Can You Slow Aging With Epigenetics? - Dr. Michael Ruscio, DNM, DC

Can You Slow Aging With Epigenetics?

How Diet and Lifestyle Can Turn Back the Biological Clock with Dr. Kara Fitzgerald

Advances in epigenetics show exciting potential for helping to treat disease and slow the aging process.

Podcast guest Dr. Kara Fitzgerald has made an important contribution to this field with a new study of epigenetics and aging. Her groundbreaking clinical trial found that biological age can be reversed by more than 3 years by introducing simple diet and lifestyle modifications. In short, genetics do not necessarily determine our health destiny.

Listen to our discussion and prepare to have your assumptions about aging and disease challenged.

In This Episode

Episode Intro … 00:00:45
The Background of Epigenetic Expression … 00:04:10
Methyl Donors & Evidence of Need … 00:08:06
Epinutrients: Methyl Donor Rich Foods & Polyphenols … 00:09:42
The Pilot Study & Helfgott Research Institute … 00:15:16
The Power of Interventions & Agouti Genes … 00:18:52
Polyphenols, Whole Food Extracts & Supplement Dependency … 00:23:38
Study Findings: A Pilot Randomized Clinical Trial … 00:34:38
Validation, Epic Array, and DNA Methylation Clocks … 00:45:35
Episode Wrap-Up … 00:48:26

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Hi everyone. Today I speak with Dr. Kara Fitzgerald (drkarafitzgerald.com), who excitingly just published a study and has a coming book expanding upon this study that found a dietary and lifestyle-based intervention was able to reduce aging, as measured by a validated measure for aging — actually reducing aging in this cohort after eight weeks by three years. And one of the main mechanisms was through modulating methylation. However, there are one or two other key points I want to flag for you here that we will hit in the body of the discussion. As Kara has mentioned on the podcast in her prior appearance, over-methylation can be a problem. Taking high doses of vitamin isolates for a long period of time can be problematic. However, there are some food-based agents like turmeric, green tea, and rosemary that could loosely be termed as methylation adaptogens that are safe and beneficial in the longer term.

Those are a few main remarks I wanted to give you for a sense of what this podcast is about. Again, I just want to thank Kara for publishing a randomized, placebo-controlled trial — which is great science — and really validating that approach is very central to functional medicine. These dietary and lifestyle-based interventions can, in this case, lead to a reduction in aging after eight weeks. They documented over a three year reversal of biological age. We also want to be careful with not thinking that because we can test for some facets of methylation, and some of these snips impact methylation, that we should be taking methyl-donor supplements in high doses for a long time. That actually might be counterproductive. And with that, we will now go to the conversation with Dr. Kara Fitzgerald, her study, and corresponding book – Younger You. Okay, here we go.

➕ Full Podcast Transcript

Episode Intro:

Welcome to Dr. Ruscio Radio, providing practical and science-based solutions to feeling your best. To stay up to date on the latest topics, as well as all of our prior episodes, make sure to subscribe in your podcast player. For weekly updates, visit drruscio.com. The following discussion is for educational purposes only and is not intended to diagnose or treat any disease. Please do not apply any of this information without first speaking with your doctor. Now, let’s head to the show.

Dr. Michael Ruscio:

Hi everyone. Today I speak with Dr. Kara Fitzgerald (drkarafitzgerald.com), who excitingly just published a study and has a coming book expanding upon this study that found a dietary and lifestyle-based intervention was able to reduce aging, as measured by a validated measure for aging — actually reducing aging in this cohort after eight weeks by three years. And one of the main mechanisms was through modulating methylation. However, there are one or two other key points I want to flag for you here that we will hit in the body of the discussion. As Kara has mentioned on the podcast in her prior appearance, over-methylation can be a problem. Taking high doses of vitamin isolates for a long period of time can be problematic. However, there are some food-based agents like turmeric, green tea, and rosemary that could loosely be termed as methylation adaptogens that are safe and beneficial in the longer term.

