Functional Medicine Bitesized

A Beginner's Guide to DNA Health Testing | What Is It & What Are The Benefits of a DNA Health Test?

April 27, 2022 Pete Williams
Functional Medicine Bitesized
A Beginner's Guide to DNA Health Testing | What Is It & What Are The Benefits of a DNA Health Test?
Show Notes Transcript

The days of population advice on health for the individual is over. 

We now have the capacity to identify much of how we create health or sickness in an individual by getting a better understanding of  their genes and how these genes choose to express themselves based on the life we lead. 

Genetics expert Helen Gauche is interviewed by Pete. Helen provides a wonderful narrative of where we are currently with DNA Health testing. She explains how informative it is, what to look for in a test and in a company, and gives some great examples using Pete's genomic results.

Personalised medicine and personalised advice on health gets closer through understanding your genes and their expression.


Peter Williams:

Welcome, everyone, welcome to this new podcast of functional medicine bite sized. If you've been listening before, I think you pretty much know the drill by now we go around the world, and almost certainly going around the world today, because we are going to be talking to, I'd like to say probably continues to be one of my mentors, and that is Helen bouche, who's resides in South Africa Don't, don't you, Helen. So we're we are, we are literally halfway around around the world. So very much an international podcast at the moment. And, and as I say, Helen has been I've worked on and off with Helen, for quite a long time now. And I'm gonna let her introduce herself, but she really has been one of those key mentors for me in allowing me to better understand genetics, genomics and and better understand how they apply on an individual basis that helps us with with our patients. So Helen, thank you for continuing to take my calls, and answer my questions. And help me work out some of the ideas that I have in my head about how genes may be, ah, can express themselves over different pathways in different circumstances in different illnesses, you've been absolutely fantastic for that. And you continue to be so I really appreciate your time. And obviously, we're going to be talking about I think, I suppose the movement from population based advice and medicine and healthcare to more individualised advice on health and medicine. And I think this is where the role of genomics comes in. So can you just briefly give us your background on this? And why you're well certainly well I consider you a mentor, and very much an expert in this field.

Helen Gauche:

Thanks Pete. That's a big honour to hear that. And thanks for having me on the show, it's great to be able to share some of this knowledge with everyone. And I mean, my background, as you mentioned, I'm based in South Africa. So I'm enjoying the sun at the moment. But I'm a dietician, by training, and got into the field of personalised health care Nutrigenetics, over 10 years ago, now where I joined DNA life, which is a genetics testing company, there, and I started working through just learning learning the ropes and learning this really fascinating field of how we can improve our health, through understanding, you know, the key integral processes that govern our body. And by understanding how genetic variation plays a role in those processes. And so from there started looking really deeply into all of the research and and now heading up the the research and development at DNA Life for the nutrigenetic tests. So the the gene tests that you can see a gene environment interaction, where your what you eat, what you're exposed to, who you interact with, has an interaction with how your genes express, and how your gene variants influence how you, your biological processes react to the nutrients and the environment that you're exposed to, and thereby looking at how we can improve health?

Peter Williams:

Sure, I think that's a brilliant starting place. Can we sort of I think what we could do on here, isn't it, I think, I think it was just after 2000, where the human genome was mapped. And I think really everything has sprung off that hasn't it? Because not only was the technology, there was the information coming out with regards to genes. And that was really, I think that was quite revealing, wasn't it? Because what we actually found is humans don't have that many genes at all. I can remember a conversation where they've actually proven that a blade of grass has more genes than then a human does. And there's there's obviously a bit of nuance there because the microbiome has millions of genes. And I think that's where we learned that humans are both bacteria and human cells. But we've also learned that these genes can be quite flexible, Can't we even though we don't have many they they're not rigid. And would you can you also explain what gene variants are?

Helen Gauche:

Absolutely, So I mean, we starting from that, that human genome project. And even before that they kind of they were looking at gene variants, and I'll get into that term a little bit. But just starting off, you know, we have our genes that code for everything that is made in our body. So our genes are like our Blueprints. If you think of letters of the alphabet, that in different combinations give words, that we can then use to give instructions and to communicate with one another. That's how our genes are as well. But actually, as you say that it's I mean, it's hugely complicated. But when we think about the, our genes, we actually only have four letters compared to the many, many letters in the English alphabet. So the four letters in our genes, code for how code for words that then have certain, kind of make sentences. And those sentences are our strings of genes that give instructions for making proteins and making hormones and communicating with with cells in the body. And what happens is a gene variant is pretty much when there is a change in the spelling in those those letters. So those four letters, think of I mean, if we if we're using a word such as the word fit, and we exchange that I for an A, we suddenly have a different word being given, a different instruction. And that's similar for how these gene variants work is that when you have a change in one of those letters, how the eventual instruction to make a protein is going to happen is going to be slightly different. So when we talk about the gene variants that we report on, in the Nutrigenetics field, they're not they're not strong mutations. So it's not a completely different structure or completely a malfunctioning protein. But it's, it's a variant that leads to the same protein being made but slightly decreased or increased function of that protein or slightly different structure that would then lead to when we're thinking about where that protein is acting, and that overall biological pathway acting slightly differently. Or if it's a gene variant, in a gene encoding an enzyme that breaks down your caffeine, it's going to change how we break down our caffeine, do we break it down really quickly or slowly? So that's, that's kind of the concept of where these gene variants come through.

