Pharmacist Steve

[Kathi49]

Steve,

Just wanted to say I had a slight talk with my Geneticist friend last night over the phone. It was really short but she did explain a bit more about the CYP450....metabolizing that is. She said my Neurologist could run a test specifically for that but that it is expensive. So, I asked her, okay, let's say I don't have a test and I am deficient anyway, and she said just go to a lower dose or cut the meds in half, etc. And that's what I have been doing pretty much all along anyway. She mentioned she is deficient in it and can't take Sudafed as an example, at all. She told me she is wired for days if she does.

So, I started reading more on this again. I don't quite understand the "Inducers" or "Inhibitors" as this gets very deep...more complex as you stated earlier. I do NOT know what all those numbers mean LOL!

Anyway, it is all pretty interesting and I would love to have that test done...just not sure if my Neuro would be for it or not. It would be nice to know though.

[mrsdoubtfyre]

Here is a website you might find interesting:

http://www.dnadirect.com/patients/tests/drug_response/ethnicity_and_drug_metabolism.jsp

This chart is easier for me to understand, so you may like it too.

http://www.healthanddna.com/drugchart.html

This is a pretty complex concept, so don't be surprised if you doctor doesn't "get" it.

We are moving however, in this direction, in the hopes that in 10 yrs drug therapies will be individualized for each patient for each genetic difference.

One thing that is happening in a parallel fashion is understanding that vitamins, minerals and other nutrients in the diet do not have a one dose fits all for people either. Already we see errors in metabolism for folate and B12 that significantly lead to illness and deterioration for some. The dehydrogenase family is also affected genetically. Dr. Ames who designed the Ames test for carcinogenicity believes that the Bcomplex family is filled with genetic variation, and that is very close now to being clarified.

So as drug treatments become individualized, I expect to see nutrient needs addressed the same way.

[Pharmacist.steve]

Steve,

Just wanted to say I had a slight talk with my Geneticist friend last night over the phone. It was really short but she did explain a bit more about the CYP450....metabolizing that is. She said my Neurologist could run a test specifically for that but that it is expensive. So, I asked her, okay, let's say I don't have a test and I am deficient anyway, and she said just go to a lower dose or cut the meds in half, etc. And that's what I have been doing pretty much all along anyway. She mentioned she is deficient in it and can't take Sudafed as an example, at all. She told me she is wired for days if she does.

So, I started reading more on this again. I don't quite understand the "Inducers" or "Inhibitors" as this gets very deep...more complex as you stated earlier. I do NOT know what all those numbers mean LOL!

Anyway, it is all pretty interesting and I would love to have that test done...just not sure if my Neuro would be for it or not. It would be nice to know though.

CYP450 is a area where collectively what we don't know dwarfs what we do know. This area became a discussion point about 15 yrs ago.. and this well is very deep

[Kira]

One thing that is happening in a parallel fashion is understanding that vitamins, minerals and other nutrients in the diet do not have a one dose fits all for people either. Already we see errors in metabolism for folate and B12 that significantly lead to illness and deterioration for some. The dehydrogenase family is also affected genetically. Dr. Ames who designed the Ames test for carcinogenicity believes that the Bcomplex family is filled with genetic variation, and that is very close now to being clarified.


As someone who has gone through the gamut of tests for metabolic disorders of all sorts, I agree with this. I have had so many different metabolic labs done over the past couple of years when they were trying to pin down which metabolic disorder I have (turned out to be Complex I Deficiency with secondary defects in Complex III & IV as well as fatty acid oxidation... in other words, mitochondrial disease).

Basically, any enzyme/pathway that exists in the body can show genetic variation... although some defects in certain enzymes/pathways are not compatible with life. Whether or not the mutation results in disease/symptoms depends on how badly the enzyme's functioning is affected, and how badly our cells need the product of the affected pathway.

For example, if you only need 80% of the ATP made by healthy mitochondria for your cells to function normally, then a mutation that decreases mitochondrial ATP production to 90% of normal shouldn't result in disease. But if your mutation decreases mitochondrial ATP production to 30% of the normal amount, then you'll be pretty sick.

It works this way for many pathways... our cells often produce more metabolites than they need to get by, so a little variation in enzyme function doesn't show up unless you specifically look for it. Since a lot of variation is asymptomatic, it gets passed from generation to generation. There are so many potential diseases related to mutations in metabolic pathways, because any enzyme/pathway can "break."

When I was getting tested to try to figure out which metabolic disorder was giving me rhabdomyolysis all of the time, several specialists said over and over again that it was very possible that they wouldn't figure out what particular metabolic disease I had, since we just plain don't know how to test for all of the stuff that can potentially go wrong.

As far as variation in B-vitamin metabolism goes, some of my labs incidentally showed mild accumulation of certain metabolites that build up when something is wrong with a pathway that involves folic acid. Not enough to count as a full-blown metabolic disorder, but enough to show decreased enzyme activity somewhere in that pathway.

Knowing about that is good reinforcement for me to remember my B-vitamins every day (some of which I take in pretty high doses, according to recommendations from my metabolic doc and metabolic nutritionist).

Interestingly, my mom started taking folic acid about a year before we knew about my metabolic issues. Subjectively, it made her feel noticeably better (cognition, energy, etc), and she kept talking about how great it was. At the time, I didn't think too much of it, but figured it wouldn't hurt her and left it at that. Now, though, we are pretty sure that my mito came from her side of the family, and think that maybe the folic acid issues came from her side, too. Anyway, she and I both seem to have mild trouble with that pathway, and taking extra folic acid seems to help.

I did want to say that I'm not suggesting everyone run out and get boatloads of metabolic testing done unless there is reason to suspect a metabolic disorder (a "broken" enzyme, not a vitamin deficiency). It's fairly common for docs to check various vitamin levels when you have issues like neuropathy, anemia, etc... but those aren't the labs I'm talking about when I say "metabolic testing." I'm talking about specialized blood and urine tests for organic acids which aren't even offerred at a very many labs, which are usually checked when a metabolic/genetics doc is trying to diagnose a specific metabolic disorder. These labs are also pretty hard to interpret if things start coming back positive, so you really do need the right doc to order them or they won't know what to do with you when they come back funky.

Anyway, just wanted to comment on this because I think it's interesting.