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This article is a brief overview of why I think the Organic Acid Test from Great Plains Laboratory is the best test for gut & methylation issues.   It is important to point out that I am not in any way affiliated with Great Plains Lab – but I do use it regularly and recommend it to many of my patients. The information below will show you how the organic acid test helps us discover the root cause of many methylation-related problems. And as many of you reading this blog are aware, not everyone who takes methylation supplements gets better. While many people find the answer to their health prayer with proper methylation support, many people may actually flare up and get worse with methyl support!  And I am committed to teaching you why that happens.

I have met many patients who performed a DNA methylation test and then were prescribed high doses of activated methyl B vitamins with disastrous consequences. If you give someone with a sour, unhealthy gut a lot of methylation vitamins, they can actually get worse! As I have pointed out in a previous post, the main reason people cannot tolerate methylation nutrition is that they have a nasty gut problem that hasn’t been addressed.

As we shall see, the gut can wreak havok on the methylation pathways we depend on for health and vitality. Patients with gut problems often experience symptoms such as anxiety, panic, worry, chronic pain, and insomnia. This group of symptoms – what I term the high-catecholamine phenotype – is very common in my practice and in our society at large.  These symptoms often start after a major life stressor – a death or divorce or illness – that triggers changes to the gut and digestion.  What worse, many people have been on multiple rounds of antibiotics (routinely meet patients who have taken over 50 rounds!) which further compromises their gut health in the face of stress.  So the key to unraveling this stress-mess problem is to recognize the role that gut microbes play in influencing our methylation cycle. Enter the organic acid test.


Organic Acid Testing

Gut microbes are always producing chemicals which have the potential to influence our methylation and detoxification pathways. The question is whether or not the population of gut bugs will be big enough or aggressive enough to have a negative effect on our methylation cycle. That is a key aspect we must understand. And luckily we don’t have to guess; we can test and know for sure. The organic acid test allows us to see exactly how much the activity of bacterial and fungal organisms is interfering with our catecholamines.

When we look at methylation problems, it is critical to understand what the gut is doing and how it can be interfering with our genetic pathways. As I have shared with you before, gut bugs create many chemicals that can irritate our sensitive detoxification and methylation pathways. When we are dealing with issues related to high catecholamines such as anxiety, panic, worry, insomnia, and chronic pain, then we must understand how the gut can make this worse. And that is precisely why the organic acid test carries so much weight in my office.


What You Get From the Great Plains Organic Acid Test

Citramalic Fumaric Glutaric (Vitamin B2-Riboflavin)
5-Hydroxymethyl-2-furoic Malic Ascorbic (Vitamin C)
3-Oxoglutaric 2-Oxoglutaric 3-Hydroxy-3-methylglutaric (CoQ10)
Furan-2,5-dicarboxylic Aconitic N-Acetylcysteine (Glutathione precursor)
Furancarbonylglycine Citric Methylcitric (Vitamin H-Biotin)
Tartaric Homovanillic Acid (HVA) Pyroglutamic
Arabinose Vanillmandelic Acid (VMA) Orotic
Carboxycitric HVA/VMA Ratio 2-Hydroxyhippuric
Tricarballylic 5-Hydroxyindoleacetic (5-HIAA) 2-Hydroxyisovaleric
2-Hydroxyphenylacetic Quinolinic 2-Oxoisovaleric
4-Hydroxyphenylacetic Kynurenic 3-Methyl-2-oxovaleric
4-Hydroxybenzoic Quinolinic / 5-HIAA Ratio 2-Hydroxyisocaproic
4-Hydroxyhippuric Uracil 2-Oxoisocaproic
Hippuric Thymine 2-Oxo-4-methiolbutyric
3-Indoleacetic 3-Hydroxybutyric Mandelic
Succinic Acetoacetic Phenyllactic
HPHPA (Clostridia marker) 4-Hydroxybutyric Phenylpyruvic
4-Cresol (C. difficile) Ethylmalonic Homogentisic
DHPPA (beneficial bacteria) Methylsuccinic 4-Hydroxyphenyllactic
Glyceric Adipic N-Acetylaspartic
Glycolic Suberic Malonic
Oxalic Sebacic 3-Methylglutaric
Lactic Methylmalonic (Vitamin B12) 3-Hydroxyglutaric
Pyruvic Pyridoxic (Vitamin B6) 3-Methylglutaconic
2-Hydroxybutyric Pantothenic (Vitamin B5) Phosphoric

Look at that list! That is 75 different markers that we can test all at once to provide insight into our important biochemical pathways. This test gives us an accurate picture of how the gut is interfering with the methylation cycle. And because this test is so useful in treating gut-methylation problems, it has quickly become my favorite.  Its true value becomes apparent once we realize how the gut bugs are able to influence our own genetic pathways.