DrMR:

Those are a few main remarks I wanted to give you for a sense of what this podcast is about. Again, I just want to thank Kara for publishing a randomized, placebo-controlled trial — which is great science — and really validating that approach is very central to functional medicine. These dietary and lifestyle-based interventions can, in this case, lead to a reduction in aging after eight weeks. They documented over a three year reversal of biological age. We also want to be careful with not thinking that because we can test for some facets of methylation, and some of these snips impact methylation, that we should be taking methyl-donor supplements in high doses for a long time. That actually might be counterproductive. And with that, we will now go to the conversation with Dr. Kara Fitzgerald, her study, and corresponding book – Younger You. Okay, here we go.

DrMR:

Hey everyone. Welcome back to Dr. Ruscio Radio. This is Dr. Ruscio here with Dr. Kara Fitzgerald who has some exciting news on a study she just published. A lot of media attention is being given to this study regarding healthy aging, but there’s a lot more to unpack. Kara – congratulations on the study and the publicity. It’s great to have you back on the show.

Dr. Kara Fitzgerald:

Thank you. And Michael – it’s always really lovely to talk to you and catch up with the amazing things you’re doing in your world, so thank you for inviting me back.

DrMR:

Yeah. It’s always a pleasure to chat. One of the things we share is this split role of clinician and researcher, so we always connect on that level. It’s nice to nerd out with you in that regard. Tell us about this study. There is so much here to unpack. I want to steal all of your thunder here and tell people everything about this study. Give us the overview.

The Background of Epigenetic Expression

DrKF:

Sure. Just stop me at anytime. I’m completely comfortable with being interrupted if I need to clarify anything. I’ll give you a little bit of the background. I started to really pay attention to epigenetics in about 2013. Or at least I started to metabolize the science around it. To be honest with you (and maybe this is a foreshadowing of how much it was going to change my existence), I was a little bit resistant to dive into the literature, but it continues to be produced at a breakneck pace. Extraordinary volumes of science are being released on looking at epigenetic expression and what influences it.

DrKF:

Back in 2013, the big studies that I was looking at in the dominant area of investigation was in cancer, in oncology. The tumor microenvironment hijacks epigenetic expression. The tumor microenvironment takes over our genetic expression, if you will, as scary as that is. And if I don’t say it later, I want to say that other chronic diseases of aging do, as well. You see these changes happen that are sort of consistent across disease processes. And they’re also shared with aging. That’s a little bit of where I’m going to be going, but cancer is the best studied. And of the epigenetic marks, of the way that we regulate gene expression through epigenetics, the most investigated and arguably one of the most important mechanisms is DNA methylation. And so very simply – methyl groups are placed on certain regions of the gene or they’re actually inhibited from being laid down. When there are a lot of methyl groups – you can just visualize this – the carbon and three hydrogens is the methyl group.

DrKF:

And when there are a lot on a promoter region of a gene, that gene cannot be turned on – it’s inhibited. Conversely, when there are no methyl groups, that gene is able to be transcribed and proteins produced from it. So, cancer turns off good genes – like tumor suppressor genes that surveil us and keep us cancer-free, take care of DNA repair, etc. They have all sorts of really important roles, actually. Glutathione S-transferase is a classic tumor suppressor gene, and it can be hypermethylated and turned off in cancer. And we know that’s a really important detox gene. A lot of important genes can be taken over by cancer. And so here I am reading this, finally, after being a little bit resistant back then.

DrKF:

Let me just say that cancer will turn off good genes and turn on bad genes. I’m being very simplistic here. So, oncogenes – genes that will let cancer go forward – are hypomethylated and turned on. So, the big question for me as a functional medicine clinician is — Could any of our functional medicine interventions (this was a huge overriding question for me back then) be harming our patients? Since this imbalanced methylation is happening in cancer (this was my first inquiry), if we’re giving somebody very high dose methyl donors, could that be a problem in somebody who might have an early pre-cancerous condition? Could we be moving methylation in an imbalanced way in epigenetic expression? And it really stopped me in my tracks, Michael. It really did.

Methyl Donors & Evidence of Need

DrKF:

And I looked a little bit further and I do talk about this in the book. I actually go into relatively great detail that the answer is maybe, especially as we get older. We know we need loads and loads of methyl donors. There’s no argument with it there. And when we’re really frankly deficient – like your patients where I’m imagining a lot of SIBO folks need B12 and so forth because they can’t absorb it – there are times when we really want super physiological amounts of these nutrients, but do we keep giving them whether there is an evidence of need or not? We might have a single nucleotide polymorphism and we’ve read that extra B vitamins are important. Well, I would say no. I would say that unless we have evidence of need, we want to be mindful about isolated nutrient supplementation, without evidence of need.

