(wanted to make this a separate topic. most of the articles have appeared in foreign journals. Our neurologist has never mentioned the need to supplement with B12 and folic acid. Has anyone on this forum been advised to use these with Sinemet? thanks, madelyn)

folic acid and B 12
there are a number of studies noting use of supplements Vitamin B 12 and folic acid in instances of B 12 deficiencies to decrease homocysteine levels that result from use of Levodopa. Levodopa reportedly interferes with folate metabolism and B 12 function.

Parkinsonism Relat Disord. 2008;14(4):321-5. Epub 2007 Dec 4.
Folate and vitamin B12 levels in levodopa-treated Parkinson's disease patients: their relationship to clinical manifestations, mood and cognition.

Abstract
We tested the hypothesis that mood, clinical manifestations and cognitive impairment of levodopa-treated Parkinson's disease (PD) patients are associated with vitamin B12 and folate deficiency...Levodopa-treated PD patients showed significantly lower serum levels of folate and vitamin B12 than neurological controls, while depressed patients had significantly lower serum folate levels as compared to non-depressed. Cognitively impaired PD patients exhibited significantly lower serum vitamin B12 levels as compared to cognitively non-impaired. In conclusion, lower folate levels were associated with depression, while lower vitamin B12 levels were associated with cognitive impairment. The effects of vitamin supplementation merit further attention and investigation.
PMID: 18055246 [PubMed - indexed for MEDLINE]


The influence of levodopa and the COMT inhibitor on serum vitamin B12 and folate levels in Parkinson's disease patients.
...Our findings show that levodopa-treated Parkinson's disease patients have low folate (p < 0.0007) and vitamin B12 levels (p < 0.0003). They also demonstrate that the addition of a COMT-i to levodopa + DDC-i treatment causes lower serum vitamin B12 (p < 0.03) and folate levels (p < 0.005) than levodopa + DDC-i treatment alone. We suggest supplementary treatment with vitamin B12 and folic acid in these situations.
http://www.ncbi.nlm.nih.gov/pubmed/17565222

Neurol Neurosurg Psychiatry 2003;74:549 doi:10.1136/jnnp.74.4.549
Correspondence
Benefit of folic acid supplementation in parkinsonian patients treated with levodopa
T Müller, D Woitalla, W Kuhn
+ Author Affiliations

Department of Neurology, St Josef Hospital, Ruhr University Bochum, Gudrunstrasse 56, 44791 Bochum, Germany
Correspondence to:
 Dr T Müller; 
 thomas.mueller@ruhr-uni-bochum.de
We read with interest the recent excellent review by Reynolds on the role of folic acid and the risks and benefits of its supplementation in the nervous system.1 It emphasises the beneficial importance of folate on the numerous methylation processes in combination with S-adenosylmethionine (SAM), which donates its methyl group to prevent hyperhomocysteinaemia.1 However SAM deficiency, which is associated with, for example, cognitive decline and/or mood disturbances, and increased total homocysteine levels, which support onset of vascular disease, may also caused by drugs, for example, levodopa.2,3 Levodopa is administered with dopa decarboxylase inhibitors (DDI) to prevent its peripheral degradation. This increases conversion of levodopa to 3-O-methyldopa (3-OMD) by the ubiquitious enzyme catechol-O-methyltransferase (COMT) in blood, peripheral tissues and in nigrostriatal neurons.2,3 COMT requires Mg2+ as cofactor and SAM as methyl donor. Thus O-methylation of levodopa to 3-OMD is associated with conversion of SAM to S-adenosylhomocysteine and subsequently homocysteine.

http://jnnp.bmj.com/content/74/4/549.1.full

(B12 supplement should be "under the tongue" or sublingual form. stomach acids render an oral form useless.
For those individuals who have had DNA profiling, check for polymorphisms of the methylenetetrahydrofolate reductase (MTHFR C677T), methyltetrahydrofolate-homocysteine methyltransferase (MTR A2756G), and 5-methyltetrahydrofolate-homocysteine methyltransferase reductase both associated with folate metabolism and in addition, check (MTRR A1049G and C1783T) associated with processing of B12 in the bodY. If you have mutations in the MTHFR gene, must use a breakdown product of folic acid, methyl folate, and folinic acid if one has the other mutation. Mutations in MTRR requires a B 12 supplement.

Well... I am not an expert on PD and B vitamin metabolism.

It seems that SAM has been documented low in PD patients for a LONG time. Whether that is causative or a result, I've never seen documentation about.

This quoted article is in error however about B12 being rendered ineffective by stomach acids!
This is just an example of a scientific paper that is totally lacking in truth on this one detail. There are many papers showing that oral B12 works very well... as long as it is taken on an empty stomach so food will not compete for absorption once it gets to the small intestine. The acids in the stomach DO NOT degrade B12 at all. I don't know where that author gets that!
In fact sublingual is really suspect, since the cobalamin molecule is so huge it can't cross the small area of the mouth effectively.

This is only one medical reference (recent) to explain how oral swallowed B12 can work:
http://neurotalk.psychcentral.com/post834583-5.html

It is best to use methylcobalamin --- in 1mg to 5mg doses daily on an empty stomach, for best results.

It is true to use methylfolate in those with the DNA polymorphism however.

I think PD is complex....very complex. So I tend to refrain from commenting about PD supplements. PD may be different for different patients, or we just don't know enough.

