Video Transcript
Hi, this is Michael McEvoy. Thanks for tuning in today. I’m the founder of metabolichealing.com, and the lab test analysis in genetics test analysis software True Report. The web address for that is true.report. That’s true.report, and that’s what we’re looking at here today on the screen. This is the True Report website, and what this site is for is we use this to interpret genetics 23andMe raw data. These are reports that I have created and have been using in our practice and with other clinicians and colleagues for many years now.
The report is called a Nutrigenomix report and it’s based upon an analysis of over more than 300 genetic snips or S&Ps from 23andMe raw data. The other software that we have as part of this is the functional blood chemistry analyzer. This basically takes a blood test that you’ve had done and it creates an automated analysis of the blood test that tells you the optimal ranges, things that are high and low. It also gives you a variety of different patterns that get flagged, as well as different dietary, lifestyle, and supplement recommendations. These are very usable and valuable reports that we use with our own clients, as well as we have many different clinicians that use our system. We also have a client management software that this is, we use this with our clinicians and colleagues; doctors, healthcare practitioners, things like that.
What I’d like to take you through today is a review of our Nutrigenomix report. Now, many of you know that there’s been this huge surge of genetic testing in recent years that has enabled consumers, and basically anybody to have their genetics screened. The cost to do this now is come down significantly. You have a lot of different third party providers, such as myself, that have created software products that do deep analysis of certain genes in an S&Ps. With that comes different types of marketing tactics that try to get you to buy the report and tell you exactly what kind of supplements that you need to be taking and what diet you should be following.
I’ve been doing this now for about five, almost six years. From my own clinical work as a clinician, I’ve found that it’s just simply not as simple as saying, “Your genetics, you have this and this gene variation, and therefore you need to take this particular supplement.” It doesn’t come out as clean and as simple as that, and it’s simply because, as many people know, the human body is very complex and there’s many things that control gene expression as well as nutrient need and toxin load. It’s not as simple as saying one plus one equals two. You always have to look at the individual circumstances that each person has, particular symptoms, health conditions, clinical history, different lab tests that are relevant, different toxins that people are being exposed to, different infections.
There’s a lot of different variables that are influencing your gene expression, and so it’s simply not as easy as to just look at that and say, this supplement goes with this gene, et cetera. Now, as you get into the scientific literature, something that I’ve spent thousands of hours constantly, continually reading studies and having windows open on my desktop to read studies and to read the whole paper and to really look at this, there is a lot of genetic study research. Much of this research is difficult to interpret and it’s difficult to apply clinically in a relevant or meaningful way. Then, from a clinical standpoint, there are certain types of studies that are more relevant because they’ll tell you, you know, good studies will tell you that a gene is associated with a particular reduction in a blood protein marker, and those are really good studies.
The studies that have less meaning from a therapeutic standpoint are the studies that say that this snip is associated with this percentage risk of this kind of disease. Association based studies are very limited because they don’t necessarily always mean that association is causation. The other thing is that association based studies, they don’t necessarily give you any actionable information. But, good studies, and in a lot of the snips that are in my report are based on the scientific studies that talk about how a genotype will have a certain gene expression.
In other words, there are certain gene variations that have been studied that will show an elevation of a certain blood marker or a decrease in another blood marker, so these are valuable because they give you data points to track and possibly will also give you a deeper insight into certain biochemistry pathways that are relevant for you. But again, it doesn’t always mean that these things play out exactly one for one. What I’m going to take you through today are the major sections of the report, and then how this report can be used from a consumer perspective to help shed light on what your health problems might be and how this report could be helpful to understand where things may be going wrong and what you could possibly do.
This is the table of contents. All of the table of contents is clickable. If you click, for example the detoxification section, it automatically takes you to that. Then you can just simply navigate back to the table of contents. It’s all laid out in, in this table of contents. What I want to take you through is just basically category by category.
The first section is the APOE section, and the APOE genotype is based on two different genes as you see here. The genotype is potentially relevant when it comes to assessing a person’s Alzheimer’s and cardiovascular risk, primarily because the APOE 44 genotype is a considerable risk for Alzheimer’s and heart disease. That actually is one genotype configuration that can really play out significantly as an association based marker. This person as you can see has the APOE 33 genotype, which is considered to be more common and not necessarily a risk for Alzheimer’s or dementia, at least from a genetic standpoint, from the APOE standpoint.
The other thing that’s unique about my report is that there are external links to different research studies as well as websites that aggregate genetic information. If you want to go and do even deeper research, all of that data is provided. Here are the the back links to SNPedia to learn more about each of these snip variants.
The next section that was added is the autism related genetics section. This section is based upon a variety of different studies that found various associations to autism. Now, it doesn’t mean that these are predictive of autism necessarily, but the studies found that individuals that had the CAT haplotype, which consists of the DRD-1 snips, had a higher risk of having, in the autistic individuals had a higher risk of communication and social interaction problems, as you see here. The R is referenced as the actual research link where that study can be found.
