Functional Genomic Analysis

Functional Genetic Analysis in Mast Cell Activation Syndrome and Histamine Intolerance

When you have Mast Cell Activation Syndrome or Histamine Intolerance, Functional Genetic Analysis is one of the most powerful tools we have available today.

Genetic testing is one of the most important tools I use in my practice to get results for clients. This is along with other functional labs and a very comprehensive intake process.

Functional Genetic Analysis is very complex but provides an incredible amount of information about you.

Unfortunately, many practitioners don’t have extensive training in Functional Genetic Analysis. And take a simplistic approach to genetic interpretation. This often leads to misunderstandings and making the wrong supplement recommendations.

Have you been given really high doses of methylfolate or methylB12 that made you feel bad? Or other supposed supplements to “fix” your genetics that backfired?

If so, this article will help you understand why that approach doesn’t work. And will teach you how to find someone who can do a really good job of analyzing your genetics.

In this post on Functional Genetics in Mast Cell Activation Syndrome and Histamine Intolerance, you will learn:

  • What are genetics?
  • What is Functional Genetic Analysis?
  • Why is genetic testing and Functional Genetic Analysis important if you have Mast Cell Activation Syndrome or Histamine Intolerance?
  • Why you shouldn’t immediately start methylfolate if you have MTHFR variants
  • Other misunderstandings in Functional Genetic Analysis, especially around Mast Cell Activation Syndrome or Histamine Intolerance
  • What are Epigenetics and Genetic Expression?
  • What you need to know about genetic testing if you have Mast Cell Activation Syndrome or Histamine Intolerance

Before we go on though, I should tell you why I’m qualified to write this article.

How I Got into Functional Genetic Analysis

I’ve been working in the field of Functional Genetic Analysis since 2012.

That is a long time in this area. Back then, we were looking at around 60 different genetic variants. That provided a lot of health clues for many people, but things have grown exponentially since then. Now I’m analyzing well over 10,000 variants! That’s 166x the data we had in 2012!

I was one of the first two people to get certified in Functional Genomic Analysis, a very in-depth and comprehensive program. I’m also a Research Advisor for the Nutrigenetic Research Institute, which is an amazing think tank of genetic practitioners.

I’m immersed in Functional Genetic Analysis on a daily basis. In addition, I teach about Functional Genetic Analysis to other health care practitioners and Functional Medicine Doctors at conferences and online.

In a world where anyone online can claim they are an expert, it can be hard to separate fact from fiction.

There are many people who write about genetics online who don’t have a good understanding of it, even if they’ve been writing about it for a long time.

Many people take a very limited, reductionist view of “if you have X variant, you have to do Y.” For example, many practitioners start people on methylfolate if they have MTHFR. But many times this backfires.

I wish it could be that simple. But it isn’t. As my good friend and expert in the field, Dr. Bob Miller, says – this is more like 3D chess played underwater. It is really that complex.

So, this article is about bringing you the best information about the field of Functional Genetic Analysis, especially for when you have Mast Cell Activation Syndrome or Histamine Intolerance.

I want you to have this info in case you are running your genetics or asking someone to analyze it for you.

Because having your genetics analyzed properly may very well make or break whether you get well.

I’m going to explain everything in lay terms, instead of a lot of technical detail, to make it easy for you to understand. I want you to get the info that is most important for you to be able to get well.

Ok – let’s get started!

What You Need to Know About Genetics When You Have Mast Cell Activation Syndrome or Histamine Intolerance

Your genetics are basically the blueprint for your body. You have over 20,000 genes. Your genes are made up of what is called DNA.

The DNA is made of what are called base pairs that encode all the instructions to make you.

The DNA is a double helix and the base pairs are like rungs of a ladder linking the two sides of the helix. These base pairs are designated by one of 4 letters – A, T, G, or C. These are called nucleotides.

Your genes provide the base instructions for proteins that build everything in your body – all your enzymes, your cells, your tissues, your organs. You inherit your genes from your parents.

For almost all the nucleotides, you get one base pair copy from your mom and one base pair copy from your dad. For example, for the gene AOC1 that codes for Diamine Oxidase (the DAO enzyme to break down histamine), you might get a C from one parent and a C from your other parent.

If you get what are considered 2 normal copies of a gene, it is said to be the normal genotype. But changes are very common in genetic code. This is what make us unique.