Peter Williams:

And can you can you just because I think this is a really an important point, isn't it? Is that what we're not doing here? When we're using these tests from a personalised medicine perspective? We're not looking at I mean, I tend to call them high penetrance genes, is that the right? There's a difference between genes that have these polymorphisms, they call them single nucleotide polymorphisms. And genes that may code for something like, like the BRCA, the BRCA genes that code for, you know, increased risk of breast cancer. So can you just go into that, because I don't want people to get confused who who don't understand the difference between strong gene influences and the sort of gene variants and polymorphisms in the single nucleotide polymorphisms.

Helen Gauche:

It's a very good point Pete. And if we think about it, actually taking the example of breast cancer, it's a very easy example and kind of concept to grasp where. And you know, if we think about the the number of cancers in the world, it's one of the highest causes of morbidity and mortality. And if we then think about cancers growing, you know, the increase in cancer incidence over the years, we can't just put that down to our genes, because our environment must play a role as well. So there's something kind of a clue in that. And so when we think about how, where do our genes fit into all of this, there are certain cancers that are highly hereditary. And that's what you you know, when we talk about the high penetrance, these highly hereditary cancers where if you've got a very strong family history of say, breast or ovarian cancer, and maybe your mom and your Aunt who had that cancer as well, generally at a slightly younger age, then you would maybe expect that your, your risk is also going to be higher and that and that could very well be true. For the reason that there are certain high penetrance mutations. So when we talk about high penetrance, the risk of the disease from that that mutation is much higher, when it's a low penetrance, we talk about many gene variants and combinations needing to interact with each other plus the environment to lead to the disease. So stepping back again, so the high penetrance, something like BRCA and a very good example is, I mean, taking Angelina Jolie as the example where her mom passed away of ovarian cancer. And that was because she carried a mutation, a high penetrance mutation in these BRCA genes, but also as individuals, and then say, and then Angelina actually got, she got tested as well. And she came out positive for these mutations. And so she took quite drastic action for decreasing her risk. So those mutations require quite drastic actions such as the double mastectomy or total hysterectomy. And but of all of say, the breast cancers that exist in the world currently, we can only attribute around 5% of all breast and ovarian cancers to these high penetrance mutations. The 95% are what we call multifactorial in nature, where it's gene on gene combination, many, many variants of genes. And we often look at polygenic risk scores when we look at that, and so many gene variants giving you an increased risk, together with what is happening in the environment. And that then, you know, starts to answer the question, or these clues or give us these further clues of there's an increase in breast cancer incidence, our genes haven't changed, they haven't changed that quickly over the last few 100 years. But our environment has changed significantly. So we always carry these variants, but what is it in our environment that is triggering poor expression or responsiveness for certain individuals to then go on to develop breast cancer?

Peter Williams:

Brilliant, thanks for that, because that gives us what's interesting about isn't it? I mean, I think I remember I mean, this is long time ago. So forgive me if this isn't correct what I'm going to say, but yeah, with the with the BRCA genes, the the, the risk is very high, isn't it? I mean, it's something like 80%, if I remember that you will go on to develop breast cancer. But yeah, there's still this argument that, isn't it? Well, what's happening with the other 20%? Why aren't they going on to develop it? And this is where again, I mean, again, I can remember being at a, I think it was an oestrogen metabolism lecture, and I think there was a specific researcher, there who was saying, who was investigating, well, why is it that some people don't go on to get it given that they have such a, you know, a high penetrance gene mutation? And that's where they were trying to look at the aspects of, well, what is it what maybe, by the way, they live their life that is maybe offsetting this? I mean, is there any more update on that?