DrKF:

And there is some suggestion that we might be pushing cancer forward. Most famously, there was a study looking at a low dose amount of folic acid and B12 in preventing fractures. In fact, they saw (on repeat analysis) over a period of years, a significantly increased incidence in colorectal cancer, especially in older people. That was one of the speculated mechanisms wonking out methylation.

Epinutrients, Methyl Donor Rich Foods & Polyphenols

DrKF:

Anyway, I have an amazing nutrition team here, as you know. And my founding nutrition director at that time – Romilly Hodges – she and I really got to dialoguing about this. And we decided to build out a diet and lifestyle plan that would support balancing methylation. There is nowhere in the literature that shows a food-forward approach with a heavily methyl donor rich diet is associated with cancer.

DrKF:

In fact, most often the literature shows that it is protective against cancer. So, we built out this diet program that’s very dense in methyl donors. Additionally, there are these epinutrients – these methyl donor rich foods like liver, eggs, beets, leafy greens, mushrooms, pumpkin seeds, sunflower seeds, and on and on. And then there’s this other class of nutrients that we’re calling methylation adaptogens, but they’re also epigenetically active. You can call both of them epinutrients, if you want to. And these are all of the polyphenols that we know and love – like turmeric, EGCG in green tea, rosmarinic acid in rosemary, luteolin, lutein, resveratrol, etc. These guys are not methyl donors, they’re not in the methylation cycle, but they seem to be directing where we put those methyl groups on DNA.

DrKF:

They, in general, inhibit or augment DNA methyltransferase activity. There are a host of in vitro studies and some animal studies (it’s a new area, epigenetics in general, in this regard, is new) that shows they allow for re-expression of good genes. It makes sense when you look at the history of these polyphenols. They’ve got long, time immemorial use histories in classic medicines around the world… or in traditional diets around the world. And they’re just healthful and they have a wide variety of influence. Well, they influence us with regard to gene expression. So, we created a diet that was loaded up in both with the idea that the methyl donors are needed in abundance, but they need to be supported in where and how and what they do. And maybe it’s these polyphenols that are actually influencing that journey.

DrKF:

We zoomed out further in the science and saw other variables. In our field, we got a little myopic with focusing on the methylation cycle because there are far many more influencers — exercise, sufficient sleep, stress reduction, meditation, etc. All of these things have influence on genetic expression, and specifically DNA methylation. The science is out there and more and more is out there in humans. It’s just really impressive. And so we put it all together and we started to use it in our practice. We saw favorable results, clinically. Romilly and I were just scratching our heads (like I know you do in your practice) thinking — How can we actually research this? This was 2016 and we released it as an e-book and we lectured on it, too. I lectured on it to colleagues and people were pretty interested in it, but how do we actually put some science behind this?

DrKF:

Well, if you wanted to look at epigenetics at that time, you can’t order a lab through Quest. You still can’t. In 2017, the only way we could actually research it was to enter the research setting and ordering a specific array from a research laboratory. We ended up getting a full grant on that through Brent Eck, the CEO of Metagenics – a full, unrestricted grant. This means that they did not control our study design, nothing. We were able to actually put our diet and lifestyle to the test to see how we were influencing genetic expression and specifically, DNA methylation.

DrKF:

Now, the aging question — So, we entered into the whole longevity question through the lens of thinking about cancer and cancer epigenetics. Now, this goes back to the beginning, and then I swear I’m going to shut up. We entered into the conversation through cancer, but aging is the biggest risk factor for cardiovascular disease, for cancer, for diabetes, for dementia. Aging is the biggest risk factor and they share these DNA methylation imbalances. And so as we put our study together, the questions evolved and we still have a lot of data to analyze. And I can share with you later, if you want to, some of the preliminary other findings that we’ll be publishing on, but the question on whether we could reverse biological age became central to our investigation.

The Pilot Study & Helfgott Research Institute

DrKF:

It’s a pilot study and studies are expensive. These are really big things you learn when you don’t do studies – you armchair quarterback studies – and then you actually get in there and run one. It’s such a different animal, but we’re grateful for the financing to have a randomized control trial where half of the men of the 40 men did the intervention – this diet and lifestyle program. We had our nutrition team meet with the participants about weekly. And then we had a control group who only got the testing. And we hired the Helfgott Research Institute at my alma mater, National University of Natural Medicine out in Portland, Oregon. We hired that institute to run our study. And my co-PI is Ryan Bradley, who is the director at Helfgott.

