The Peter Attia Drive - #67 - AMA #8: DNA tests, longevity genes, metformin, fasting markers, salt, inflammation, and more

Episode Date: August 19, 2019

In this “Ask Me Anything” (AMA) episode, Peter answers a wide range of questions from subscribers. Bob Kaplan, Peter’s head of research, asks the questions. If you’re not a subscriber and listening on a podcast player, you’ll only be able to hear a preview of the AMA. If you’re a subscriber, you can now listen to this full episode on your private RSS feed. You can also watch (or listen) to this full episode on our website at the AMA #8 show notes page. Questions continue to be pulled from the AMA section on the website, and any subscriber is welcome to submit questions for future AMAs. We discuss: Do DNA kits provide actionable info for cancer, CVD, diabetes, Alzheimer’s, nutrition, or exercise? [1:45]; What genes increase longevity? And do those genes show up on genetic tests like 23andMe? [12:00]; Who are some people that Peter would like to have as guests on The Drive? [15:00]; Inflammation: Is CRP a useful marker? What can one do to reduce it? And what other inflammatory markers can I look at to gauge health? [18:30]; What lipid test does Peter now use on his patients? What are the three best cardiovascular laboratories? [28:00]; Metformin for longevity: What considerations should one think about before doing taking metformin for longevity purposes? [32:30]; What is Peter’s take on salt and its role in things like high blood pressure and stomach cancer? [40:00]; What markers does Peter find most interesting (and surprising) during his quarterly fasts? [47:30]; and More. Learn more: https://peterattiamd.com/ Show notes page for this episode:http://peterattiamd.com/ama08 Subscribe to receive exclusive subscriber-only content: https://peterattiamd.com/subscribe/ Sign up to receive Peter's email newsletter: https://peterattiamd.com/newsletter/ Connect with Peter on Facebook | Twitter | Instagram.

Hey everyone, welcome to the Peter Atia Drive. I'm your host, Peter Atia. The drive is a result of my hunger for optimizing performance, health, longevity, critical thinking, along with a few other obsessions along the way. I've spent the last several years working with some of the most successful top performing individuals in the world, and this podcast is my attempt to synthesize what I've learned along the way to help you live a higher quality, more fulfilling life. If you enjoy this podcast, you can find more information on today's episode and other topics at peteratia-md.com.

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by signing up from monthly subscription. Welcome to AMA number eight, featuring once again my head analyst, Bob Kaplan. In this episode, we talk about my thoughts on DNA and genetic kits, genes that can drive longevity, top guests that I'm hoping to have on future episodes of the drive, inflammation and inflammatory markers, NMR-Lipoprofile versus other tests for advanced cardiac measurements in addition to a conversation around the recently emerging

use of electrophoresis. We'll talk about taking metformin for longevity, as well as a little side conversation around burberine. We talk about what drugs I think are the most exciting drugs on the planet today. We have a little conversation around salt. And we talk about markers and metrics that surprised me during my most recent nothing burger. As a reminder, AMAs are for subscribers only. If you're not a subscriber, you'll only be able to hear a preview of the AMA here. If you are a subscriber, and hearing this, it means you have yet to download our members only podcast feed. With this members only feed, you'll be able to subscribe to the drive in your podcast player to get every episode of the drive without the subscriber call out, plus full episodes of the AMA podcast directly, along with other exclusive content.

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So without further delay, please enjoy AMA number eight. Hi, and hello podcasters, Bob Cafflin here. Peteratia over there. Let's light this candle. Sorry for slurping the mic. Excuse me. He's a little hot. Here we go.

Our DNA kits useful in providing actionable info and any thoughts and information on using genetic testing to guide nutrition and exercise. I assume they're talking about like 23 and me, that type of SNP testing. I mean, I think we need to put this in a broader context, which is exactly 20 years ago, we were on the cusp of, and by we, I don't mean me, I specifically exclude myself from being a part of that.

You mean Watson and, yeah. Exactly, yeah, exactly. We were on the cusp of what was hailed as perhaps the biggest revolution in all of medicine. It's one thing to certainly understand the structure of what DNA meant and how to understand the coding language and how DNA becomes a template to make RNA is the template to make protein. But 20 years ago, sitting there on the cusp of actually decoding the human genome, and we now know that there are, it depends. I mean, I used to typically nominally say 20, actually decoding the human genome. And we now know that there are, it depends. I mean, I used to typically nominally say 20,000 genes in the human genome.