Helen Gauche:

So they, so actually, it's, again, when you look at the BRCA mutations, and if one is considering going to get tested for BRCA mutations, because there's a strong family history, it's very important to go to a laboratory that has a very good database of it's almost the machine learning that that because of the the database that they've been able to acquire on information around the the history of those individuals, so there is that 20% where, there's it's a very strong mutation for brackets. So we know that BRCA is actually a tumour suppressor gene. And with the mutation it doesn't suppress tumour growth as as well. Okay, so that's actually how it kind of the the concept behind it. And obviously, with someone who then has a higher oestrogen load, a higher pollution exposure, a smoker, and those all then contribute, so there is still a part of that lifestyle factor involved. And, but it isn't when we're looking at the high penetrant penetrance mutations. um, you know, it's still quite, when considering how much risk is coming from, from the mutation itself, and your interventions for just saying, Well, if you improve your lifestyle, we can decrease the risk. It's not significant enough to be able to make that kind of statement yet,

Peter Williams:

and and to be to be clear, because I think what unfortunately, we're talking about here, aren't we we're talking about the data, you know, the, the the genomic tests that you know, someone who you know, maybe doesn't have a scientific or medical or health background, you know, can go online and go I mean, there seems to be DNA companies all over the place, now you can buy a test, you know, off the internet for a couple of 100 quid and then suddenly you're getting all this data. Because I think this is quite an important point for me, because what I want to do is I want to bring that into your company story, because I've had the privilege of working with you guys for over 10 years now on and off. And what what I've learned and been consistently using the genomic tests is that you've got to be pretty careful, haven't you? I think, careful what you're certainly what you say to patients. I think, if you're just doing the tests, and then giving someone a genetic blueprint for how their life should be led, could be problematic. And I know you guys are very strict on this. So can you basically give us maybe a little bit more of your company's history, but also some of the ways that you determine who can use your tests and who can't use your test? And then can you go into the why you choose the genes that you do that go into your tests, because I think this is an example of maybe it's, you know, it's actually maybe a good idea that if you want to start understanding your personalised genomic and genetic risk, or understanding that maybe you need to get someone who's got that experience, and quite a good background of understanding genomics, not just bringing a test off the internet, and then thinking that, you know, the answers that they give you are the ones that you need to follow for the rest of your life.

Helen Gauche:

Absolutely, and very good points made there. So I mean, starting off, they are there many genetic testing companies that have sprouted up over the last few years. Some of them being what we call direct to consumer. And that's where we as a company do differ quite strongly is that we go via healthcare practitioners, healthcare professionals. And and the reason for that is actually there's there's a lot of research that's been done into this area of, you know, what is the value of genetic testing, especially this this gene lifestyle kind of, thing for health. And, and really good and good universities doing research on this specific topic, and looking at the value that consumers gain from these tests, if they are done direct to consumer versus if actually, a healthcare professional is involved in the interpretation and counselling process. And they've seen that in terms of understanding the information, not being overwhelmed by the information, taking the information for what it really is, and then putting into practice the interventions in a kind of healthy, logical, systematic way, that has all been found to be much better when the healthcare professional is involved. And so that's how, you know, a lot of the time when these direct to consumer companies do one's genetic, or analyse one's one's genetics and report on gene results with a lot of advice. The problem with that is that the genes are only one component of an individual. And it's definitely it's a very important part, but it's definitely not everything, as you mentioned, the microbiome of the gut earlier, there's, there's just the individuals, you know, physical status, their culture, their dietary history, and their bloods that we haven't we don't have any information about. So there's, and then also what that individual is actually willing to change or not change, what supplements they're taking, what they're not taking, how much, you know, finances they have, all of that. So all of those things need to be taken into account when actually really developing a health intervention plan from the diet to the nutraceutical recommendations to the exercise recommendations. And that needs to be done in conjunction with the health care provider who then knows more about that person and has other expertise that they can put the full puzzle together. And so that's where us as DNA Life, we have chosen to work exclusively through healthcare professionals, who not only just you know, then use the tests, but actually get trained up in the testing and that's the other point with with a lot of the research that's done in this in this field is that the one part, side of the coin is saying healthcare professionals are, should be involved because they, they offer more value for the consumer. But the other part of the coin is actually saying that healthcare professionals, many of them feel inequipped, don't have the confidence and the knowledge to actually interpret the information. And so that's where there is this big knowledge gap. And that is what we strive to do is educate healthcare professionals to feel comfortable in this field, and to then go on to be able to interpret the nutri genetic tests in, in conjunction with what they are already doing in practice, so using it as a tool to improve the health of their clients,

Peter Williams:

