If I read this right, it sounds like PDers have a gene which preclude them from being able to take B6 from food and make it bioavailable....this is critical because B6 is a prerequisite/precursor to dopamine production.

Interestingly, I have always wondered why the B vitamins, in particular B6, are said to interfere with PD drugs, notably sinemet?

Here's the link: http://www.sciencedaily.com/releases...0115182627.htm

This is very interesting. You know now we can buy the activated pyridoxal version of B6. It is called P5P, and is available OTC.

There is also a corresponding lack of SAMe in the brain of PD patients. This means lower neurotransmitter synthesis too.

http://www.sciencedirect.com/science...7e1416dd1f5a81

http://www.ncbi.nlm.nih.gov/pubmed/11104210

1. Clin Sci (Lond). 1979 Jan;56(1):89-93.

Niacin depletion in Parkinsonian patients treated with L-dopa, benserazide and
carbidopa.

Bender DA, Earl CJ, Lees AJ.

1. Benserazide and carbidopa, decarboxylase inhibitors used in the treatment of
Parkinson's disease, have been shown to inhibit the enzyme kynurenine hydrolase
in rat and mouse liver. This results in reduced synthesis of nicotinamide
coenzymes from tryptophan, and hence an increased reliance on dietary niacin. 2.
Pellagra might be expected as a result of this inhibition of endogenous synthesis
of nicotinamide nucleotides, but has not been reported in patients treated with
either drug. 3. The urinary excretion of N1-methyl-nicotinamide, a product of
nicotinamide nucleotide metabolism, is considerably reduced in patients treated
with dopa alone or in combination with an inhibitor of peripheral dopa
decarboxylase, to as low as 40% of the control value. This means that many of
these patients could be classified as 'at risk' of niacin deficiency, even if not
frankly deficient. 4. Patients treated with dopa plus a decarboxylase inhibitor,
but not those treated with dopa alone, also show a reduced excretion of
xanthurenic acid, and an increased excretion of kynurenine, as would be expected
after inhibition of the kynurenine pathway, and possibly indicative of marginal
vitamin B6 deficiency.

PMID: 477187 [PubMed - indexed for MEDLINE]

My apologies for mixing Vit B3 and B6, but if you will pretend that we're discussing B vitamins in general....

The study that I just posted indicated that sinemet could really lower niacin (B3) levels.

Wikipedia says- Currently, niacin deficiency is rarely seen in developed countries and is usually apparent in conditions of poverty and malnutrition and chronic alcoholism[9]. Alcoholic patients typically experience increased intestinal permeability leading to negative health outcomes. Studies have indicated that in patients with alcoholic pellagra, niacin deficiency may be an important factor influencing both the onset and severity of this condition .

That implies that, by wasting niacin from the body, sinemet may lead to leaky gut and thus increase toxic load in the bloodstream.

Finally, there is this -
"Effects of oral niacin on endothelial dysfunction in patients with coronary artery disease: results of the randomized, double-blind, placebo-controlled INEF study."

The study is here

Basically it says that under certain conditions of abnormal cholesterol that niacin can beef up the endothelium for coronary patients. And, of course, the BBB is endothelial tissue as well.

So, it is a little convoluted, but it just might be that sinemet induced loss of niacin could open up the BBB?

I wouldn't be surprised. Most drugs we use today have the potential for making things worse in the long run, while appearing to fix things in the short run.

BTW I have a B6 thread on Vitamin forum. I just added this PD information to it and bumped it up. If you are interested I've collected some interesting data on it.

Historically I brought P5P to the net on BrainTalk back in 1999 or so. It is interesting that it has become more popular and understood since then. I use the NOW brand BTW from iherb.

is catalyzed by the enzyme aromatic amino acid decarboxylase (AAAD). This enzyme, as do many other enzymes involved in the metabolism of amino acids, has an absolute requirement for pyridoxal phosphate as a cofactor. As Rick has pointed out, DOPA medications contain carbidopa or benserazide to inhibit this enzyme in the peripheral tissues, so that the administered circulating DOPA will have a better chance of making it across the BBB, and thus be available to the AAAD in the dopaminergic neurons for dopamine synthesis.

Pyridoxal phosphate is synthesized by the enzyme studied in the Science Daily article. That enzyme, pyridoxal kinase (PDXK), appears to be decreased in neurons of some people with PD, but not in otherwise healthy people.

I have not yet read the article in the original literature, but my guess is that this is a unique neuronal form of PDXK that has decreased activity or is not present at normal levels in brains of the affected people.

It is interesting to note that AAAD is also responsible for the conversion of 5-hydroxy tryptophan to serotonin. Further, dopamine itself is an intermediate in the synthesis of norepinephrine and epinephrine. In addition, pyridoxal phosphate is an essential cofactor in the enzyme glutamate decarboxylase which converts glutamic acid to gamma amino butyric acid, GABA, which is still another important neurotransmitter. Thus, a deficiency in conversion of pyridoxal to pyridoxal phosphate by PDXK in the CNS could do all kinds of mischief.

I hope to get to my office at the university on Monday where I can get to the original article. I may get a PDF of it for anyone who may be interested.

Robert

This is awesome, I think I may actually understand part of this thanks to your explaining it as you did. I'd love to see the PDF as well, thanks much.

http://www.thehealthierlife.co.uk/na...oke-00411.html

Robert- I would like to see that pdf if you can get it. Thanks.

It seems rather odd that the things we are warned to avoid for the sake of sinemet are often the very things we need to exercise what capabilities we have to produce it. These two B vitamins and the amino acids I know of, but can't help but wonder if there are more.

Looks like a lot of us want to see that PDF. When I first started researching supplements, I looked into B complex vitamins and SAME. Heck, SAME is super-expensive and contraindicated for those of us on levodopa. So what exactly gives, is it possible to take a B complex and SAME but spaced apart from med dosages? Anyone taking SAME?

Laura