I think some would actually revise that upward and say maybe even closer to 30 now, but relatively finite number of genes. And it turns out that hasn't panned out. This notion that knowing the genome was going to change everything, it hasn't panned out. It hasn't panned out for several reasons. So first of all, most things that we concern ourselves with are either wildly polygenic or the only way you get the thing, either good or bad, is when the environment for lack of a better word turns on the gene.

And so, if we talk for a moment about the pathology side of things and use cancer as an example, this seemed to be the most interesting place where we would think that the genetic revolution would help, and that by knowing your genes, you might know your susceptibility to a type of cancer. So, I think the first thing we want to talk about here is the difference between somatic mutations and germline mutations. So the germline is the gene that you inherit.

So when you do a test like a 23 in me, I think for the purpose of not getting too far in the weeds on this, this is actually worth a dedicated podcast. Maybe we can make a note of that and just do a dedicated podcast on genetic testing because it is such an important topic. I'm not going to get into the difference between what a 23 and me is doing versus what a whole genome sequence is doing as far as the accuracy of it. So notwithstanding the huge inaccuracies that show up when you do these

short-kid SNP tests, what you're doing is looking at the template you inherited, hence germline. Now, there are some cancers that are driven by germline mutations. In other words, there are a subset of cancers where just knowing you inherited a certain gene dramatically increases your risk of that cancer. So the BRCA mutation would be an example of that. Lynch syndrome, which is an acquired genetic syndrome, would be an example of that. Where all of a sudden, you have one of these mutations

and the probability that you're going to get cancer is very high. In the case of Lynch syndrome, it's virtually guaranteed. You're going to get high. In the case of Lynch syndrome, it's virtually guaranteed. You're going to get cancer in the case of Braka. It's not quite as high, but depending on which variant of it, it can be still quite high. Probably approach is 80% with at least one variant. Would knowing that information be helpful?

Oh my God. Of course, it would be helpful. As a general rule, unless you are adopted, you generally know that without a genetic test. That's how penetrant these things tend to be. So in other words, it's very unlikely that you show up in your in your 30s or your 20s and you know your ancestry, so you know who your parents are

and you know who your grandparents are and aunts and uncles, you're gonna get a surprise on a genetic test by showing up with one of those centers. So the first thing I put on the back of my mind is patients who are adopted probably benefit from this. And I have a friend who was adopted and who got Lynch syndrome. And that was a real surprise to all of us because why was a guy in his early 40s getting colon cancer? And especially the way he got colon cancer was very atypical in terms of the actual clinical presentation of the disease. And of course, because he was adopted, we don't know that clearly one of his parents also

would have gone through this. But the probability that you are listening to this and that you have this, it's very love. This is a kind of a long-winded way of saying that probably north of 95% of cancers are not germline mutations. They are somatic mutations. They are mutations that are acquired after you've received all of your genetic material. And I think we've known that for quite some time.

We didn't need sort of the coding of the human genome to figure that out. But the problem is the current type of genetic tests that I think this question is asking about don't measure those mutations. You can't find those mutations in the DNA of the base cell. You have to look for those cells like a needle in a haystack. You're looking for those cells usually in the blood. And the good news is there are companies and technologies that are looking at these things. This belongs into a subheading of things called liquid biopsies, where you could do a blood

test, and in theory you could find that needle in a haystack. You could find that cancer cell. You could say, wow, this is a colon cell, and it has an acquired mutation, and that mutation is giving it the capability to escape the colon and take up residence somewhere else. So I think from the standpoint of cancer, I don't think there's a lot of value. From the standpoint of cardiovascular disease, I would also say very little value. The most important genetic test that you would look at from a heart disease standpoint would be LP little A, which we've spoken about at length. So if you have the LPA gene, which, honestly, somewhere between about 8 and 12 percent of the population does, maybe even higher,

that's important to know. But guess what? You don't need genetic test to do that. You can just which, honestly, somewhere between about 8 and 12% of the population does, maybe even higher. That's important to know, but guess what? You don't need genetic tests to do that. You can just measure the phenotype, meaning you don't need to know if you have the LPA gene, you can actually measure LPA little A. It's even easier to measure. So again, that sort of alleviates somewhat the need of knowing that. Now, whenever someone gets one of these tests, it tends to spit out a lot of information, like you're at increased risk of heart disease, you're at increased risk of diabetes.