that I again, I think, I mean, I've been using your genomics tests for way over 10 years now. And it's, I don't think you'll ever I think, in anything in medicine, or understanding or talking about nutrigenomics and gene variants, you just become better and better at understanding, the more you do, the more you use them. But again, I mean, I look at where I was over 10 years ago to where I am now. And it's just a whole different ballgame of being able to understand where that test or those panels of genomics that you've done fits into that patient's health. And if you like fits into their plan going forward, because I think there is this understanding that well if you understand your gene's, you're going to understand how your life plays out and what you can do, and it's absolutely not the case. So. So, you know, I think there are a lot of direct to consumer companies. And I think, unfortunately, in many ways, it gives good companies like yours as sort of you get grouped and get a slightly bad rap. What I would say about your company, I think this is really important is that there's a stringent, there's a stringent education process that goes into any test that you guys have developed. And that's really important, because what you're saying is listen, you know, this, this data used inappropriately, could have consequences. And so number one, you need to be highly educated by us to understand just the nuances of the test and where that test is applicable. And number two, we also have an Academy, which means that, you know, just because you've you've done the education, you're not going to be an expert in genomics, and you're definitely not going to be an expert in how to apply that to a patient that takes quite a while to get there. And as I say, I mean, you know, I'm probably what, nearly 15 years in now, and I'm pretty good at it. But I mean, I'm on the phone, I'm on the Zoom link to you all the time, because I'm sort of, well, what does this mean? And how does that link in? So I think what you're saying is that we're definitely moving from, but certainly with individuals from being able to give them population based advice to individualised healthcare advice. And the genomics are a part of that. But they're not the only part. Because, you know, I always say to people, the genomics testing is going to give us a better and more accurate indication of your book of life, what's been given to you, from your ancestors from the point of view of genes and point of view of gene variants. But then we've got to look at well, you know, let's have a look at your lifestyle and maybe do some blood tests or some urine metabolite tests that actually see, well, how good a shape are you currently, as far as health, based on how you feel and what the test results are telling us? And let's assume that there's maybe some markers that are out of shape? Is that out of shape just because that's a picture of your life at that current time? Or is that something where, maybe we can start having a conversation about, this is unusual, you've got very high needs, I'll give you an example. Very high needs for folic acid and B 12 on your test. And you can link back to having a conversation of the family history and then you can think about, okay, maybe there are some problems around methylation pathways and gene variants from that side. So for me, I, hence the reason why I continue to work with you guys is that I think you've really thought about that. And you're not ones that have just thought, well, let's just sell a test and we'll sell as many as we can and make a huge profit. There is a there's a sort of, there's a key aspect to be able to be giving genomic testing and education in the right way to the right people in the right structure. And I think you do that brilliantly. So well done.

Helen Gauche:

Thank you, we keep trying.

Peter Williams:

Well, you know, you do try and as you say, you know, I think you're doing that really, really well. Let's, can we can we sort of talk about, I'll just give us some just examples of, of, you know, imagine we did a DNA test and we looked at a certain gene, and you can pick whichever you want Helen. And we'll talk about how, what a gene variant is because in many ways, I always say to people, you know, sometimes those genes, depending on the variant, and the way you live your lifestyle, which is the important thing, either codes for health, or you can choose a lifestyle that codes for disease. So can you sort of give us a bit more of an understanding of that?

Helen Gauche:

Okay, so asking me to choose one. And I think we go, I'm going to choose a sort of one or two of the genes that are actually involved in vitamin D metabolism. And the reason for that is I think, one, you know, Vitamin D has been strongly spoken about in the news recently and spoken about in terms of immunity and how big a role it plays in immunity. And I'm also going to choose it because hopefully, everyone's kind of familiar with the concept of vitamin D. So we can discuss that part. So it's quite an it's one of the easier metabolism genes to understand, the activation is very complicated, but the metabolism is slightly easier than getting into say something like methylation, straightaway,

Peter Williams:

because this is a this is a brilliant story about my gene results. And also, what I found incredible given on the first summer of lockdown, I mean, we really, you know, basically work what there wasn't any work, it was really sunny, I basically spent most of the summer in the garden, getting brown as a button. But then later found at the end of the summer, when I usually get everyone to do their serum tests and vitamin D, I was only around about 86. And I was like, What the hell's going on here? How can that be the case. And, you know, it later found out that I had a whole host of these gene variants with regards to vitamin D. So and that really got me to get this deeper dive and understanding of just the sort of mechanistic way that vitamin D tries to get to the to the target cell. And it's pretty damn complicated.

Helen Gauche:

And, I mean, yours actually sounds better than a lot of people's do, even even with your variants, but I'm sure the lifestyle was good, at least to make up for it. So and So as an example. So if you take a genetic test, and in the one of the tests, you will get a host of genetic variants that are reported and they're reported based on, we choose them based on their, the level of evidence that is available to us. What if there's something you can do about it? So we need to have some kind of action that can be taken, it's not just oh, well, that's, that's nice to know, or not not nice to know, when that same kind of action on it.