Genetic changes are called variants. Gene variants are sometimes called mutations, but that has a negative connotation.

I like to use the word variant instead. This implies that it is variant from the normal genetic code. And that variant can have benefits or can create problems. Or it can do both!

Now, going back to the AOC1 gene example for Diamine Oxidase. If you inherited the CC genotype for AOC1, you would have the normal genes.

However, let’s say you got a C from one parent and a T from another parent. The T is called a risk allele. This means the T can cause changes in how the Diamine Oxidase enzyme is made.

It can make it harder for your body to break down histamine through this Diamine Oxidase pathway. This is called a single variant or a heterozygous variant.

Now, what if you got a T from one parent and another T from your other parent on the AOC1 gene? This is called a double variant or a homozygous variant.

These variants are also called SNPs which stands for Single Nucleotide Polymorphisms. This means there can be multiple changes (polymorphisms) on a single nucleotide (the rungs of the double helix DNA ladder).

These SNPs can potentially cause significant challenges making the Diamine Oxidase enzyme.

So here are my gene variants for Diamine Oxidase. I have a single heterozygous variant on the 2nd gene. You can see I have a C and a T:

ABP1 variants Mast Cell Activation Syndrome Diamine Oxidase Mast Cell 360

Here is an example of someone with more variants who has even more significant Histamine Intolerance:

ABP1 variants Mast Cell Activation Syndrome Diamine Oxidase Mast Cell 360 2

Read more: What is Histamine Intolerance?

What Is Functional Genetic Analysis for Mast Cell Activation Syndrome and Histamine Intolerance?

Functional Genetic Analysis is more than just looking at SNPs. Functional means focusing on what is happening underneath your symptoms and why they are happening.

Functional Genetic Analysis is about looking at your genetics to get an indication of why things might be happening.

And here is one of the biggest and most important distinctions:

Functional Genetic Analysis is about understanding that SNPs are only about genetic predisposition. It means that just because you have XYZ variant, it isn’t necessarily a problem.

For example, if you have the BRCA1 or BRCA2 variants associated with breast cancer – this does NOT mean you will get breast cancer.

I had a client who contacted me and was terrified about her breast cancer risk. She had been told that if she had BRCA1 or BRCA2 variants, she had to have her ovaries removed.

Other people have had proactive mastectomies just because they had these variants. But it isn’t that simple. What really scares me is that people are getting very invasive and risky surgeries that are often unnecessary. This is because of these gross oversimplifications and reductionist thinking. This trend frightens me.

Here is the truth. For more than 99% of genetic variants, it is about the interplay of your genetics with everything else that happens in your life, such as:

Here is a map of the genes involved in Breast Cancer. After looking at this, how can we base risk on just 2 genes?

Genes interactions in breast cancer Mast Cell 360

Image Source:

You don’t have to understand this map. I just want you to see that there is so much to it. This is why Dr. Bob Miller calls it 3D chess played underwater.

So, in a nut shell, Functional Genetic Analysis:

  • Views genetic variants as predispositions, not diagnostic
  • Always interprets variants in the context of lab testing, symptoms, health history, and family history
  • Explores the upstream and downstream factors of genetic variants
  • Explores the effects of the interplay of different variants
  • Explores the multitude of factors that affect the gene expression
  • Weighs which genes are clinically relevant
  • Understands that genes still being researched often still have clinical value
  • Applies genetic analysis to developing individualized support protocols

So the lesson is:

It isn’t about if you have X gene you have to take Y supplement. We have to look much deeper. Functional Genetic Analysis is about understanding the many factors involved in how your genes affect your health.

Why Are Genetic Testing and Functional Genetic Analysis Important If You Have Mast Cell Activation Syndrome or Histamine Intolerance?

If it is so complicated, why get genetic analysis at all? I get emails every week from people who ran their 23andme data but said they never knew what to do with it.

This information is so powerful, it is a unfortunate to have that much knowledge about your body and not be able to do anything with it.

People also send me genetic reports that list only 60 variants – this is honestly the dark ages compared to where we are now. We can sequence the entire genome now. We don’t know what it all does yet, but we can get it. And we do know what many, many genes do.

When you have Mast Cell Activation Syndrome or Histamine Intolerance, it is really important to get Functional Genetic Analysis.

