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Beyond 23 & Me Testing

Discussion in 'Genetic Testing and SNPs' started by Journeyman, Nov 30, 2016.

  1. Journeyman

    Journeyman Senior Member

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    Hi Folks,

    It's been over 3 years now since I got my 23&Me results, and I'm not happy with my energy/mental state in spite of devoting a lot of time and money to what should be the appropriate supplements to address my SNP's. I'd like to know where to from here to better understand why my interventions have thus far not yielded the results I was hoping for.

    After consistently taking Methylation supplements for the past 3+ years I've now been off them since mid September and am keen to find out how my body is functioning in its 'natural' state.

    It seems that Organic Acid Testing in the form of a Genova NutrEval Diagnostic Panel would seem the best course of action as I really feel that RichK was onto something with that Glutathione Depletion Cycle theory about CFS, but is this the best option? Perhaps theres better testing options available now or similar but at lower prices from other providers?, or indeed one thats better for Australian residents??(eg: where will I get my blood drawn for Genova so they get a fresh sample when I'm in Australia??)

    I've also taken a moment to read through Caledonia's NutrEval Interpretation guide and can't help but wonder about my ability (even as a partially university educated student in this area) to appropriately interpret the results even if I do get the test, and am considering an integrated doctor to interpret/provide advice. Does anyone know any excellent functional medicine practitioners in Sydney, Australia that appreciate the significance of methylation etc. like the rest of us???

    I look forward to your suggestions,

    Regards

    Journeyman
     
  2. Hip

    Hip Senior Member

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    That's the experience of most people on this forum, that knowing their SNPs and taking supplements that supposedly compensate for them leads to little or no benefit. Treating based on your SNPs sounds pretty scientific, but the reality seems more pseudoscience than anything else.

    You might want to consider treatments for ME/CFS that have been validated in published studies.
     
    Last edited: Dec 10, 2016
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  3. alicec

    alicec Senior Member

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    I think we need to put SNPs in proper context. Much of the internet chatter that convinced people that they had serious mutations which were causing their health problems is of course nonsense. But that doesn't mean they are of no value.

    Some people may indeed identify one or more SNPs which have serious consequences and so addressing these could make a big difference to health outcomes.

    For most of us though we find a collection of things which have small effects and which at best could be making a contribution.

    I see these as potential weak points. When we are healthy and eating well they don't matter much - our bodies can compensate.

    Put the system under pressure, such as during illness, and maybe these weak points might start to matter. My approach has been to shore up the weak points where possible as a kind of preventative exercise.

    I don't see this as offering any cure, rather it is trying to offset the possibility that these SNPs could be an issue.

    The NutrEval test is one of the better ones for trying to gain insight into weaknesses and blockages in various metabolic pathways. Results reflect the totality of metabolism and show our functional status, something that is influenced by far more than just SNPs.

    When you order the test you will be given a form to take to a local pathology company for the blood draw.

    You need to collect the plasma and whole blood samples from them and ship along with the urine sample according to instructions.

    Please note it may not be possible to get results from the tests on RBCs. The long shipping of whole blood to the USA is very likely to result in haemolysis and rejection of the sample. They will send you the wherewithal to repeat this part of the test but it will probably fail also. There is no getting around this.

    Here is an Australian company which acts as an agent for Genova. You need to get a practitioner to order the test - not necessarily a doctor. Many naturopaths and chiropractors use NutraPath. They should be able to help with interpretation but breadth of knowledge is obviously going to vary with individuals.

    It may be possible to order directly from Genova but you will still need to have some sort of ordering practitioner. You should be able to find this info on their website.

    There are other possibilities - eg Genova Ion Panel (also blood and urine) or urine only organic acid tests (OAT).

    If you decide on the latter I suggest you order the test from Great Plains Laboratory. OATs are much the same but the GPL test is unique in looking at three oxalate markers. Oxalate issues are a distinct possibility in any condition involving prolonged oxidative stress, so is something people with CFS/ME should be aware of.

    You don't need a practitioner for this test - you can order yourself from the website.