Peter Williams:

I know, I'm butting in here, because this is another standout point with regards to your company. And many of us as far as I see it, so can you just just dig into this a little bit more, because this is a really, really important aspect, because you can get a, you can get a DNA result that has done 1000 of your genes, and it looks all impressive. But do you want to do you want to explain? Yeah,

Helen Gauche:

Sure, okay, so there are tests or they are reports that offer 1000s of genes and and then often, you know, practitioners or consumers would come to us and say, Well, you know, this, this report has so many genes, why are you not putting in more, or have you considered adding this one in or that one in? And it's, of course, we'd look at it, and we and then we, you know, if we're missing something, we definitely review the snips. But what we and we're constantly doing that because the research is growing so quickly. But something that we want to really stick to when looking at the what we call the the gene variants selection criteria when we when we report on genes and their variants is we want those genes to play or to see them playing an important role in biological pathways. So what I'm why that's important is that if we're able to target that gene expression to maybe subdue the expression or increase the expression, it has a major downstream effect. So it's quite like, they're punchy genes they've got they've got a lot of influence over our body. And so when we're looking at variants in those genes, it's nice because there's just, you know, you can get quite a strong outcome for maybe not a huge amount of work in terms of intervention. So that's, that's something we start looking at just in terms of when we start looking at pathways. And the next thing is the variant on those genes needs to have some kind of it needs to be a functional change, we need to know that when you have that variant on that gene, it's actually going to change how that enzyme or that protein expresses whether it be a higher or lower expression. So it's pretty much if you think about a factory and the gene being made, are we going to have more of that gene being made or less of it being made or when it's made because of the variant is it going to have a different structure and thereby cause a change in the pathway or a change in a health outcome. And so with that, we also from there, we want to be able to see from the research has it been associated with a specific health outcome or a specific biomarker such as vitamin D status. And then we want to be able to say, okay, based on that, can we do something about it. So taking the vitamin D genes as an example, there is something we can do about it, we know that supplementation can increase the vitamin D status if inadequate and the right amounts and the type of vitamin D taken, and you're able to, and with these variants, there is the a gene environment interaction. So it's not just saying it's a gene, phenotype or a gene interaction with what, with cholesterol, but there's nothing we can do about it, or with vitamin D status, but there's nothing we can do about it, there's something that we can put into place to change that outcome. And then lastly, we want to be able to measure that outcome. So measure, so looking at the genetic variation, and be able to see, okay, well, your vitamin D status was below par over here but with supplementation, we can then measure that vitamin D again, so there's a biochemical test that we can measure to assess a change and the outcome. And so that's what, it's a lot of research and a strict criteria that needs to be met. And then obviously, the evidence needs to be there. So we look at the research and we see has this been studied in different populations? Has the outcome been replicated? The same outcome been replicated enough to be able to then say, okay, there's something to this specific gene variant, so we can include it and report on it with confidence. And so that's, that's kind of the criteria that we go to before we, you get your report.

Peter Williams:

And the key on that, isn't it is that the reality is, is that, number one, you're only picking the genes that have high quality research behind them? I think that's number one, I think number two is that you've got to be able to take that gene variant result, and be able to act do something actionable about it with regards to something along the lifestyle. And also what you're doing is that is, is when you generate your reports, you're giving the practitioner and the patient, a menu, if you like to say, look, here's the gene variant, here's potentially what you can do in lifestyle, either for good or bad i.e. if you've got a crappy lifestyle, it's going to accelerate problems here. But if you change your lifestyle, it's going to decelerate problems. And if we wanted to sort of see how that's going on a day to day basis, here's the tests that we would look at to measure how well you're doing. And I say with vitamin D, you'd be looking at the you know, the the blood levels of vitamin D. Can you just go through because I because I absolutely find your vitamin D panel fascinating, because can you just tell the story of vitamin D synthesis, because I think this is super cool. And, and for me, it's been a massive eye opener, not just for me, but for my patients. Because I think what it's doing the story of what it's worth, you know, inactive vitamin D be made in the skin, it's got to be transported to the liver, the liver has got to change it and it's going to be transported again. And then it's got to get to the cell. And all those gene variants influence what your vitamin D levels are going to be. But the beauty of this is that it's taken population based data. And there's a big argument isn't there in the literature about how much vitamin D you should take. And we know that population based data is always done on a Gaussian curve. So you see that sort of bell shape. And most of my patients are around certainly me as an example isn't complete outlier to that bell curve. So I don't fit into that research that population based research at all. And as a consequence of that, I've got to take significantly more vitamin D levels to try and get at an appropriate level. And again, if we were talking about COVID, the minimum level that seems to show protection for COVID 125 nanomols, and I was miles out of that and that was even with, you know, a Summer of pretty, pretty full on sunshine. So could you just talk about that, that sort of vitamin D metabolism and just some of the genes that you're measuring, because for me, this is just a super cool story.

