow the terri wahl protocol. just curious, when you were diagnosed, what your symptoms are and what you take for your pd. anything helping or are you taking what you take hoping it may help? most newbies at least say if/when they were diagnosed. your 1st post was asking about dr. paneri.

The link should take you to a study done at the Dalin Tzu Chi Hospital in Taiwan, which I happen to know is an excellent hospital, as is the organisation, Tzu Chi, that runs it. Only time will tell if these methylation things will be relevant to PD. I am finding that my PD symptoms are quite distinct from B12etc., though superficially they may seem similar. An example of this is biilateral neuropathy but unilateral right sided rigidity, which has not changed much since 1995. those with B12 and no PD symptoms have few of the hall mark signs we do, no FOG, masking etc. I'm keeping a very open mind, and would also like to know about Zanpars route to diagnosis and treatment, as I have noticed his/her posts elsewhere.

The study is interesting because there is this point in PD and in B12 def where it becomes difficult to use l-dopa/B12.They seem to be in a remarkably similar place, so do these genes fulfill several purposes. I don't know enough to even know if that is possible, but I like learning