    Please note that the urine kit is the same for various tests - you can order several from the same sample, provided you supply sufficient volume. This will save on shipping costs if you happen to want a few tests (eg I have ordered an OAT, urine amino acids and urine metals on the same sample).
     
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  4. Journeyman

    Journeyman Senior Member

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    Alice its clear from your advice that you think about the effect of what you are saying at each step . As I acted on your response post to look up and choose the service whenever I ran into queries your next line invariably had the answers. A big kudos to you for your meticulous advice - its really appreciated. It's like you can read minds !? .-)

    Getting the Genova NutrEval done via Nutripath is $1010 here in Sydney so I'll probably make the order once I muster the courage for my credit card... I can't get the Great Plains site to load, however if I were to choose the special OAT's test they offer that includes what I assume to be everything Genova test plus the oxalates??? then it will be much cheaper? Again will I need to find an Australian lab service?? Above All: What results would I be missing that I would otherwise be getting if I ordered the Genova test via Nutripath??

    Thanks in advance for your valuable advice...

    Journeyman
     
  5. alicec

    alicec Senior Member

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    The Genova test does look at more things than the OAT alone. Here is the overview from Nutripath. The Genova site would undoubtedly tell you the full detail of the analytes. Basically it includes an OAT (though not extensive as most stand alone OATS), plus plasma and urine amino acids, plasma fatty acids, some oxidative stress markers and RBC minerals.

    Here is a list of the GPL OAT test. Basically it is a more extensive OAT than you get with the Genova test but you don't get any of the plasma or RBC tests, nor all of the oxidative stress markers.

    It is quite a bit cheaper and you don't need anyone to order it, you can do so yourself from the website. If you can't get that link to work just try goggling GPL OAT. It is an easy test to order and they send you results by email. There will be some interpretation but essentially you have to work out details of what it means for yourself.

    The Genova test is more comprehensive and is probably a better place to start but as you have found, it is expensive. If this is just too much money you would still get a lot of useful info from the cheaper GPL OAT.

    There is no one ideal test. If you can afford it the Genova test might be a good place to start as a one off. For ongoing checking of progress you could use the GPL OAT at whatever intervals the pocket can bear.
     
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  6. Journeyman

    Journeyman Senior Member

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    I was meaning to order the Genova test today but I realised that a lot of the important stuff that we need can come from the OAT, and at $249 its a far more attractive option than the Genova ($1010 here in Aus) Having said this I'm still not sure about which to order as I really fear that if I go the GPL route I'll end up needing some results only the Genova one offered....

    I've looked at the sample report from Genova here https://www.gdx.net/core/sample-reports/NutrEval_Plasma-Sample-Report.pdf
    to try and distinguish whats tested in their plasma and RBC which might be absent in the GPL test. From what I can tell its mainly the various types of fatty acids such as your Omega 3 to Omega 6 balance, and I'm pretty confident this isn't an area I need help with as I've years of good cholesterol test results done through the normal health system and eat a very strict diet supplementing with Flax Seed Oil, Fish oil etc. etc.

    So is it accurate to surmise that the only thing I'm missing out on (given my comfort with EFA's) would be the Oxidative stress markers???... which admittedly would seem quite important for anyone who has an absent GSTT1 SNP, a hetero SHMT01 and a bunch of defective CYP detox enzymes (vulnerable to xenoestrogens and plastics which proliferate our world since 1960s)

    Or am I missing something here such as the fact that Genova tests amino acids through both urine and blood which acts as a great failsafe should the result of one be ambiguous?

    I mean in terms of understanding your bodies performance in methylation (which is at the core of everything in terms of immunity, mitochondrial function etc.)) isn't it based primarily on the OAT results?. For example I recall RichK making reference to someones OAT interpretation with a heavy focus on Formiminoglutamic Acid (FIGlu) and Methylmalonic Acid as if these were really what it was all about... Is it fair to say that given I'm fairly comfortable with my essential fatty acid metabolism, that I'll get pretty much everything I need from the GPL OAT test?? (And save $750)

    PS - Have just checked exactly what the GPL OAT test which is now combined with Urine and I can't see that it includes FIGlu???