Bacteria and Yeast Influence Methylation and Detoxification Pathways

When the bacterial and fungal populations in our gut are under control, there is only a small amount of leakage of toxins from the gut into the body. But many people who have been on multiple rounds of antibiotics and/or suffered with long-term health problems are being poisoned by the chemicals released from their gut microbes. It is critical to understand that these gut-derived chemicals can wreak havoc on our already precarious, delicately-balanced methylation pathways. This is why a test like the organic acid test is so important.

The big idea is that bad bugs in the gut will basically poop out toxins that leak into our bodies and start to interfere with our methylation and detoxification pathways. The way this works is that these chemicals – phenols and aldehydes – sit in the same parking space on our enzymes that our body was reserving for adrenalin, dopamine, estrogen, toxins, carcinogens, and more. If you have a parking space reserved for you at work, and someone else is camping out in your parking space, then you have to keep driving around looking for another one. It’s the same with your gut and your methylation pathways:

  • Gut Phenols from Bacteria – normal byproducts produced by both good and bad bacteria; healthy in small amounts. However if there is a gut infection with excess bacterial growth the phenols will begin to interfere with COMT and SULT pathways. Long-term exposure to elevated gut phenols will significantly increase the half-life of adrenalin, dopamine and estrogen. This makes individuals more prone to anxiety, insomnia, worry, panic, chronic pain and hormone-related imbalances.
  • Gut Aldehydes from Yeast/Fungi – normal byproducts produced by yeast, including Candida albicans; healthy in small amounts. When populations of yeast get too high in the gut, the alcohols and aldehydes they produce will start to interfere with Aldehyde Reductase (ALDH), Alcohol Dehydrogenase (ADH) and Alcohol Reductase (ALR). This interference will cause a slowing of detoxification of many nasty, DNA-damaging chemicals. In addition, this slowing of down of the ALDH, ADH, and ALR enzymes from yeast issues will also increase the half-life of adrenalin, dopamine, and histamine. Because of this many people with yeast issues become intolerant to stress and more prone to allergies, runny noses, histamine intolerance, etc.

Due to the similarity between the gut toxins and our own biochemistry, the phenols and aldehydes from the gut will occupy the active site of key enzymes inside our bodies. Instead of keeping that space open and available for adrenalin or dopamine or estrogen, the gut toxins will bind to that enzymatic “parking space”. When that happens the adrenalin and dopamine and estrogen are forced to stay in the circulation longer; they effectively have an increased half-life because of the toxins from the gut.

Just like you would end up spending more time in your car looking for another parking space, your body’s hormones and stress neurotransmitters will be circulating in your system longer than they should. And you don’t have to be a PhD researcher to know that you will be more stressed out and symptomatic if adrenalin is circulating in your body for longer periods of time. More is not better and that is certainly true of adrenalin!

The OAT (organic acid test) allows us to quantify and measure the chemicals produced by yeasts and bacteria, as well as other gut-derived toxins like oxalates. With this information in hand we can then determine how aggressive we need to be at healing the gut and killing bad bugs. And once the gut comes back into balance, then we have an opportunity to address deeper genetic and methylation-related issues. Its gut first, and everything else second in my book!


Oxalates, Ketones, B-vitamins and Mitochondrial Health

While looking for evidence of gut bug problems is the main reason to perform an organic acid test, it is by no means the only information you will glean. Aside from looking at bacterial and fungal metabolites, this test also will show us important information about the mitochondria, B-vitamins, ketones, fat metabolism, and even oxalate status. These biochemicals are important for us since they help determine how well our cells can produce energy and whether or not we have vitamin deficiencies keeping us from healing and growing stronger.