I think this is an area where I probably differ from a lot of the current crop of people who love precision medicine. And I don't find that information very helpful. I think that if you go deep enough on the phenotypic side, you will get that information and you will get it in an even better way, and you will have a metric with which to track as you try to reverse the process. So, taking diabetes, for an example, does it help me to know that someone

has a genetic predisposition to type two diabetes? Not nearly as much as it helps me to know while they are still non-diabetic that they have hyperinsulinemia. And even if they don't have it while fasting, to know that they have post-prandial hyperinsulinemia, it's very important. To look at other subtle markers of insulin resistance, the elevation of ferritin, some of the other things that we see, other patterns of glucose disposal. These things matter a lot more, frankly, just wearing a CGM and knowing

over the course of months how your glycemic responses. That is orders of magnitude more insightful and perhaps more importantly more actionable. So I think the one place where I do think that the genetic information can be somewhat helpful is with Alzheimer's disease. I do think that knowing your ApoE status is quite an empowering thing. I think truthfully, I don't think it should change that much of what we do. In other words, even if you have an apoe3 or an apoe2, it should be a much lower risk gene.

I wouldn't let that information in any way, shape, or form, detract me from taking an all hands-on deck approach to avoiding dementia. As Richard Isaacson said, when we had him on the podcast, if you have a brain, you're at risk of Alzheimer's disease. And so, even though 25% of the population has APOE4 positive gene, meaning they're either one or two copies of APOE, and most of those 25% are single copy, they make up about two thirds of the case of Alzheimer's diseases.

But of course, that means 75% of people who don't have any E4 still make up a third of the cases. So in that sense, E4 is helpful if you need a little extra motivation to work harder. Again, it might be a little helpful if you're thinking about it through the lens of your kids. Should your kids play contact sports, we talked about this before where this susceptibility to head trauma could go up with an ApoE4. So maybe that causes to think, we'll play tennis instead of soccer. One of the questions was about nutrition, I think, and exercise. And I got to tell you, I am still not convinced that we can extract much value vis-a-vis what we should be eating or how we should be tailoring our exercise from the current genetics. Now, there are probably some tests that are emerging that could be kind of interesting.

There are probably certain genes in the P. par family, for example, that might speak to our ability to metabolize fat, that might speak to whether or not we will do better or do worse on a certain type of diet. But I would counter that by saying, you can empirically determine that so easily that I'm not sure it's adding value. And even if you saw that you had a genetic predisposition to one diet or another, it still doesn't mean that that's going to work. You still have to go through the empirical step.

So I think there's a long-winded way of saying, I'm just not over the moon excited about using sort of the current crop of genetic tests. Although we do it, and virtually every one of our patients comes in the door with a genetic test, usually it's sort of one of these cheap, kind of easy SNP tests. Probably 10% of them still show up with the whole sequence. And we do the full analysis and we look at it,

but it'll take me a while to remember the last time a piece of information emerged from that that made me change the way we were doing something, which doesn't mean it won't happen. It just means overall the yield is not that high and one should sort of calibrate their expectations for that. Well, along those lines, so another snip question. Do you think those SNP's panels, like 23 and me, are useful for practice of longevity

tactics? And what are the 8-12 genes that increase longevity that you always talk about? You can find all of this information and more at pterotiamd.com forward slash podcast. There you'll find the show notes, readings, and links related to this episode. You can also find my blog at peteratiamd.com. Maybe the simplest thing to do is to sign up for my subjectively non-lame once a week email, where I'll update you on what I've been up to,

the most interesting papers I've read, and all things related to longevity, science, performance, sleep, et cetera. On social, you can find me on Twitter, Instagram, and Facebook, all with the ID, peteratia, you can find me on Twitter, Instagram, and Facebook, all with the ID, Peter, ATF, MD. But usually Twitter is the best way to reach me to share your questions and comments. Now for the obligatory disclaim. This podcast is for general informational purposes only and does not constitute the practice of medicine, nursing, or other professional

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