    Thanks as always for your assistance Alice (and whoever else wants to add their 2 cents)

    Regards

    Journeyman
     
    Last edited: Dec 2, 2016
  7. alicec

    alicec Senior Member

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    Also the plasma amino acids and RBC minerals, but as I already noted, you might not get results for the minerals because of technical issues.

    The OAT is equivalent to the first part of the Genova test - what they call metabolic analysis markers.

    Here is a sample report from GPL so you can directly compare.

    There are some oxidative stress markers - not a direct estimate of glutathione as in the Genova and not the marker for lipid peroxides and DNA oxidation (8OHdG), but indirect estimates of glutathione status and of CoQ10.

    Plasma and urine tests give a somewhat different angle on metabolism.

    Stuff in the blood reflects what is going on right now. High and low values might reflect excess and deficiency but alternatively high values for something might reflect that it is not being used well (decreased metabolism), low values that it is being used too much (increased metabolism).

    Urine reflects what has happened over a longer time and shows downstream metabolism. High values might reflect that a particular pathway is being pushed (high metabolism) while low values might mean a pathway is being underused (low metabolism).

    These are just general consideration. Interpretation of high or low values depends on the metabolite. For some, and these are usually noted on an OAT, high urine values mean an enzyme is not functioning well, allowing something which should be processed by that enzyme to accumulate. In turn the poor enzyme function reflects the absence of some cofactor.

    MMA (B12 deficiency) and FIGLU (folate deficiency) are examples of this.

    The GPL OAT uses different folate markers (uracil and thymine).

    As you have noted, the considerably cheaper OAT gives a lot of information. The Genova test does give more info but whether it is worth the big difference in price is hard to say.

    You could search the Nutraeval tests for things which cover just a small part of the Genova extras - eg the oxidative stress markers.

    It all really depends on you, what you most want to know and how much you want to spend.

    Forgot to say previously that you need to add shipping costs to the GPL test. This would be about USD 75 for them to ship the collection kit to you and for return of your sample by courier.
     
    Last edited: Dec 2, 2016
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  8. Journeyman

    Journeyman Senior Member

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    The real question then is how useful the GPL 'indirect' measures of Glutathione really are compared to the direct markers... Considering RichK's great Glutathione depletion theory, I think its pretty important that I get truly useful values for Glutathione - otherwise its not worth measuring..

    Is it the case that even if a persons results showed a high MMA level or a high FiGlu that theres still some uncertainty as to the real cause of the problem?? If this is the case then wouldn't the plasma values be used to fill in the puzzle? So, if for example if a persons FiGlu was high from the OAT results and the Plasma/Blood Folate levels were high then I would be in a better position to resolve the cause of the problem than if I just had the high FiGlu result from a standalone OAT right? (Would be able to deduce that it was a functional deficiency rather than a nutritional deficiency)

    Again, similar to the query regarding the indirect glutathione measure in the GPL test, how useful are these FiGlu alternative measures, Uracil and Thymine. From my first year studies in molecular biology I'm guessing the link between folate and Uracil and Thymine is a tenuous one at best meaning it would be far less useful for predicting a functional folate deficiency than a FiGlu proper. Is this a fair assumption to make??

    I've just been analysing this http://www.functionalmedicine.net/pdf/Insider's%20Guide_37.pdf great resource so as to understand the potential importance the absence of one or more of the measures in the GPL OAT might be compared to the Genova test:
    One thing I really want to know is whether I've got Kryptopyrrole disorder (might explain the constant nervous tension in spite of consistent Zinc and P5P supplementation) and it seems that I'd need the test to include a measure for Xanthurenate which the GPL OAT lacks... or is there some 'indirect' measure that I could piece together with my SNP info from 23&Me results and make a fairly informed deduction about this illness being possible...?

    Again thanks so much for your insights on these tests and helpful advice. I really feel I'm close to being able to make an informed decision now and just want to let you know its massively appreciated Alice

    Regards

    Journeyman
     
    Last edited: Dec 4, 2016
  9. Valentijn

    Valentijn Senior Member

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    The existence of a pyroluria-related disorders is hypothetical. Hence there certainly hasn't been any genetic research showing any links to it.
     