I’ve said before I spent well over $100,000 seeing over 50 practitioners before I started to turn the corner. Functional Genetic Analysis was the key to that for me. Here are just a few things I got insights on that made a huge difference:

  • Why I was getting inflammation and insomnia from curcumin
  • Which 3 of the histamine degrading pathways could be affects
  • Why L-glutamine for leaky gut gave me bad anxiety
  • Root factors related to my Mast Cell Activation Syndrome
  • Factors affecting my sleep
  • How to address all these things

Of course, I had to pair the genetic information with labs and symptoms to wade through what variants were affecting me. This is what I do every day in the office for clients too.

Most health care practitioners aren’t able to make the time to study Functional Genetic Analysis in depth. It literally takes years of dedicated study to learn this area. This is fine for practitioners who have clients with minor health issues.

But when you have chronic health issues like Mast Cell Activation Syndrome or Histamine Intolerance and a lot of sensitivities, it is crucial to have in depth analysis.

In fact, not having this information is like trying to read your roadmap to health with big pieces of the map missing. You are missing a lot of the information!

Before we had Functional Genetic Analysis, I kept chasing my tail trying to get well. And nothing was working. It would have cost me so much less money if I’d had Functional Genetic Analysis then. I want to save you all those expenses and wasted time I had to go through.

So, if you have Mast Cell Activation Syndrome or Histamine Intolerance, you need to get Functional Genetic Analysis to learn what your genetic predispositions are for things like:

  • Issues with the 3 histamine degrading pathways
  • Factors that impact mast cell activation
  • Issues with the many different detoxification issues
  • Issues with methylation
  • Root factors that can contribute to inflammation

To get well, you want to combine the power and knowledge of Functional Genetic Analysis with:

  • A very comprehensive health history and symptoms analysis
  • The right labs that you need
  • The right foods for you
  • The right exercise for you
  • The right supplements for you
  • The right stress management for you
  • The right lifestyle changes for you

This is the secret to the success I get with my clients. This is what you are looking for when you have Mast Cell Activation Syndrome or Histamine Intolerance. These are the keys to unlocking your health and getting your life back.

Misunderstandings in Most Genetic Analysis That Are a Big Problem When You Have Mast Cell Activation Syndrome or Histamine Intolerance

The biggest misunderstanding in genetic analysis I see today is thinking, that if X then give the person Y.

Remember that big map above for the breast cancer gene? Well, “if X then Y” thinking doesn’t work to understand that map. So, “if X then Y” thinking is called linear thinking.

But you have to use systems thinking to do Functional Genetic Analysis and apply what is seen on the breast cancer genes map to help someone. Systems thinking means looking at how the entire system works together.

But a lot of health care practitioners struggle with systems thinking and can only use linear thinking. And that is what I see in most genetic analysis approaches, even by some really famous people and by big genetic companies.

Misunderstandings About MTHFR, Especially Around Mast Cell Activation Syndrome and Histamine Intolerance

Here is one of the most rampant examples. This is about methylation genetics.

So, if you have read much about genetics, you have likely read about methylation already.

Methylation is a very important process in the body where a type of compound called a methyl group gets attached to other compounds in your body. That methyl group is very, very important.

Methylation is involved in these things in your body:

  • Manage gene expression and DNA repair
  • Reduce inflammation
  • Immune response
  • Support healthy neurotransmitter functioning
  • Modulating inflammation
  • Detoxification
  • Energy production
  • Reduce histamine levels through one of the histamine reducing pathways

You can see this is a really important pathway!

I have many clients come in thinking their methylation is broken because they have an MTHFR variant. People often will start by telling me about their genetics and that they have MTHFR. They get really worried this is a major problem.

This simply isn’t true for most people. Here is where these MTHFR myths came from.

So, MTHFR was one of the first functional genes to be researched and discussed in the world of genetic analysis.

The MTHFR gene codes for an enzyme that converts folate to an active form of folate called 5-MTHF to help support methylation.

What happened in the MTHFR story was that many people thought they had found the genetic Holy Grail in chronic health conditions when research about MTHFR came out.

Then some people built their businesses around how to address MTHFR variants and became very attached to how important they perceived it to be. One of the most concerning things I see is when clients come in who have been put on very high doses of methylfolate because they have MTHFR variants.

