Posted by Larry Hoover on January 22, 2007, at 7:54:12
In reply to talking about poor metabolizers » Larry Hoover, posted by fuchsia on January 22, 2007, at 3:56:07
> Larry, I was tested recently and I am a poor metabolizer also. I was wondering if you (or anyone else who is a poor metabolizer) are having more troubles with your health than others.
>
> I have tried so many medicines over the years and I always ended up having to take very small doses. Before it became obvious that I needed a small dose of most things I endured very severe side effects.I wouldn't say I have a greater number of health problems....I don't attribute my psych issues to 2D6 inefficiencies. I also am "Mr. Side Effect", and I also cannot tolerate typical doses of medication. Twice, side effects nearly killed me. I attribute my continued existence to my own vigilance and self-assessment skills. I am the gate-keeper of my mouth. I don't just swallow what the doctor says to swallow, any longer. I do things very carefully.
> My nerves are so bad these days (to avoid going into all my symptoms) that I can't help thinking I've been damaged by the meds and possibly the odd blast of pesticide or other environmental chemical besides.
The primary detoxicant for environmental chemicals is 3A4. I don't recall that there are any defective variants to this enzyme, and moreover, it is inducible. That means that if the toxicant load increases, so does the enzyme's activity. If you're concerned about maintaining 3A4 activity, stay away from grapefruit, as it inhibits this enzyme. St. John's wort enhances its function.
My nerves are bad (I have PTSD), but I attribute that to life history.
> I really fear I'll be one of these ones who get parkinson's as a result of dopaminergic neuron death due to chemical exposure, presuming a poor metabolizer ends up with more chemical exposure than a rapid metabolizer.
2D6 is typically a minor player in detox reactions. That said, the specific biotransformations mediated by this enzyme may play a critical role in very limited circumstances. I don't know of an environmental insult that increases the vulnerability of poor metabolizers at 2D6, off the top of my head.
> Do you know if this correlation (I've seen it written about) between an increased risk of parkinson's and being a poor metabolizer is a strong one? I've also seen an article about the increased risk of another disease though I can't remember what that was. Maybe there will be others that are picked up on in due course.
I hadn't heard of any correlations with 2D6 mutation and disease before you mentioned it, so I went to Pubmed, and took a serious look around. I find no evidence that 2D6 mutation is significantly responsible for the induction of any disease, except in very rare cases. And even then, the correlation found is not evidence of causation.
Whenever a mutation is found with some significant frequency in a population, you're going to get correlations with all sorts of other variables, simply by chance. If you examine a family cluster of Parkinson's disease, and find that all affected individuals have a poor metabolizer form of 2D6, you're likely to publish that finding. That will spur other researchers to look at their own cases, to see if the marker mutation has a similar incidence among them. When that was done, there was no evidence of any 2D6-induced vulnerability to Parkinson's. The most likely explanation, IMHO, is that Parkinson's disease only develops under the influence of multiple concurrent risk factors, one of which *might* be 2D6 low function. In a family group, it is far more likely that those other risk factors, also under genetic control, would tend to be found alongside the 2D6 mutation. In the general population, that same collection of risk factors is so uncommon, that it cannot be found in significant numbers, and no correlation is seen.
Other diseases, particularly liver disease and various cancers, have also been tentatively associated with 2D6 mutation, but once again, larger populations do not exhibit increased risk mediated by this specific defect. Breast cancer has the BRAC gene that clearly increases risk. The same does not appear to be true for 2D6.
Each of us, on average, has over 100 enzyme defects. Of course, those won't be the same ones, individually. And these are only the defects we've had the good luck to yet identify. The possible interactions of 100 or more variables approaches infinity. Which ones lead to disease? Beyond being careful which drugs and which dose I take, I'm not concerned.
> fuchsia
Nice flower. Nice name.
Lar
poster:Larry Hoover
thread:723652
URL: http://www.dr-bob.org/babble/20070119/msgs/725094.html