  10. alicec

    alicec Senior Member

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    Very difficult to answer that question. The indirect markers are specific to metabolic pathways involving glutathione. The pyroglutamate marker is shown in the Genova test also. This pathway recycles glutathione.

    The 2 OH butyrate marker is a byproduct of the transsulfuration pathway which produces cysteine, the rate limiting element in glutathione synthesis.

    Both pathways increase when more glutathione is needed.

    I was just giving examples of the various considerations needed to evaluate markers. Not all markers follow the same pattern.

    The MMA and FIGLU markers are well accepted markers of deficiency of B12 and folate respectively. These markers only increase if the relevant enzyme is not functioning well. This could be due to a genetic defect in the enzyme but these are extremely rare; much more likely to be problems with supplying sufficient cofactor (this can be more complicated than frank deficiency).

    Plasma folate and B12 measurements may be helpful in revealing frank deficiency, but there is also the phenomenon of high values in face of functional deficiencies (as evidenced by high MMA and homocysteine). This suggests some sort of processing/uptake problem.

    So yes the two measurements together may give some insight but ultimately it is the functional test that reveals what is going on in cells.

    No it is direct. Folate dependent enzymes are involved in purine and pyrimidine synthesis.

    I haven't seen any comparisons of the reliability of the two sets of markers but the GPL markers are quite valid. There is something about the ratio of the two markers which might give further info but I'm afraid I've forgotten what it is. My once excellent memory now lets me down frequently.

    You might find this thread interesting.
     
    Last edited: Dec 4, 2016
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  11. caledonia

    caledonia

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    I've been down this path - here is where I'm at.

    If you've gotten all the B vitamins and various nutrients worked out with little improvement, take a look at certain methylation cycle diagrams and you'll see that mercury and lead inhibit methylation at methionine synthase. These metals are very powerful, and it would likely be pretty difficult to take enough methyl supplements to overcome their influence.

    Then take a look at the Kreb's cycle diagram in the Nutreval test. If you have low values in the cycle (probably if you have fatigue), you'll see that mercury, arsenic and fluoride are inhibitors of the Kreb's cycle.

    If you interpret your Nutreval with the compilation of Rich Vank's interpretations you mentioned above you may see metals coming up again and again, even if the metals blood test results themselves come out low.

    In addition to that, because I take notes in a medical journal over time and go back and review things occasionally, I noticed that my thyroid recovered from autoimmune thyroiditis and many other positive changes happened a year and a half after I got my last mercury filling out.

    Then whenever I tried to chelate (the wrong way as I now know) I got worse.

    Rich Vank's glutathione depletion theory fits in with mercury as it causes glutathione depletion (and many other issues at the cellular level).

    I'm now chelating with Andrew Cutler's frequent dose chelation protocol, which is the only way I suggest chelating. I found out I have mercury, lead and arsenic.

    See the Cutler section my signature link for more info on testing and treatment. Testing is under $100 so it's more or less a no brainer, even if you don't think you have mercury.

    There are many people on the Cutler forums who sound just like us on here (I think this is where many of the undiagnosed are), and many people are getting better.

    If I had it to do over and knew what I know now, I would have started on this sooner.
     
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  12. Journeyman

    Journeyman Senior Member

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    I've had the chance to watch the William Shaw video on interpretation of the GPL test and whilst he sounds quite slow he went on to suprise me with his insights into Clostrida and numerous other aspects of the test, and did a good job highlighting the importance of each. It left me feeling that they couldn't possibly have left out something that would give a good indication of Glutathione status, and given what you're saying re: the 2 OH Butyrate marker together with the Pyroglutamate marker, I can't help but thing that these two should give me some very good insights into my Glutathione status. It really would be good to find out how valid indicator they are for sure though. After all as well designed as the GPL test is for detecting gut dysbiosis related bacteria etc., Glutathione might just not be high on their priorities for whatever reason...