This ignores 3 things:

  1. Not everyone with MTHFR variants needs methylfolate. Remember how everything comes down to genetic expression? Well, methylation and methylfolate status should be tested first.
  2. Methylfolatein higher doses can upregulate some processes in the body. These can worsen Mast Cell Activation and glutamate issues. It isn’t the right supplement in everyone. It may also increase some cancer risks.
  3. MTHFR variants have to be looked at in context of the entire methylation. You can’t isolate out functional genetic variants like many people are doing with MTHFR and other variants. You have to look at the entire system as a whole and what is happening upstream and downstream.

To understand the context of this issue, look at this map just on what is involved in folate. I circled the MTHFR enzyme in green so you can see it in context. You don’t have to understand the map, I just want you to see how complex this really is.

MTHFR and Folate Map Mast Cell 360 Mast Cell Activation Syndrome

Image Source:

Do you see how many other genes are involved? Some of these may even compensate for MTHFR variants. Nothing is simple in the world of genetics.

The good news is we now know that MTHFR is not as concerning as it once was thought.

There can be some health issues with MTHFR variants in some people. But some MTHFR variants can be protective for some health issues too. It is all about knowing how to interpret the data.

What you should know is that MTHFR doesn’t even make my top 20 list of genetic variants that I see involved in Mast Cell Activation Syndrome, Histamine Intolerance and other chronic health challenges.

If you have MTHFR, don’t fret. Just get your methylfolate tested and have someone look at a Methylation Profile test for you.

However, there are some variants that are often VERY relevant for my clients with Mast Cell Activation Syndrome or Histamine Intolerance. Here are just a few:

  • AOC1/ABP1 variants for Diamine Oxidase – even single variants
  • BCMO variants to make retinol, the active vitamin A
  • H1, H2, H3, H4 variants
  • NQO1 variants, which affects detoxification
  • ATG13 Autophagy variants
  • COMT variants for breaking down neurotransmitters and methyl compounds

So, those are just a very small handful of the 10,000+ variants I’m looking at in my clients with Mast Cell Activation Syndrome or Histamine Intolerance.

Genetic Expression and Epigenetics in Mast Cell Activation Syndrome and Histamine Intolerance

Let’s talk more about the genetic expression again. Because I really want you to get this.

Your genes are not a life sentence. Genetic data gives you your blueprint for your body, but what is even more important is the way the genes are expressed. This is what is called epigenetics.

Epigenetics involves the interaction of your genes with your environment. Basically, all of these things affect your genetic expression or epigenetics:

If you think of your DNA as the blueprint of your body, you can think of genetic expression like the builder of a building.

The builder can read the blueprint (your DNA) and replicate the mistakes in the blueprint when building the building.

Or the builder may be at the top of his/her game that day from great sleep, good food, the right supplements, and correct the mistakes in the blueprint while building the building.

Or the builder may have had a rough night, have eaten junk foods, had a couple drinks, and make new mistakes that weren’t in the original blueprint.

This is a basic metaphor for how genetic expression and epigenetics works. This genetic expression happens through RNA.

Pretty much anything you can think of affects genetic analysis. This is why we can’t say if you have MTHFR you definitely need methylfolate. More than 50% of my clients have MTHFR variants.

When I see those and some other methylation variants, I simply recommend we check folate and a Methylation Profile. For some people, the cellular levels of folate look good and the Methylation Profile is optimal. That tells me the genetic expression is a more important factor than even the genetics alone.

So, if you have any genetic variants, they don’t mean they are definitely causing an issue for you. This is why Functional Genetic Analysis has to be thoughtfully interpreted in the context of your symptoms, your health history, your labs, and everything in the list above to determine how much of an issue that variant is for you.

This is complex work, which is why most practitioners haven’t been able to take the time to become fully trained in it. It is something that takes a lot of passion and dedication to become skilled at.

Just make sure you work with someone who really knows Functional Genetic Analysis in and out and has been using it daily for a few years. And get an in-depth health history and symptoms analysis along with the right labs you need. This is what will jettison you on your road to healing!

The Power of Functional Genetic Analysis When You Have Mast Cell Activation Syndrome or Histamine Intolerance

So, you may be wondering, why look at DNA at all? Does it have any usefulness?