DrKF:

It ran for eight weeks. We had a rolling enrollment. We found cholesterol was lowered… LDL was lowered… methylfolate was significantly increased. We saw some other interesting biomarker changes in that regard, but the big aha and what’s garnered the most attention is that it’s the first study of its kind to show a 3.23 year biological age reduction, as measured by the Horvath DNAm age clock, as compared to our control group. So, our study group within eight weeks time got over three years younger. And now I’ll stop. Michael, I’ll let you jump in.

DrMR:

Yeah. So much there to unpack. Let me try to work through some of those things. There is a tremendous amount there that I think is worth echoing. Going back to one of your first comments — this is something I appreciated about the way you were approaching methylation way back at the inception. Once methylation took off, it seemed like no one was really talking about it, and then everyone was talking about it. As things tend to go, unfortunately, there is this more is better mentality, which I partially get. I think we all want to believe that more is better. At least part of our mind wants to think that if a little makes me feel good, a lot will make me feel great. That might be partially human nature, but it has to be bridled by that scientific or cautious part of your mind.

DrMR:

And this is what I really appreciated about the way you approached methylation. You were the first person I heard make the remark that too much methylation could be a bad thing, and really trying to sound the alarm bell that high dose methyl donors may be a bad idea. You may actually end up turning on cancerous genes and we should be doing this further upstream with diet and lifestyle interventions. I just want to echo that because I still have people walking into the office who say things like “I’m MTHFR positive” and they’ve been gobbling up all sorts of high doses of folate or B12 or whatever else, in some cases for years. Because of that one snip, they have to be doing this forever. I try to tell them – please do not do that, but I think it’s hard if you’re swimming against the current of messaging on the internet. So, maybe just to echo that one point for people so they’re clear that there is such a thing as too much methylation, even if you had something like a MTHFR positive. Anything you want to add on that? There are a number of points I want to get to, but that one I think is worth just re-echoing.

The Power of Interventions & Agouti Genes

DrKF:

Absolutely. It’s so important. I want to say two things. I want to make it clear to people that this doesn’t mean that you then turn around and throw away all your B vitamins either, but you want to be working with somebody you trust who understands these nuances because there is a time and a place. I would argue that we probably don’t need the gram amounts that we’ve been taking either. They’re potent. Dr. Randy Jirtle and Dr. Robert Waterland in their original agouti mouse study really saw this, so they turned off the agouti gene. They gave pregnant mice the methyl groups – the betaine, folate, and B12. They gave this to them in their chow and they shut off this agouti gene, which was a good thing.

DrKF:

The agouti gene makes mice very distinctly obese and blonde, and then they’re vulnerable to all the associated diseases when this agouti gene is on. They were able to methylate it and restore the offspring of these agouti mice to the wild type brown mouse. They call them pseudo agouti. It’s extraordinary. And it’s validating to us in nutritional medicine to see the power of our interventions, but if you pull that original paper up, they don’t end with how extraordinary nutrients are. They end with a caution on look how powerful these guys regulate genetic expression. We need to be careful. That’s their pause way back in the day. And I don’t think we quite heard it because we were so excited with how validating it was to see nutrients. And they were like – we actually want to be mindful of their power. And I think I see that. I appreciate that now. It’s not to say you never take them, but in the age of ‘omics where we can actually start to see what genes are on and off and in what patterns, the appreciation for the power of our interventions can’t be understated.

DrMR:

Right. Thank you for that. I think that is important for us to echo.

Dr. Ruscio Resources:

Hi everyone. Just a quick announcement regarding the clinic. I am happy to say that I, and we, at the clinic are now offering a free monthly support call to all current patients. This applies to any patient at the clinic, even if you’re not working with me directly. This is an opportunity to ask me and our team questions, share feedback, and get support with any challenges you may have. I will be accompanied by Dr. Joe Mather, our medical director, and Morgan Molidor, our clinical health coach. We have emailed details to all of our patients, so check your inboxes. And here is Erin with the date and time of our next call. Hope to speak with you there. The next call will be Friday, March 11th @ 1:45 PM central.