    I think we can rule out any concern then about the test lacking a FiGlu marker since the alternate measures seem suffice which is great......

    Yeh I see what you mean, though I also note the post by someone who seems qualified in biochemistry who in spite of agreeing with the lack of evidence, was finding positive effects in treating it with his own child.... Sometimes existing medical knowledge can be quite lacking and might not explain the why, but the positive outcomes in the face of treatment confirm the existence.... Nonetheless I won't be pinning my test choice on which offers a measure of urinary pyrroles... interesting read.


    So now the only remaining question is how useful the DNA oxidative stress marker
    is 8-keta something??? - a-Ketoglutaric Acid ? and the lipid peroxidases….. As a person who suspects they’ve had some periods in their life of both heavy metal toxification, xenoestrogen intoxication, and impaired B12/Folate how much importance should I give to these oxidative stress markers.


    PS – I note from the GPL OAT sample report that it just says ‘Malonic’. Please tell me this is just a shorthand reference for methylmalonic….?


    Thanks as always for your detailed advice Alicec…. I’m almost ready to choose the test J
     
  13. Journeyman

    Journeyman Senior Member

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    I suspected heavy metal toxicity back in 2008 and already by 2009 I had embarked on a pretty consistent process of chelating for Mercury, Aluminium, Copper and some others. I called on a number of online resources and employed FIR Sauna's once a week over a period of like 2 months to rid my body of any potential mercury. I even took the precaution of getting a hair mineral test done prior the sauna program and after it. I was looking for the change in these various metals between the two tests (spread apart by 6-9 months from memory) In comparing the two HMT's It was the case that mercury increased along with a couple other metals, but in both the starting HMT and the second HMT, the values for any of the metals were never that high to begin with, so yes there was some chelation caused, but it turned out I never had much of these metals in any event..

    I do now wonder having revisited the Cutler protocol after reading your post whether I used sufficiently strong chelating agents compared to agents such as DMPS etc. which were difficult to obtain at the time. However I think I did because IIRC FIR Sauna's are one of the best means of chelating metals like mercury, and I even went to the extent of regularly using a combination of Chlorella followed by raw Cilantro (coriander) leaves 20 mins later (apparently this is a super mercury chelation package) so I think I nipped it in the bud. I was concurrently taking lots of curries full of turmeric and black pepper over those years too so I think whatever got chelated would have got removed as well as reasonably possible... So what do you think - were these chelation methods quite powerful for mercury??? or do they pale into insignificance when considered against the DMPS agent....

    This is my concern with getting the GPL OAT rather than the Genova. Its one thing to get a good variety of markers tested, but this is only going to be as useful as the interpretive guides that I can find to go with it... Having said this I guess I've already learnt enough from this thread (Thanks AliceC) to simply substitute markers that RichK might refer to as FiGLU and instead relate them to my Uracil/Thymine results, and similarly use my pyroglutamatic acid marker reference when he refers to Glutathione levels....

    Thanks for coming in on this thread... I've actually been basing my current plan of action based on your signature link guides...

    Regards

    Journeyman
     
  14. caledonia

    caledonia

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    @Journeyman

    I hate to tell you this, but there is a high chance you still have metals.

    I have gone through the same thing of thinking I've chelated and finding out it was not effective. There is a lot of bad information out there.

    The FIR sauna is ok and probably actually did some good.

    For the hair testing, the levels of the metals are mostly not relevant. Your test can show low mercury, when it's actually high.

    What you're looking for is deranged mineral transport. If you took a hair test that included mineral levels, you can go back and get them interpreted with Cutler's interpretation. (see the Cutler section in my signature link).

    As far as chelators, the chlorella and cilantro are too weak. What they do is pull out some mercury, then drop it so that it recirculates back in the body, causing more symptoms.

    The correct way is to use the chelators ALA, DMSA and/or DMPS and to dose them in weekly rounds on their half life, which is every few hours, day and night.

    Then the length of time that you chelated is probably not nearly long enough. If you're sick enough to be on this site, figure on at least 1- 2 years. They told me I was very toxic with multiple metals and to expect 4 years of chelating to get it all out. I've seen some people who have chelated 5 to 6 years - they have gotten very much better.