It actually has a lot of usefulness. As I said at the beginning of this post, Functional Genetic Analysis is one of the more powerful tools in my toolbox. It may hold the key to why you aren’t recovering.

Here is why. Genetic Analysis shows us where the predispositions are in your body. While that doesn’t mean you necessarily have an issue there, it tells us we definitely need to go check on those areas. Often it shows us areas we never would have discovered otherwise.

In Mast Cell Activation Syndrome and Histamine Intolerance, you are probably getting a sense from reading this, its about how many possible root triggers there are. If you haven’t read my Mast Cell 360 – 7 Most Common Root Causes Report, you can get it here:

Click Here to Download Your FREE Mast Cell 360 Guide: 7 Common Root Causes in Mast Cell Activation Syndrome!

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Find out the underlying issues that commonly cause Mast Cell Activation Syndrome and get a better understanding which ones are affecting you.

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So, back to how genetics can save you a ton of time and money getting your health back.

One major root issue in Mast Cell Activation Syndrome and Histamine Intolerance is anything that creates inflammation.

There are hundreds of reasons you could have inflammation in your body. Looking at the genetic analysis with the right labs helps me narrow those possibilities down from hundreds to a manageable handful. Then we can check on and address that handful in a systematic way.

But if we didn’t have Functional Genetic Analysis, we would have to look into all the possible causes of inflammation, starting with the most likely and working down the list until your inflammation is resolved.

That process works ok for the general public, but many of my clients have already tried those processes with other practitioners and didn’t get better or even got worse.

This is often because those of us with Mast Cell Activation Syndrome or Histamine Intolerance frequently have more rare genetic variants that are rarely looked at.

Functional Genetic Analysis can help catch issues that may have never been thought of without looking at your DNA. Once again, the important thing is that the DNA has to be taken into context with your symptoms, health history, and labs.

For clients with Mast Cell Activation Syndrome, these are some of the critical genetic pathways that I analyze in a Functional Genetic Analysis:

  • Gut weaknesses
  • Histamine degradation
  • Mast cell activation
  • Glutamate
  • Oxalates
  • Energy production
  • NADPH production
  • NADPH oxidase
  • MTOR/autophagy
  • Phase I detox CYP450s
  • Phase II detox glutathione
  • Phase II detox sulfation
  • Phase II detox methylation
  • Phase II detox glucuronidation
  • Phase II detox acetylation amino acid conjugation
  • EMF sensitivity
  • Nitric oxide
  • Heme pathway
  • Signalers NRF2/KEAP1/SIRT1/SIRT3/SIRT5
  • VDR vitamin D
  • BCMO involved in vitamin A

If you have Mast Cell Activation Syndrome or Histamine Intolerance and your Functional Practitioner is looking at your DNA – make sure your practitioner understands those pathways and how to look at them in context of your individual health history, symptoms, and labs.

Functional Genetic Analysis can guide your practitioner to making the right supplement choices for you and getting the right lab testing. Often Functional Genetic Analysis reveals major missing pieces for people who keep falling through the cracks in healthcare.

What DNA Kit Should You Use If You Have Mast Cell Activation Syndrome or Histamine Intolerance?

The best genetic kit available for those with Mast Cell Activation Syndrome at the time of this writing is Functional Genomic Analysis.

It’s an at home saliva kit. This kit can be purchased through a practitioner for comparable costs to the 23andme kits.

You want to run the Functional Genomic Analysis kit through the practitioner you want to interpret it for you.

Your Genomic Resource Kit available at Mast Cell 360 for Mast Cell Activation Syndrome and Histamine Intolerance

I unfortunately can’t recommend 23andme anymore. They were bought by the large pharmaceutical company GlaxoSmithKline.

At that time of purchase, they dropped over 7,000 very important variants related to Mast Cell Activation Syndrome and Histamine Intolerance.

If you are lucky enough to have the version 4 23andme data, then you still have all the relevant variants. To check if you have version 4, look for v4 in your 23andme raw data filename. Here are the instructions for downloading your 23andme raw data file.

If you have 23andme version 5 data, then you don’t have the complete picture. Version 5 is missing some of the critical genetic variants involved in Mast Cell Activation Syndrome.

This is why I recommend people who haven’t run their genetics yet use Functional Genomic Analysis.