I'll interject this PQQ information..about mitochondrial decay and using this supplement to prevent it here. Anyone know about this? It just turned up on our PN forum:

http://en.wikipedia.org/wiki/Pyrroloquinoline_quinone

SAM is part of a complex methylation cycle. It normally gives up its methyl group (provided by glycine or TMG) in the body.

My Drug-Nutrient Depletion handbook lists for Levodopa and the combo Levodopa/Carbidopa that SAM and potassium are depleted with long term use.

When SAM gives up that methyl group for whatever reason, it is recycled back to homocysteine. Hence for people taking extra SAM in the form of SAMe supplement it is recommended to take
B12, B6 and folate as insurance to prevent SAM from raising homocysteine. (in all people using it)

This is the methylation map I found once and keep in my favorites:
http://www.heartfixer.com/AMRI-Outco...yl%20Cycle.htm

Of course, B6 is not recommended for people using levodopa, and that has been a long term recommendation. So I don't know where that leaves homocysteine regeneration issues?

And carbidopa itself , reacts with 5-HTP to cause a scleroderma like condition of the skin... 5-HTP is made in the body from tryptophan and B6 and magnesium. So some sources list this combo as serious and to be avoided.

So this is why PD and some supplements become a murky situation IMO. For those not using levodopa at all, the question is moot.

I'm into the habit of giving myself a B12 shot right before I have to do something challenging and/or tiring. It really does help. I mentioned it to my neuro and he just kind of nodded and said that I probably couldn't od on it cause the excess would just roll right back out.

You can do the same thing with oral. Just take it every day.

If you get some responses from injection, you may be low or borderline low.

5mg a day on an empty stomach for 3 months, then 1mg daily or 5mg twice a week.

It is now recommended for everyone over 50 to take a B12 supplement. Methylcobalamin is the best, and only pennies a day.
Available at iherb.com, Puritan's Pride and Swanson's. Not common yet in local stores. Cyano form is synthetic and requires conversion in the body, which some people fail at.

Thanks, MrsD for your info. Have saved the diagram. Husband does take FolaPro (Methylfolate), P-5-P (breakdown product of B6) and hydrocobalamin. Prior to reading the studies noting decreases in folic acid and B 12 in individuals with PD, wanted to decrease any potential hyperhomocystine. Must have read about the use of these on sites concerning mitochondrial medicine. madelyn

Mrs D, I have always been under the belief that one needs to take B vitamins together, as a complex, for optimal absorption. But if people are taking B12 by itself, on an empty stomach, and getting benefit from it, maybe that is incorrect?

Do you happen to know? I noticed you can get the B vitamins in pretty much any formulation you want, together, alone, with some but not all Bs, it gets very confusing. And everyone claims their formulation is best!

What they mean is that taking a complex is important, because some of them act as cofactors for the others. Example:
B2 in a cofactor in the enzyme that activates pyridoxine to P5P in the body. But the other B complex vits do not have the specific and critical needs that B12 does.

B12 is not well absorbed orally, and needs passive absorption in the small intestine, to work well. People with intact intrinsic factor may absorb more, but still empty stomach is essential for the B12.

And yes, one can take methylfolate if one thinks they have the MTHFR polymorphism which reduces folate availability.
There is an RX vitamin called Metanx with all 3 active B's in it, but it is expensive.

Methylfolate can be purchased in 800mcg size from Solgar OTC.
5P5 OTC from NOW brands
Methylcobalamin from several ... Jarrow, and Puritians Pride. I
just tested out the new Puritan's on myself and got high levels from testing after 3 months with 5mg daily (empty stomach). My levels were 1999! (the upper limit of the calibration where the test was done).

Most complexes do not have activated B6-- P5P. If they do they list that in the ingredients.

You can take a complex (not the Metanx one however) with food... and most people do because the complexes can cause stomach upset or heartburn.

There are only a few things needing empty stomach care...
B12 oral (also lozenge type --because you swallow the B12 dissolve in saliva)...R-lipoic acid is another.

When one takes a high dose oral B12, very little is absorbed.
1-10%. The rest is lost. There have been studies showing oral is as therapeutic as injections. I believe this is because taking it every day mimics the way we get it from food. A huge bolus every once in a while is only around in the blood for 72 hrs tops and then the rest of the time, that person is back to square one.
Doctors do not often test those patients they put on once a month injections, and this is a mistake. Many end up on these forums feeling terrible inspite of "doctor supervision" .

Was diagnosed with Pernicious Anaemia earlier this year, and doctor asked about my drug regime and whether I knew about B12 deficiency being associated with PD or PD meds!! It only took a little while to uncover a study from University of Athens Greece, as well as an article by PD nutritionist with NPDA that confirmeda connection with long term l-dopa use and PA. This study does not surprise me, though it would seem that PD like PD is little understood, and that many physicians are unaware of some of the ways it can affect patients loves. Both those references were dismissed by my GP as not significant......

You can take oral.... one does not need intrinsic factor (missing in pernicious anemia patients) to absorb passively.

Just take high dose 5mg methyl form, and on an empty stomach,and you should be okay.

Get a B12 test and/or MMA with it, to see what your level really is. Then retest after 3 months on high dose oral.

If you score like I did way over 1000, then that shows it is working for you.