    Here is a good summary of what not to do:
    http://cutlersuccessstories.weebly.com/what-not-to-do.html
     
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  15. caledonia

    caledonia

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    @Journeyman

    As far as the OAT vs. Nutreval, you can use Richvank's interpretation for the parts where they test the same things. It's a lot of hunting and pecking, but it can be done.
     
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  16. alicec

    alicec Senior Member

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    They definitely test methylmalonic.

    Regarding direct glutathione testing, Nutrapath offers this as a stand alone test.
     
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  17. Journeyman

    Journeyman Senior Member

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    I'm interested to understand what this term deranged mineral transport means, and how its measured. When I did these two hair mineral analysis tests (which included all the toxic metals) spaced apart by 6-9 months I revisited the 2nd results looking for the change in the metals (not their pure magnitude). Is this change whats referred to as the deranged mineral transport????

    With regard to chlorella and cilantro being weak I suspected that to be the case compared to DMPS etc. but even if thats the case, wouldn't DMPS do the same thing you suggest Cilantro/chlorella to be doing. That is, chelating it into mainstream circulation where it simply goes to another location. If not can you explain how DMPS chelates differently?? Doesn't the Chlorella help absorb/bind up the now released toxic metals??
    I should point out that I also took Turmeric and lots of sulfur containing foods so that once chelated the toxic metals (if indeed there were any) would be bound up for excretion rather than re-deposited...

    Thanks for the link to the cutlersuccessstories - I'll bookmark it pending my OAT results that might tie a few things together...

    Regards

    Journeyman
     
  18. Journeyman

    Journeyman Senior Member

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    I couldn't find it as of a few days ago but I trust it exists and will make use of it should my GPL OAT leave some questions unanswered. I really do feel its a far better value test than the Genova option given that whatever few things it lacks are made up for by the inclusion of the oxalates, and I can always use Nutripath for the standalone Glutathione test should I get really curious.

    I just realised looking at my Sig block that Glutathione is probably a very important thing for me to test, though it would be good to know what significance the absence of the GSTT1 SNP is in terms of the bodies Glutathione levels. Does it mean I have 50% less than the average joe with the normal SNP for example?? If anyone could shed some light on this it could be very helpful....

    Lastly one thing thats recurred to me a number of times on revisiting this thread is how much do urine samples degrade during the 1-2 days of international transit that will take place from the time I post my sample... How significant could this degradation be on the validity of my results, and which amino acids are most sensitive to the likely temperature and time effects the transported sample will experience....
    Moreover how could I obviate this risk. (When I did 23 & Me for example I drove it to the airport rather than a subsidiary courier point)

    Thanks again to all for your input on this thread - particularly you Alicec!
     
  19. alicec

    alicec Senior Member

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    The absent call means that you supposedly have a deletion of the gene. Actually this is quite common. About 20% caucasians have this deletion. In general this is compensated for since there are many members of the GST superfamily.

    It is possible that the deletion could be a problem in combination with other SNPs.

    However I would check your 23andme raw data. As this thread notes, 23andme don't specifically test for the deletion, and test only a few alleles on the gene. If you have any SNPs listed in your results then you do have the gene.

    Most organic acids are stable. A few such as alpha-keto acids and I think pyruvate and succinate are somewhat unstable.

    This is largely overcome, I believe, by immediately freezing urine and shipping with cold pack according to instructions.

    To make sure urine is properly frozen, particularly when I have been shipping a fair volume, I have collected on Sunday morning and arranged courier pickup for Monday. I specify afternoon pickup just to narrow the time window that the sample is out of the freezer.

    I believe all OAT tests use this method so if there were any deterioration, all would have the same problem. As far as I know laboratories seem to be satisfied but you could ask GPL. They are usually good about responding to queries.
     
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  20. Horizon

    Horizon Senior Member

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    I think the organic acid tests aren't entirely helpful because what are we comparing to? We don't have enough reearch. If it is simply based on raising glutathione, why not save the money on tests and focus on boosting glutathione?
     
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