What About Epigenetic Testing for Mast Cell Activation Syndrome or Histamine Intolerance?

The new leading edge of Functional Genetic Analysis is epigenetic testing. This allows you to see how your genetic expression is changing over time. The idea is that you test your epigenetics to get a base line. Then you make some changes and test again 6 months later to see how they are working.

I’m always interested in the cutting edge. And I’m watching this field as it grows out of infancy into something very useful for clients.

This area isn’t a replacement for Functional Genetic Analysis. It won’t give us that minute level of detail at this point in time. But, I do see it as an excellent adjunct to Functional Genetic Analysis of the DNA.

The company in the lead on this currently is Chronomics. They are looking at epigenetics in the areas of diet, sleep, environment, social interactions, exercise, and wellbeing.

This will help you and your practitioner see how well your protocol is working in these different areas. Then you may be able to see progress even before your symptoms have gone away to make sure you’re on the right track.

I also see this to be absolutely game changing for parents of non-communicative children on the Autism Spectrum.

This is very exciting stuff. I’ll be testing my own epigenetics with Chronomics in the next couple weeks. I’m testing out the technology and usefulness to see how this could help my Mast Cell Activation Syndrome and Histamine Intolerance clients as well as those with other chronic health issues like Autism Spectrum Disorders. I’ll keep you posted on what I learn!

The Bottom Line on Functional Genetic Analysis in Mast Cell Activation Syndrome and Histamine Intolerance

Functional Genomic Analysis is crucial to success when you have Mast Cell Activation Syndrome or Histamine Intolerance. Function Genomic Analysis looks at your genetic predispositions along with symptoms, health history, and labs to develop individualized support protocols that actually work for you.

It is important to work with someone who truly understands Functional Genomic Analysis because this area is very complex.

Linear thinking, that is, if you have X variant you should take Y doesn’t work. For example, it doesn’t work to say if you have MTHFR variants, you should take methylfolate.

Getting Functional Genomic Analysis may be the game changer in turning around your health when you have Mast Cell Activation Syndrome or Histamine Intolerance. You want to have 23andme version 4 data or Functional Genomic Analysis data.

Epigenetic testing may be the next new big thing. But it isn’t a replacement for Functional Genetic Analysis. Think of it as an adjunct with exciting new information to unravel your health mysteries.

Have you had your genetics tested? What were your big AHA moments? Tell me in the comments below!

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  1. Sandra Reed

    Beth, just read all about DNA testing. I
    Hope we can work together on my DNA analysis. I have not taken yet.

  2. Corinna Kennedy

    I was so excited to see you mention that curcumin actually makes you inflamed. My MD always insists on IV Curcumin and I always react with almost instant heat — even at the testing dose which he sticks to with me. He will not accept that I inflame from it, even as I turn red and practically tear the needle out of my arm. However, no where in the article does it say anything about how or why this occurs. I was so hoping for information on this because Googling it gets me nowhere except how fantastic Curcumin IS for inflammation. Being different leaves us in the dark.

    1. Jamie, Mast Cell 360 Team

      Hi Mel, Some of the ancestry DNA testings have limitations. Beth prefers to use Functional Genomic Analysis which is a practitioner only company but provides a more comprehensive picture in regards to health. Another direct to consumer options you may consider is The DNA Company. You can use coupon code MASTCELL360 for $50 off the Genetic Sample Collection + DNA 360 Report:

  3. Amie

    Hey Mel, just wondering if there’s any Canadian companies you could recommend? Thanks so much!

    1. Jamie, Mast Cell 360

      Hi Amie, You may want to check out The DNA Company and see if they can send to Canada. This is a direct to consumer option and you can use coupon code MASTCELL360 for $50 off the Genetic Sample Collection + DNA 360 Report:

  4. JULIE

    Yes! Got mine at and doing exactly what this article talks about. Refusing to be shut up on double mutated items just because they haven’t been studied. Their database and search engine for your genome is amazing.

  5. Tina

    If I get this ordered is this something that I can get an appointment with you to read it, I, a rubics cube🤷‍♀️since young ruptured appendix 14 rhogam shots ruined veins sneeze with sugar, alcohol, if I eat to much, been floxed 8 years ago, don’t run fevers tested positive for fructose malabsorbtion, folic acid thru thru the roof, not sure where it is now, I gave up on drs.

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