DrMR:

You drew this line between the methyl donors and the methyl adaptogens, and it would appear (and please correct me if you have a different position on this) that the best way to get both of these is through diet. Do you think there’s more leeway, perhaps, with the adaptogens? If they are truly adaptogenic, then they tend to bring you back to center. If someone was going to take a long-term, high dose B12, it’s maybe not a good idea outside of certain exceptional cases, whereas using a turmeric supplement or a resveratrol supplement. Are those less prone to inflict harm if taken in a supplemental dose in the longer term?

DrKF:

That’s a great question. That’s a really good question. I want to say a couple things. They are, in and of themselves, some have science that that they’re adaptogenic – meaning that they can either promote or inhibit methylation – and actually curcumin is one. In general, we’re calling them adaptogens in how they work with the methyl donors.

DrMR:

So, it’s a loose description…?

Polyphenols, Whole Food Extracts & Supplement Dependency

DrKF:

It is. And probably if I were to rewrite this again, I would call them epinutrients. I would call both groups epinutrients. It’s a loose term, but you can think of them as traffic directors in the context of adequate methyl donors. That said – yes! I’m inclined to agree with the idea that we can take these polyphenols as standalone interventions. We did give a greens powder, so we did a concentrated polyphenol powder in our participants. And we did see favorable changes. We did a greens powder and we also gave a probiotic, as well – Lactobacillus plantarum. I am inclined to agree that they’re favorable, and I would also suggest that we should use these most probably as extracts of whole foods.

DrKF:

Again, take it in a whole food product. Just be mindful of that. I don’t know that I would isolate and standardize curcumin and take a ton of it long-term. Take a ton of it for your back pain, for the inflammation you’re working on, etc., but look to whole food sources – even concentrated amounts encapsulated. I do not drink a lot of green tea. I don’t. I’m sorry, folks. Anybody who follows me knows I’m Team Coffee, but I take green tea. I do.

DrMR:

Me too.

DrKF:

You are? <laugh> Yeah, I am. I like coffee, but you cannot underestimate the green tea collection of polyphenols. They’re just beautiful and important, and so therefore, I take green tea extract. I think that is the better way to deliver those catechins versus just an isolated EGCG product.

DrMR:

This is helpful. Just using myself as someone who at one point didn’t feel well, supplements were part of what I used to improve my health. However, I think we can very easily fall into this false, but expected dependency upon supplements. Let’s just use resveratrol as one example. If that was being used in the context of a gut intervention where perhaps there was SIBO and this person used a high dose probiotic along with a low FODMAP diet and resveratrol, and that was enough to improve how they were feeling, there can be this fear of coming off of the resveratrol. You associate feeling good to that – myself included, not picking on anyone. I’ve felt this pull myself where I’ve been reticent to come off supplements. I’ve had to go through the exercise of just cutting doses down and cutting things out.

DrMR:

We do this at the clinic, of course, and I preach that this is something that clinicians should do. Again, speaking to the fact that there seems to be this gravitational pull toward more – “well, why not take it. It can’t hurt me. I might as well just use it.” I think what’s so important to call attention to in this conversation is that there may be some harm. God forbid if we learn in five years or so that there’s a pluming of cancer cases in certain realms where supplements were being used in a robust fashion, that would be a real travesty. I mean, I don’t want to put alarm in anyone’s heads, but that’s a potential thing we could be contending with.

DrKF:

Yeah. And in this era of isolating a single compound within a whole food, we run the risk of that. We enter into drug territory really readily.

DrMR:

Yes. And I think that’s how we should be looking at these things.

DrKF:

Yes.

DrMR:

We can’t have it both ways. Natural medicine can’t say, “Hey, what we do is powerful. It can be as powerful as drugs. Look at this one trial that found this natural compound was as effective as this drug.” And then say, “… but the natural things have no side effects. You can take as much as you want for as long as you want.” We can’t have it both ways.

