Posted by Larry Hoover on April 14, 2005, at 8:29:10
In reply to Re: Neuroscience tests » Larry Hoover, posted by barbaracat on April 13, 2005, at 11:36:15
> **I'm inclined to believe you, Larry, since I'm not aware of any 'breakthroughs' in neurotransmitter testing - which indeed it would be for the psychicatric community.
Indeed. If it was as simple as peeing into a cup....
> However, I have a friend who is being encouraged by the same (ex)naturopath as I to take this test. The naturopath does not have any financial interest in the two companies she's recommending and I think she'd like to believe that these tests would help.
The test itself, in my opionion, offers confirmation of the philosophy. "Believe in me, and I shall show you a sign."
> So here's my questions, just so I can display more knowledge to my friend before saying 'don't waste your money', also because my own health care providers make noises in these directions every now and then without understanding the science involved, and finally just so I can understand - mainly because there SHOULD be such a test, dammit.
>
> 1. What exactly are these tests measuring or trying to measure? amino acids? metabolites of catecholamines? valines?That's not totally clear to me, but I haven't looked *everywhere* on the site. Take the first example on this page:
http://www.neurorelief.com/index.php?major=302The first panel is a urine collection and saliva sample, said to provide analysis of: Estradiol, Estrone, Progesterone, Testosterone, Dihydrotestosterone, DHEA, Cortisol x4, Epinephrine, Norepinephrine, Serotonin, Dopamine,
GABA, PEA, Histamine, Glutamate.I needed to have my testosterone and DHEA tested, and my poor doctor was under the illusion that he needed a blood draw, under fasting conditions, at 8 a.m. And, poor man, he was under the impression that he needed to measure total testosterone, dihydrotestosterone, and free testosterone, and both DHEA and DHEA-S, all from that specially-collected blood sample.
I don't exactly know what Neuroscience is measuring, and I have no idea how they have validated their methodology. Cortisol can be measured from saliva, but it is nowhere near clear that other hormones can be, or if there is any relationship at all between saliva and/or urine concentrations and free/bound plasma levels, i.e. they can be measured non-invasively.
In the realm of neurotransmitters, again it's not clear if they measure break-down products, the metabolites, of the neurotransmitters involved, along with traces of the parent, or what. For serotonin (5-hydroxytryptamine) as an example, that would be 5-HIAA (5-hydroxyindole-acetic acid). It would be useful to determine parent and metabolite concentrations, and the ratio between them, I would think.
When I read this article, they make certain claims. When I check the references (bottom of page), the claims are not supported.
http://www.neurorelief.com/showarticle.php?NewsletterView&ArticleID=456They provide many, many references to biochemical disturbances associated with mental health disturbances, but only 3? (perhaps more) deal with urine concentrations. Not only are those references sparse, they are old (twenty years). All those older references did was confirm something we already knew, and could measure by other means. The norepinephrine metabolite normetanephrine *is* elevated in the urine of *one class of depressives*, and it turns out that class is the dexamethasone non-suppressors. I fail to see how that adds to our knowledge.
Moreover, norepinephrine has multiple metabolites (as do the other catecholamine neurotransmitters), and it would require analyses of ratios between them all, and their respective parents, to develop a true metabolic profile. That work has not been done, or at least, has never been published.
Finally, 80% of the references upon which Neuroscience itself seems to rely for its scientific rationale involve cerebrospinal fluid assessments, or blood platelet/serum analyses.
In the case of CFS, only a lumbar puncture (spinal tap) can get you behind the blood/brain barrier for a biopsy sample (that's what a spinal tap represents). It is so horribly invasive a procedure (in the sense of breaching the natural barriers of the central nervous system) that it is only done in life-threatening situations. It is done precisely because CNS biochemical profiles cannot be assessed in any other way. There is no useful correlation with the biochemical profile of CFS with any other fluids in the body.
With respect to the biochemistry of blood cells, they are employed because they float around in the blood/serum, but they are metabolically separate tissues, with their own membranes isolating them from their environment, and they are easily collected. At best, they are markers for relative rates of uptake/metabolism of some biochemicals.....but making an extrapolation to brain cell biochemistry from that of a blood cell with no nucleus, whose job it is to carry oxygen, is rather tenuous. Moreover, a *blood draw* is a rather essential requirement for this test.....as it is for serum analysis. How do they (Neurosciences) get *this* info from urine, anyway?
