Genetic Testing and Organic Acids Testing: A Dynamic Duo of Diagnostics

Today I have two words for you:  Personalized medicine.  What does this phrase mean to you?  When I think of personalized medicine I think of treatments that are custom designed for each individual patient, and I believe this is the ultimate goal for all of us in the field of functional medicine.  To make this happen, we will have to work together as a team - the healthcare practitioner, the lab, and the patient.  If we do so effectively, the result should be better health and improved lives of our patients.  The only way to get there is to design a treatment plan that addresses the underlying cause(s) of our patient’s ailments and not try to just suppress the symptoms. 

When I talk to both practitioners and patients, they often ask “Where do we start?” or “What is your most important test?”, and until recently I would have always said that the Organic Acids Test (OAT) is the obvious place to start.  The reason for this is that the OAT provides more information than any other test.  The OAT gives us a metabolic snapshot of multiple pathways in the body, offering insight into possible underlying causes of symptoms, as well as what kind of nutritional support is needed.  However, now the OAT by itself is no longer the obvious choice.  I am now recommending the OAT + GPL-SNP1000 combo because these two tests, one metabolic and one genetic, work so well together.   Today I would like to share some of the markers in each of these tests that work really well in tandem.    The primary pathways where we see overlap between the two tests are methylation, mental health, detoxification, and oxalate metabolism. 

The first pathway that GPL-SNP1000 covers is the DNA methylation pathway, also called the MTHFR pathway.  This pathway is a process by which carbons are added onto folic acid from amino acid and redistributed onto other compounds throughout the body.  This process is responsible for the formation of methionine, S-Adenosyl methionine (SAMe), and thymidylate monophosphate (dTMP).  These compounds are then used in neurotransmitter metabolism, detoxification, nucleotide synthesis, and multiple other processes.  I can’t say enough about how important neurotransmitter metabolism and detoxification of chemicals are to everyone’s health.  We have so many patients for whom the majority of their symptoms result from the upset of these two processes.  Since the methylation pathway is so important we decided to make it a high priority in our new genetic test.   GPL-SNP1000 looks at 105 different methylation SNPs (single-nucleotide polymorphisms).   Next week I plan on going more in-depth on the methylation pathway and how GPL-SNP1000 can be useful.

So what markers in the OAT are important for patients with MTHFR mutations?  The first one we have is vitamin B12.  We evaluate B12 levels by measuring the amount of methylmalonic acid (see Figure 1).  B12 is an important cofactor for many of these methylation enzymes.  The second important marker is pyridoxic acid, which is a form of vitamin B6. I have counted over 50 enzymes that require B6 in the body.  It is an important cofactor in the methylation pathway.  It is directly involved with the function of CBS enzyme and indirectly involved with MTHFR, BHMT, and SHMT.  Another marker involved with the MTHFR pathway is uracil.  Having an elevated uracil level can be indicative of folate pathway malfunction.

The next pathway that is helpful to analyze in both the OAT and GPL-SNP1000 is the mental health pathway, which involves the synthesis and breakdown of neurotransmitters in the brain.  The combination of measuring the neurotransmitter metabolites and knowing if the enzymes involved are functional will help guide us to the best treatment options.  GPL-SNP 1000 covers 14 different mental health genes, which I will cover next week (I’m trying not to make these blog posts too long).  Three of the best markers in the OAT for measuring neurotransmitter metabolism are homovanillic acid (a dopamine metabolite), vanilymandelic acid (epinephrine/norepinephrine), and 5-HIAA (serotonin, marker).  These markers are the metabolites of the neurotransmitters by the enzymes MAOA and COMT (see Figure 2), the genes for which are analyzed in GPL-SNP1000.  Deficiencies in these enzymes due to faulty SNPs  may cause low neurotransmitter levels, which may also be caused by low amounts of precursors, cofactors, or increased inhibitors which is why information from both the OAT and GPL-SNP1000 is so incredibly useful.   

The third pathway that I will briefly touch on today is the detoxification pathway, and specifically for glutathione (GSH).  Detoxification is so important in today’s industrial, polluted, and toxic world.  Every day we are inundated by hundreds of chemicals.  We are exposed to many through the environment and some by choice (like medications).  Our bodies have to process these chemicals in some way.  GPL-SNP1000 looks at dozens of genes that are important for detoxification.  A good marker in the OAT for how well the body is detoxifying is pyroglutamic acid.  Elevated values of pyroglutamic acid are indicative of glutathione deficiency due to excessive toxic exposure or a genetic issue. 

The final pathway I’m going to discuss today is oxalate metabolism.  Oxalates are crystalline molecules that we absorb from our diet (high oxalate foods) or are produced by an infection, like yeast/fungal overgrowth.  These oxalates can accumulate in the body and cause inflammation.  The symptoms of oxalate accumulation include pain, nephrolithiasis, and neurological symptoms. Oxalates are known to cause/create kidney stones.  Children with autism who exhibit eye-poking behavior have been shown to have a build-up of oxalates behind their eyes, causing tremendous pain, and thus the eye-poking.  GPL-SNP1000 covers five different genes involved with the production and elimination of oxalates.  The OAT has three oxalate markers:  glyceric, glycolic, and oxalic acids. (Figure 3)  In addition, low B6 and increased yeast or fungal markers are associated with increased oxalates. 

I think that is all I’ll cover today.  In the future I will cover the methylation pathway and the neurotransmitter pathway a little more in-depth.  If there is another pathway you want me to cover in greater detail, please let me know.  I want to be a part of your healthcare team as we all work together for the better well-being of our patients.

Email gplblog@gpl4u.com if you have any questions about this blog post.