DrKF:

That’s right. If you’re doing your polyphenols and you’re taking them as an extract of a whole plant… or turmeric that’s standardized for a certain amount of curcumin… I think you’re on safe territory. One of my favorite polyphenol combinations now is the Himalayan Tartary buckwheat that Jeffrey Bland has been talking about. It’s just an extraordinary epinutrient rocket fuel, actually. I’m pretty excited to do more research on that, but it’s a whole food. It’s just popped in capsules for lazy people like me who haven’t yet made Himalayan Tartary buckwheat muffins or something like that. I think you’re on safe ground with that, but B vitamins are synthetic. They might be bioidentical, but we only isolated them in the last century. Before that we used liver, Michael. We used liver and that’s a food that we recommend.

DrKF:

That’s a food we actually consider to be a superfood. It’s in a whole food matrix. You can get your day’s supply of B12 easily and a load of folate in this matrix if you eat some B12. That’s how we treated pernicious anemia and B12 neuropathy, etc. not that long ago. I think you’re right. I was certainly taught in medical school that B vitamins are water soluble and you peed them out. There’s no worries. In our world, we were perhaps over-prescribing and then in the conventional medical world, they were like, “Well, you’ve got enough B vitamin in your liver for your lifetime, so you don’t even need to think about taking them.” And then we were sort of dosing in excess. I think the truth is somewhere in between. So yes, we do need them. Some of us need them more. There are certainly times when we want to go to those super physiological doses, and even deliver via injection or IV. I think all of those are fair and we absolutely want to be mindful in understanding that they play a role in epigenetic expression in one of the most important processes – DNA methylation.

DrMR:

Fully agreed. I’m actually going to update some of what I’m doing in my personal supplementation even further in this direction, and also at the clinic. We’re already pretty far down that road of using higher dose isolates in the shorter term and then helping people find the minimal effective dose, and also having the expectation that they’re not going to need all these things forever so they don’t placebo themselves.

DrKF:

Yes, yes, yes.

DrMR:

And just one thing I’ll throw out for people — At the clinic, when patients ask me if they should be on a multivitamin long term, my response is something along the lines of “You probably don’t need it. If you wanted to take a bottle of a multi-vitamin every few months, just as a hedge, that seems like a reasonable in-between for me, where I don’t see that running a risk of overdosing. In case there are some holes in your diet, that might be a decent strategy.” It’s a little bit vague, but I’ll check that with you here, Kara. Do you feel like that’s going even too far in the direction of allowing these isolates to be used?

DrKF:

Well, no. I think that is really sound advice. I agree with it. What’s funny is that as you were talking, I was just about to write down a note to self. The best way to know in my world, coming from the clinical laboratory setting, we used to measure all of everyone’s essential and conditionally essential nutrients. That’s what we did at MetaMetrics. We did that. You want to know how much magnesium you have? You can test for it. I have a new report on all my essential and conditional essential nutrients. I had it done not too long ago and I need to actually adjust my treatment plan… adjust my nutrient intake based on it. I’ve been so distracted with other stuff, so as you were talking, I was like, “oh, I need to look at that. I know I have some things I have to shore up.”

DrKF:

We all have nutrient insufficiencies and we trend in and out of deficiency based on need. I’ve never not seen that in looking at thousands and thousands and thousands of reports over my career. We all have needs — if we’re stressed out… if we’re metabolically active… if we’ve decided to take up a really intense exercise schedule, we even need more… if we’re recovering from a surgery… whatever is going on. If the COVID isolation has played havoc on our mental health, we probably need certain nutrients a little bit more than others. And so, a periodic multivitamin – or taking a multivitamin a couple days a week – is a really good idea.

DrKF:

I’ve got an Oura Ring on and often I’ll have a continuous glucose monitor on. I enjoy that being a data hound, but in this age of wearables combined with our ability to start looking more and more at gene expression, we’re going to be able to see what nutrients we need and see how they’re expressing gene expression. It’s going to become more of a routine exploration in our lives. And that will guide us around what’s right for me and what’s right for you and so forth.

DrMR:

A few things there I want to pick your brain on, but before I jump there, I want to make sure we don’t gloss over the study just to make sure that we report your finding. There were 40 men (20 treatment + 20 placebo) for an eight week intervention. And what was the intervention that the treatment group got?