Oxalate problems aren’t as well-known as other health issues, but they are an important issue that needs to be addressed in many individuals. Oxalates are found in our food from both plant and animal sources. Oxalates are also produced inside our own liver from our body’s own metabolism. I won’t go into too much detail here today as I am working on another article dedicated just to oxalates, but suffice it to say that oxalates need to be removed or else they can build up to toxic levels and create biochemical issues.

The main reason oxalates are a problem is that when our oxalates go up it causes our B6 and sulfate levels to go down. Obviously sulfate and B6 are required for our body to work optimally, and lack of either one will slow down aspects of our chemistry including our detoxification system. Without adequate sulfate and B6 our body will struggle to repair itself and will be prone to low energy and chronic health problems of all types.

Many of you are aware of the fact that mitchondria provide the energy our cells need to survive – producing 94% of each cell’s energy.  Therefore we cannot support healthy brain and body function if our mitochondria aren’t working correctly.  Since the mitochondria burn fat and produce energy using B-vitamins as co-factors, its very important assess B-vitamin levels as well as ketones.  B-vitamins act like mitochondrial rocket fuel and without adequate levels, we simply cannot be healthy.  And if B-vitamins drop low enough, we may even develop life threatening diseases like pellagra and beriberi.  Obviously those diseases are rare today, but it does illustrate the importance of the molecules for our health and well being.  In many cases, especially with complex and chronic patients, there is a great value in measuring B-vitamin levels and the organic acid test covers that base very well.

Ketone bodies are also an important methylation marker that we get with the organic acid test.  When ketones are high in the urine, it means the mitochondria aren’t able to burn fat for energy effectively.  In severe cases ketosis (ketones in the urine) can be a sign of uncontrolled diabetes; but is very rarely what you will see on organic acid test.  The elevated ketones I see on the OAT has more to do with carnitine deficiency and mitochondrial problems than anything else.

I’m asked on a daily basis for good ideas on how to lose weight.  And the most obvious answer is to increase the body’s ability to burn fat.  Except without enough carnitine in the body its virtually impossible to use stored fat for energy.  It is very common for our chronic patients of all ages to have a carnitine deficiency.  In fact, methylation problems, fatty liver and high carbohydrate diets are all capable of causing a loss of carnitine from the body.  When this happens the mitochondria won’t be able to burn fat, weight loss will slow, energy will decline and ketones will show up as elevated on the OAT.



If you want to know why someone has unexplained anxiety, insomnia, panic, worry, and a host of other catecholamine-related and stress-related symptoms, then the organic acid test is the best place to start.   Once we realize that the gut has as much if not more influence on our chemistry than even our own genetic pathways, it makes sense to look there first. The OAT is the best choice because it is sensitive enough to show us problems that stool tests cannot find (many stool tests show negative fungus/yeast while the organic acid test shows them elevated). The first step to a better methylation cycle, to optimizing genes and changing lives, is to make sure the gut is healthy. And the OAT is an easy, affordable and in-depth look at that critical piece of the health puzzle.

The Great Plains Organic Acid Test provides us with an in-depth look at the body’s gut health, mitochondrial function, oxalate levels, neurotransmitter balance and B vitamins. What makes this test my personal favorite is that it allows us to understand how our gut is interfering with our methylation cycle. And as I have shown over and over again, treating and correcting gut function is the first step in the journey towards a healthy methylation cycle.



To start healing your gut quickly I recommend:

10-Day 4 R Gut Repair Program


For more videos and learning about COMT, MAO and Methylation I recommend:

Treating COMT and MAO: How COMT Influences the Brain

Treating COMT and MAO: the Hormonal Cause of Stress and Anxiety

A Genetic Cause of Pain and Anxiety – COMT, MAO and MTHFR


In Health,

Dr. Rostenberg


If you or someone you know is struggling with methylation issues and symptoms like anxiety, insomnia, depression, chronic pain, panic, worry and more, please share this video with them! For help optimizing your genes, your gut and your methylation cycle, so you may experience more abundant health in your life, you may contact Dr. Rostenberg at 208-322-7755 or