Helen Gauche:

Absolutely. So I'm gonna do it quite simply. But really, what happens is one of the best places that we can have our vitamin D, or we can have, it's known as the sunshine vitamin. And the reason for that is we get our vitamin D, pretty much from our sun from the sun, it gets activated and then synthesised in the skin. And, and there are different enzymes that are involved in doing that. And so when we've got our vitamin D molecule that has been made, it then needs to be transported to the next organ, where another conversion will occur to make it more active, so every time it kind of gets, it gets synthesised, but at every kind of point in the conveyor belt line, we have a more active vitamin D being made, until it gets to the liver, where eventually it is completely active, it's the right form that we want to then be able to be transported to our our cells. So it goes by this kind of transporter, we can think of it as like a little cart, that's transporting the Vitamin D to the next point, and at the next point, it goes through another, so it gets to the liver where it gets activated by another enzyme, and then it gets transported again, by the same little cart to to our cells that need it. And then on our cells, there's kind of like a secret key that only vitamin D knows, and then that key needs to be opened or that key needs to be used to open the door to let that vitamin D into the cell and into the nucleus to actually then go on to do its function. So it has many, many functions. One has a very important role in in bone health. Other functions include regulating inflammation and immunity, for example, so so when we have a genetic variant at any of these points, and whether it be in the activation, from in our skin, in the genes in the enzymes that are working there, or the genes that are encoding this, this little cart, this transporter, so say for example, you have a variant on the gene that encodes or makes the transporter, if that variant in that gene is saying, you're going to make the transporter, but the transporter is going to work really slowly, or can't hold as much vitamin D at any one point in time, then the ability to transport vitamin D to the next point on the conveyor belt or to the liver is going to be slower as well. So you've already got this, these kinds of weaknesses that might be occurring at different steps of the pathway. When then, if you get to the liver and the genes encoding the enzymes that are involved in activating the vitamin D to its active form to its useful form, that the body can actually recognise and really make use of, if that activation process is not working as well as we would like because again, the variant on the gene is encoding for the enzyme that activates it, but it's just not doing as good a job which it's working really slowly, then the the amount of active D in our system at any one point in time is also going to be lower, and then that transport comes in again. So again, then if the transport isn't working as well, we're going to have issues getting that active vitamin D to the cells and to the nucleus of the cells. And then from there, we want to make sure that that key is working really well that vitamin D key is working really well. And that's where we speak about, I'm talking about the key for the receptors to actually say okay, I've got this active D and it needs to attach to the receptor, but it will only attach nicely to that receptor. If the the receptors are very sensitive to this active D that has been transported in sufficient amounts. And if we then have this key not working so nicely or this receptor not working so nicely again because of a variant that makes it less sensitive to kind of recognising the vitamin D coming in. That's another point where then the activation of that vitamin D or that that reception of that vitamin D to then go on to perform its duties in bone health in regulating inflammation in calming the immune system or just really balancing the immune system. All of those factors then are also put at risk. So there, it's a complicated kind of step by step process where some genes, you will see come up more than once because say, for example, the transporter, it's the same transporter working in different points. But if you've got a variant on that transporter, it's going to have a major issue on vitamin D metabolism. So in our test, we, we look at variants that have been found on the transporter gene, on the activator enzyme to make vitamin D active. And then we also look at, we look at the the receptors of vitamin D, and looking at variance over there. And if you have variance in one of those areas, it'll lead to a weakness in this whole pathway. But if obviously, you can have a compounding effect, where if it's a variant in one gene and a variant in another gene plus a variant in another gene, we could almost call that a polygenic risk increasing. So 'poly' more than one 'genic' - your genetics, so more than one gene risk, around vitamin D contributing towards your vitamin D status. And there are really interesting research articles looking at responsiveness to vitamin D supplementation with regards to these genetic variations plus other factors as well that play a role. But there's definitely evidence showing that when you have variants in these genes, your responsiveness to supplementation, to exposure to vitamin D from the sun, is going to be lower so that you you're not going to get that expected incremental increase in supplementation that you might expect, if you have a variant in these genes. And then when, like yourself, Pete, you're going to do the blood tests to check for vitamin D, you can see, okay, well, I have the variants, the risk variants coming up. And now I can see, based on my Bloods, there's definitely a correlation coming through there so now what must I do about it, I have to ensure that my my vitamin D intake throughout the year, on a daily basis for the rest of my life, is going to be adequate based on my genes.

Peter Williams:

So let me just say to everyone who's listening to that is about the most up to date, explanation of where we are with vitamin D physiology on a personalised basis that you that you're going to hear. And I think that is one of the beautiful things that I think if you, if you have someone who understands genomics and understands the application of gene tests, can explain to you in that way that you've just done Helen, the importance not only and I mean, I look at this, and everything that you've explained, is part of some of the quizzical patterns that I've seen with vitamin D levels with many of my patients over the years. And from that we started doing the patients that well, you know, you know, the same line is that, you know, you ask the questions before, because obviously, you don't want to lead them straight into testing, how much sunshine do you think get through the year, "I get loads, I'm on holiday all the time". Okay, great, then we should expect that these are going to be great, and they come back, and they're really not great at all. And you're like, really? Okay, and then of course, you as you've just explained, based on your tests that you're doing, it suddenly is all there open. And I think the key for this is that this is where I believe as you say, as we move to personalised medicine and personalised health care, the influence on something just as simple as Vitamin D, we know from a physiological perspective, that there's a receptor site for vitamin D on every single cell that resides in the body. So it's pretty crucial. And and really for for pounds, or a few rands, you're getting this sort of individualised data that as you say, and I'm saying to many my patients now based on the data and based on how we follow them with blood tests over time, look, we've traced your blood tests over time here, they've never looked great for vitamin D. And we've supplemented you on a moderate dose. It's never really picked it up. And now we've got the genome data that maybe isn't given as the absolute 100% answer. But we're bringing you close to the fact that I may have to prescribe vitamin D supplementation throughout the year and we may have to test you twice a year to make sure that your blood levels are adequate because of this sort of overwhelming influence, that something as simple as Vitamin D has on health. And I think that is the big takeaway for me for over the last 10/15 years have been able to transition and translate this genomic information into the sort of, into an individualised health programme if you like going forward. And I think that's the beauty of it. That's the power of it, it gives you but to do that, as you say, you've got to have the context of your patient, you've got to understand the background. And you know, if you're lucky enough, you've also got to be able to understand what has former testing showed you. And has there been any patterns that that consistently show up because those patterns may be associated with gene variants that are always going to be there. And again, another example of this, we see this with alterations in in in red blood cells, we see this with high levels of homocysteine, it's a blood protein that you test that increases your risk for cardiovascular disease, but also dementia. And you start thinking on that. Okay, I've seen this quite a bit. And therefore, it's probably a good idea that given the consistency of levels that we're seeing that maybe this is an idea that we should go and have a look at those genomics. And, you know, the key for me on this is that the genomics, I think for what you get gives such an incredible dataset where and genomics is cheap these days, isn't it? I mean, some of your tests are for what they are, I mean, I just they're incredibly cheap, I believe, anyway. And it's a no brainer to me that, that you wouldn't do it. But of course, the key is, is that you've got to have someone well trained to be able to sort of give you the fuller picture and be able to translate all these messages into simple stories about what you've got to do on a daily basis. Just I'm curious about, I'm curious about the vitamin D, because as you say, mine's a horror show. I mean, and we talked about having these areas where it's not just about one gene influencing, you may have a situation where it's it, we call it compounded, don't worry that it's the word that mean you like to use compounded or amplified. And so right across everything we've just talked about, I seem to have really quite high level gene alterations. And I think about that, Helen, I think, all right, okay, I'm a I'm a Caucasian man living in a Northern climate. And we know that, you know, the reason why we have dark skin and we have white skin is because it's a gene mutation over millennia, that is, you know, your skin becomes lighter, the further north you get, because there's less sun and suns pretty much crucial to life. So given that you've got someone with so many gene variants like me, who I wouldn't say, I mean, I tan quite well, but I wouldn't say I've a Mediterranean skin, is that suggestive of sort of a strong ancestral background of maybe that, you know, I'm, I suppose we could go back and say that I'm probably African is at the end of the day, is there any relationship?

Helen Gauche:

Sure, you know, that's, that is an area that I am not comfortable in is the population genetics, but, you know, it's, they do a lot of research around, actually, they have done a lot of research around the vitamin D metabolism genes, and then obviously, looking at ancestry 1000s and 1000s, origin of ancestry, because, you know, we know that there's there's a strong relationship between skin colour and, and these genetic variants, because obviously, if you had a darker skin, you didn't need that much sun because you were getting it. So there's definitely that aspect that goes into it. But when we speak population genetics, they, they have very clever algorithms, it's a different field altogether. And that looks at 1000s of genetic variants, and some of these included, but I don't think he'd be able to comment on and give the right answer.

Peter Williams:

But I think, what I'm trying to think of here is that theoretically, you know, somewhere along the line, you don't need this one. You don't need this one. And you don't need that one, which makes me think, well, maybe, you know, hundreds of 1000s years ago, at all my sort of ancestors were definitely hanging out where the sun shone.

Helen Gauche:

Yeah. And they were and they were okay with it. And that's a very good point to make is that there's no such thing as like, you know, for these genetic, these low penetrance variations that wasn't good or bad. It's based on the environment that you're exposed to. And, and that's the thing is that, you know, some some gene variants they develop for a reason. So if you were in an environment that had a high pathogen, you were exposed to lots of pathogens and, and kind of, yeah, lots of nasty infections, from the environment all the time, then you wanted to have an immune system that was on super high alert to defend yourself against that. So maybe your inflammatory and oxidative stress response was highly alert and kind of over the top, but it protected you from those pathogens. So your immune system was kind of sensitive to that. But then you put someone like that in an environment that doesn't have those pathogen exposures, but all of a sudden has a modern Western lifestyle of lots of saturated fats and refined carbohydrates and inadequate nutrients. And then all of a sudden, it's going to drive a chronic inflammatory oxidative stress profile over many years, which then has different chronic disease outcome risks.