That’s particularly relevant because this is the dopamine, these are the dopamine receptors, DRD-1 and DRD-2. Dopamine plays an important role in cognition and in memory and in communication and things like that. There are implications for, if you have an autistic child or if you are on the autism spectrum yourself, this section could provide potentially useful information, because when you think about dopamine receptors, you think about possible things that may be going on there. There are obviously different kinds of therapies that could be considered in that respect. There’s different amino acids like tyrosene, phenylalanine, L dopa, vitamin B6 that all can potentially support the dopamine pathway. But, just because you have the genetics doesn’t necessarily mean that that’s a definitive problem. A person can get by, a person can compensate for whatever genetic variations that they do have.
The next section is the brain health genetics section, and this basically assesses a variety of different variables that could be affecting cognitive function or brain function. We have both of the major MTHFR variants. We have some of the other variants like comt, COMT. As you see, this person is minus minus for these variants. GAD1, this is the gene. As you see, there are a few homozygous variants, so plus plus means homozygous, and you can see this person has some of these, that’s related to a gene known as glutamate decarboxylase which converts the excitatory neurotransmitter in the brain called glutamate into inhibitory calming neurotransmitter called GABA. Individuals with the GAD1 snips, they may have issues with anxiety because they may produce excessive glutamate. There may be some benefit to having more glutamate. Even though most people assume that glutamate is bad, which it certainly can be a problem, but person that has more glutamate may have a better memory, they may have better learning because glutamate plays an important role in learning and retention of important information.
The next section is the clotting section. Sometimes this can be very relevant if a person has blood clotting abnormalities. If they have a history of stroke or if there’s a history of stroke in the family, that can play out some significant or meaningful way. This information is provided to help shed light on the complex blood clotting system of the body. As you note, every one of the genes that is in the report has a description for what it is and a basic description of what it does, and links that take you to the outside of the site.
The next section is on the cytochrome P450 detoxification enzymes. This all has to do with a phase one metabolism, and phase one metabolism is also known as hydroxylation. Basically, what you need to know is that these genes are involved in taking some kind of a compound, whether it be a toxin or a drug or certain nutrients, and metabolizing it. Depending upon the different gene and the different snip, these variations can affect the rate of your metabolism. Most of this is happening in the liver cells.
This is the next section for detoxification. We added recently a variety of additional detoxification snips. The process of detoxification can also be called biotransformation. Sometimes people prefer that nomenclature because it’s a little bit more precise, as that you’re biotransforming some compound, and this is again, usually taking place in the liver. We recently added the UGT1A1 and 1A6 snips, and these snips are associated with a condition known as Gilberto syndrome. As you can see, this person does not have that, as it’s minus minus. But, this is one of these gene variations that can be significant and important. As we read the description of UGT1A1 and 1A6, we see that they’re involved in the conjugation of bilirubin, which is a blood marker that can actually be tracked.
What I’d like to do now is to actually show you an example of somebody’s bilirubin levels that also have this snip, and give you a little bit of a digression case study example of how this information can be useful. Okay, so we’re looking here at the UGT1A1 gene, and 1A1 and 1A6. These are referenced in the report, the Nutrigenomix report. These are significant genes that are found primarily in the liver, they’re expressed in the liver as phase two detoxification genes. They biotransform various molecules and, the process here of glucuronidation makes these molecules more water soluble so that they can be excreted. That’s how they’re detoxified.
The pathway of glucuronidation, which is what these genes code for, are integral for the conjugation of a compound known as bilirubin. Bilirubin is routinely tested in your basic blood chemistry, and it forms different conjugates. What this gene does is it conjugates bilirubin from its unconjugated form. But, genes are also integral in the formation of bile acids and various metabolites that get formed from this process. According to the literature, in the urine, glucoronides represent about 12 to 36% of the bile acids. Bile acids are really important for, they’re like the end product of detoxification in the liver. The gallbladder squirts out bile and then the bile is used to digest fats and fat soluble vitamins, like emulsifying and breaking them down. But they’re also, the bile contains different conjugated toxins and waste products.
Bilirubin is a waste product. There’s other toxins that get conjugated and glucuronidated. Hormones get glucuronidated, as we’ll find out. The UDP glucuronyl transferases, which is what UGT1A1 and 1A6 are, they detoxify toxic bile, cholestatic bile, like, stagnant bile in liver. Also, as I mentioned, conjugating bilirubin. They make different hormones, more water soluble. That includes estrogen, estradiol. At the thyroid hormones, T4 and T3 get glucuronidatad through these genes. A variety of different toxins including chemicals like benzene get conjugated through the UGT1A1 and 1A6.
What is Gilbert’s syndrome? Gilbert’s syndrome was first identified about 1901, so a long time ago. Individuals that have Gilbert’s syndrome, they have higher levels of unconjugated bilirubin because the gene defect, the UGT1A1 and 1A6 variants slow down significantly the process of conjugating bilirubin in the liver. Often, these individuals have consistently high levels of bilirubin in the blood. The medical literature doesn’t believe yet that there’s any problems associated with Gilbert’s other than the bilirubin. I’m going to present a little bit of evidence that refutes that contention, that dogma, because there’s actually a lot of other things that could be going wrong in people with Gilbert’s syndrome.