Mainstream medicine abandoned urinalysis for these purposes because, in my own words, "we can't really learn anything useful that way."
> 2. You mentioned that these measurments didn't necessarily show only brain neurotransmitter levels, but muscle also. Could there be a base level, no matter where those values come from, that show optimum vs. unhealthy neurotransmitter values? In other words, a specific range is the goal and let the body figure out where to put the stuff.
Urine eliminates wastes from all tissues, not just the brain. There is no way to trace a metabolite or waste product back to its source, unless you're using special radioactive substances as a probe, along with other specially controlled circumstances.
It may be that a gross measurement of urine content might indicate a systemic disturbance, but, once again, no evidence has been collected to demonstrate any relationship between urine content and mental state, but for the norepinephrine metabolite normetanephrine, and the adrenal steroid cortisol. Urine measurement of some other steroidal hormones (e.g. sex hormones) is sometimes useful, but you need to know the blood levels to complete the assessment.
> For my own curiosity, what would make this test so impossible?
It's not impossible. It's not validated. Whatever they are measuring, let us assume they are measuring it well. Modern analytical equipment can provide precise and accurate measures of chemical composition. The question is, what can we infer from those measurements?
Think about diabetic monitoring. They used to rely on urinalysis. You peed on a chemically treated swab or stick. That provided crude glucose/insulin monitoring. Then they developed home blood tests. Up until very recently, actual blood samples were analysed in portable devices.....blood tells you more than urine ever could. (I say, "up until recently", because I think they've developed portable devices that don't require a blood sample....I think I remember reading that. But still, it is a blood analyzer. A trans-cutaneous blood analyzer.)
> Neurotransmitters produce metabolites. I understand the liver passes, etc., but maybe urine is not the way to go.
Think of a full garbage truck at the dump. The garbage from each home is now blended and contaminated with all the rest. Urine is a garbage truck, except there are no "address labels" (the metaphor of the garbage truck is not perfect) as in household trash, that might let you backtrack to a particular home. Maybe you can make global statements, like "We need to control disposal of recyclables", or some such, but you can't determine who is breaking the rules.
Urine crudely records systemic metabolic processes, and only by inference, at that. E.g. serotonin that is captured by a reuptake pump is not converted to 5-HIAA. You don't know total serotinergic activity, only that which was captured by the enzyme MAO. You don't know if that chemical reaction occurred in the gut or not, or if the gut is normal (irritable bowel syndrome is serotinergic). And so on.
> If indeed spinal fluid is the only valid way so far, why aren't more doctors using these tests?
Two reasons. One, it's too invasive. It has a very high relative risk, and a life-threatening condition is pretty much the only reason for shifting the risk-benefit balance towards the benefit side. Secondly, even cerebro-spinal fluid doesn't tell us much. *It* doesn't tell us what parts of the brain might be off-balance. We can't track CFS components back to their sources, either. CFS is the garbage truck for the central nervous system.
> Barring any cost, forget the snake oil supplements, it would be a relief to do away with the medical dart board approach.
I am not saying there is *nothing* of value in these tests. It may well be that they can throw darts better after these tests than before. But, I think they exaggerate the benefit substantially, if not massively.
From a good clinical interview, you could get the same treatment objectives, IMHO, as these tests could possibly indicate.
What they offer differently from standard medical care is nutritional intervention. If you look at some of the treatment protocols, they also use SSRIs, as an example.
> I KNOW amino acid level tests do exist. Too bad it's not all about amino acids, as these guys seem to be implying. But even so, maybe amino acid levels could tell us more than we're curently getting.
Yes, amino acid levels might well be useful. That is exactly the realm I focus on.....interventions in supply management. The equipment exists. I try to make better use of it. You don't need expensive tests to begin managing supply intake.
> I'm going to to pursue this, Larry, and would appreciate any help - just point in a general direction of what would be involved in getting some useful data of neurotransmitter status.I still rely on symptoms, and symptom-specific indications. I still rely on the good old "let's do this experiment" process.
> Thanks as always for your most edifying help. - Barbara
You're welcome.Lar
poster:Larry Hoover
thread:410247
URL: http://www.dr-bob.org/babble/alter/20050414/msgs/484061.html