Peter Williams:

Sounds like you're talking about me exactly again, I mean, you know what my inflammatory genes look like, they're a horror show aren't they? So this is really interesting, isn't it? Because when we look at me, we know that I've got a terrible pro inflammatory pathway, and genes that sorry, not pathway, but genetic profile, that really and you know, an APoE3/E4, so I am really set up for almost like, you know, I would have done pretty well, you know, millions of years ago, because I was more set up for, if you like the trauma of what life was like, Yeah, and I'm not set up for living this lifestyle, and probably, I'm certainly not properly set up to be living to 100 unfortunately, and I know, we can't, we're making assumptions on that. But, you know, I think this is the beauty of being able to get a rich data set on the genomics and the genomic variation, and be able to make some really good assumptions based on very solid science, about how you sort of build a programme for you, you know, particularly as you age. And we've had incredible success with with our patients on this, but I wouldn't say it's not just down to a brilliant gene company, it's also down to the way you've, I think, importantly, the way your tests have been written, I believe, are really quite, very patient friendly. Because again, I've many patients that come in who have done, they've done the genomics on their own, and they just get a raw result. And when they bring it in, I go like that mate, I'll just I'll be clear, I've got no idea what this means. There's no application for me to utilise this in clinical practice. And so I'm not going to be going looking through this, if you want to do some genomics, we need to go through this way. And so that I can understand more clearly, because it's far, far too complex, to be able to give you personalised data based on just raw data that's been spewed out from from somewhere else. Helen, I'm going to be having I mean, this is just we could go on for days on this, because it's super, super exciting. And what it does is that, you know, there is no doubt that healthcare has been changing very rapidly over the last 20 years, there is no doubt that healthcare is moving from population based to individual care based, and genomics are one of the key ways that we can move patients to be making individualised decision making from that. And I'm going to be interviewing you again and again, and again, because I know you've already agreed, and then you probably don't remember, bit I'm gonna remind you, I want to do a podcast on my on my I think mine and possibly your favourite gene variant, and that's the APoE gene variant, which is, you know, is the gene that is predominantly being called the Alzheimer's gene. And I'm going to get you on pretty soon on that one to have a chat about it. Because, again, I have one of the gene variants that increases my risk of Alzheimer's disease, but also it's, even though we're looking at low penetration genes, this is quite a player, isn't it? I mean, it does have quite a strong link to, to, Alzheimer's. If you are going to summarise because what I wanted today is almost like I wanted to do you know, here's the introduction to understanding genomics, here's some of the pitfalls that you know, are from you just getting a direct to consumer one off the internet and I think we've done that. If you were going to summarise and give advice to people in the street knowing quite well that I'm going to have our in house resident expert Helen coming on and talking about genes. And then then we can dig into almost like maybe sort of biological areas like inflammation and again and discuss sort of just tell the story about you know what that means and you know, the APOE gene, what what would what would be the information that you would give someone who might be listening who is interested in having their genes looked at because they want to build a more individualised healthcare programme as you go forward. What would be your summary for this?

Helen Gauche:

I mean, I would say, it's definitely something that if you are interested in a personalised approach in seeking out to not just live long, but live well, and to try and solve kind of mysterious health issues, this is going to provide great insights for you to do so. And I would recommend getting in touch with a functional health professional who is very comfortable in the space, who has done genetics training, Nutrigenetics training, so they are comfortable with the interpretation of this kind of data, and you should be able to ask the, your health care practitioner, then, you know, which tests do they work with? And why do they work with them. And I think they should be able to give you those answers based on what we've discussed today. And then from there, it's working with someone, obviously, that you're very comfortable with, and being able to discuss with them your full history to then use this information to put into kind of your specific, your unique puzzle to improve your health. And then just the last thing on it is that it's, you know, I I'm very much an advocate for this field, for this science. But I'm also the first to say that it's not everything, we don't know everything, but we don't know everything about anything in the health yet. And it's an it's a great stepping stone to I think put one in the right direction for understanding where can you get your kind of your bang for your buck in terms of putting in interventions that are going to get you the best outcomes. And lastly, it's you know, it's great information, but it's not a magic bullet, and the interventions still need to be put into place. And that's where your motivation comes into play, and really needs to, you need to kind of come to the party to be that that change for your genetics,

Peter Williams:

I think really well summarised, and well said. Helen, thank you so much for today. It's going to be one of many. So I'm going to be reminding you on that. I really appreciate your expertise and your expertise over all these years in helping me trying to not only get better at learning genomics, but help me sort of think about a lot of the stuff that I think about with patients. I think that's a brilliant introduction lecture and I totally can't wait to have you on again on my favourite gene APOE. So that's the next one coming up.

Helen Gauche:

Thanks Pete, it's a real privilege. Thank you