You can easily, as I mentioned, order the bilirubin levels on a blood test, and I find that again, very, very valuable. Because, ultimately what we want to track is gene expression. If the bilirubin levels come down because of some therapy you’d give, you know, that’s good because you can use a blood marker, the bilirubin blood test to see if it’s working. Just because you have the gene variant doesn’t give you enough data. It gives you clues as to what may not be working, but the blood is the trackable biochemistry, represents what you can use to really look at the things functionally.
Here’s the biochemistry of the bilirubin conjugation. The red blood cells which circulate, get broken down in the spleen, which is on the left side of your body, and then the spleen breaks down the red blood cells into constituent hemoglobin, heme, and then the HMOX gene breaks it into biliverdin, and then a the biliverdin forms unconjugated bilirubin. All that’s happening in the spleen. Then, the unconjugated bilirubin gets sent over to the liver where it gets glucuronidated by the UGT1A1, 1A4, and 1A6, and probably other ones. That forms the conjugated bilirubin, which then get deposited into the bile acids.
This process, particularly in the liver process is disrupted in people that have that gene variant for UGT1A1 and 1A6. This is an example of Gilbert’s, what it looks like genetically. It says that there is a strong, what’s called linkage disequilibrium. Basically, what that means is that when you see that one of the snips is plus plus, it’s almost a guarantee that they’re all homozygous, because they’re in this “linkage disequilibrium” with one another, so they’ll tend to follow the same pattern.
With Gilbert’s syndrome, it isn’t only about bilirubin, because a lot of things will also get glucuronidated. This is a short list of a number of different toxins and drugs, for example, that will get glucuronidated, and people with Gilbert’s syndrome, or another condition known as Crigler Najjar syndrome which is similar to Gilbert’s because it’s also a defect in the same glucuronidation genes. These people will have a very, very hard time metabolizing these drugs and these drugs can become very toxic. Hence, it’s useful to know if you have a UGT1A1 variance.
There’s other compounds that get glucuronidated besides bilirubin. The consensus that Gilbert’s syndrome is not a problem other than having high bilirubin just doesn’t make any sense. Here’s a study from 2008 that showed that the glucuronal transferases are responsible for conjugating and removing thyroid hormone from the blood. That’s very significant, and there isn’t really anyone that’s looking at this from the Gilbert’s perspective. We know that the gene is involved in conjugating other compounds, but the medical research hasn’t yet caught up to that fact.
The UGT1A1 and estradiol, this is another compound. Estrogen gets glucuronidated also. We may suspect to see that people with Gilbert’s syndrome could have higher levels of estrogen. They may have higher levels of thyroid hormone, and there’s been at least a few studies that show how estrodiol gets glucuronidated. The other thyroid hormone known as reverse T3, which is considered an inactive metabolite. At least, it’s considered that by most people. That is also glucuronidated.
There’s sort of this functional medicine discussion that’s ongoing about what does it mean to have a high reverse T3. Well, if you’ve got Gilbert’s syndrome, you might have your answer. It means that you’re not breaking it down. Clinically, I’ve observed that people, when they had Gilbert’s and their bilirubin goes up, it means that the enzyme in the liver or the UGT1A1 enzyme, its function is decreasing, and I often see higher levels of thyroid hormone and I may also see higher levels of reverse T3 with these clients as well.
This section is talking about how there is actually other genes that control the expression of UGT1A1, such as the PXR and the CAR. We know that there’s complex interactions between genes, and this highlights some of those. Here’s a case study example. This a female age 39, and as you see here on the left, here are her UGT1A1 and 1A6 snips. She’s homozygous. She has Gilbert’s, and there’s her total bilirubin of 2.5, that’s considerably elevated. She also has symptoms of constipation and bloating, anxiety that’s intermittent. It represents the probability that there’s something not happening with her conjugation in her liver and she may have a bile acid deficiency. Because, remember that a significant percentage of the glucoronides in the urine from bile acids are derived from glucuronidation. Here’s her a Dutch hormone test showing higher levels of estrogen. Again, because estradiol is glucuronidated, we would expect to see that the estrogen is higher, which we do.
This is another person with Gilbert’s. Notice the GI symptoms, the constipation, SIBO like bloating symptoms and some other GI symptoms. Homozygous for the variants there on the left. Then, her bilirubin is still high, a little bit lower than the last case, but it’s still elevated to 1.2. Again, the bilirubin is being used to track the gene expression of the UGT1A1 and 1A6 variants because these genes control the conjugation of bilirubin. Hence, it’s always good to see this, so I wanted to present this information to you to show you how we can track gene expression in some cases. This is the female, 34 with her, we also see that her estrogen is on the higher side of normal as well. Again, very interesting information, very relevant clinically, and gives you some information to go on.