Study Findings: A Pilot Randomized Clinical Trial

DrKF:

They followed a diet. I want to say that this is a free, full text, so people can look at the details of what we prescribed (https://www.aging-us.com/article/202913). The diet is very rich in methyl donors. It’s low glycemic. It’s got these methylation adaptogens, so colorful fruits and vegetables. It’s got green tea, garlic, turmeric, etc. It’s low glycemic and it’s keto leaning. They burned a lot of triglycerides, so they were probably in a gentle ketosis. There is very moderate time restricted eating – only a 12 hour on/off window. It’s so doable. We wanted them to be well hydrated. We didn’t insist on eating organic, but we did encourage it. We wanted them to use glass, not microwave and plastic, etc. We gave them some basic guidance there, not particularly onerous.

DrKF:

They did a greens powder. They used the Metagenics PhytoGanix greens powder, which is an organic veg combination. And then they took Metagenics UltraFlora Intensive Care, which has lactobacillus plantarum. The reason we gave lactobacillus plantarum is there’s some suggestion that it supports synthesis of microbiome produced folates. That’s another area, which of course you know very well. We can make loads of vitamins in a healthy gut, and so we wanted to lean on that as well.

DrKF:

We wanted a simple exercise prescription: 30 minutes, at least five days a week, at an intensity of 60% – 80% of maximum perceived exertion, doing whatever they want. A lot of the guys opted to walk to work or take a walk in the evening. These were very healthy men, by the way. We weren’t working with people who had any kind of diagnosis.

DrKF:

There was a pretty extensive exclusion criteria. We wanted to look at healthy, middle-aged, guys because we see DNA methylation get wonky with aging. We see DNA methylation patterns changing in a negative way. We become more vulnerable to the chronic diseases that I talked about earlier. We wanted to look right in the heart when those changes start happening — our population was 50 to 72. We had them do a basic exercise prescription. They were healthy guys, so some of them had to back off of what they were doing rather than turning it up. Some of them were really active exercises and I don’t have a problem with that. It’s just that in our study, we had to draw a hard structure.

DrKF:

We wanted them to get a minimum of seven hours of sleep per night, and we gave them sleep hygiene tips. When the nutritionist met with them, they would brainstorm on going to bed earlier, making sure the room was dark, nothing crazy. And we prescribed a meditation. Specifically, we used breathing exercises — steps to elicit the relaxation response that was developed by Herbert Benson out of Harvard. It’s a very simple breathing exercise that we prescribed twice per day at a minimum of 10 minutes per session. And that is it.

DrKF:

It took us a while to recruit. It was an involved study. An interesting side note — Ryan Bradley studied us administering the study because the protocol is involved and he expected touchy adherence, not necessarily great adherence. He paid attention to that. And we actually got, I think, very good adherence. I think participants were excited to be looking at really the first (at that time) diet and lifestyle intervention in a controlled study in epigenetic expression. I think they were jazzed up about that, but also having the nutrition team meet with them. They couldn’t cheerlead. The nutrition team could not go in and do like we do as clinicians and support our people to the finish line. They had to read from a really dry script. I still think that consistent interaction helped.

DrKF:

And honestly, Michael, I was like, “We’re making this happen you guys because nobody else is going to be gifting me hundreds of thousands of dollars to be able to launch this.” I knew it was a really special opportunity, and I just wanted to ensure the best possible outcome. And we did achieve that.

DrMR:

This, of course, is something that probably sounds very familiar to many people in our space. These are the core essentials of what we advise people to do — sleep hygiene… exercise… breathwork… meditation… healthy diet… so it’s just so fantastic that we can document the power of these fundamentals that are sometimes glossed over because they’re mentioned so ubiquitously in a healthcare conversation. I applaud that. I think that’s absolutely fantastic.

DrKF:

When you get into the science and you start to look at how meditation influences biological aging influences gene expression… or when you look at exercise… Let me tell you this. I told you earlier that polyphenols support the re-expression of the all important tumor suppressor genes. Tumor suppressive genes in cancer get hypermethylated and shutoff. In aging, they get hypermethylated and shut off. It’s a raw deal. What the heck is this with aging that good genes are shut off and bad genes are turned on. It’s nuts. And there’s thinking that this might be a programmed process for evolutionary reasons. As I sit in the epigenetic science, it makes sense.

DrKF:

So, exercise acts like polyphenols. It re-expresses these tumor suppressor genes, and so you see the science all over the place in really exciting ways. You see the damage that poor sleep does – even one poor night will have epigenetic ramifications. It’s consistency though over time that can really lead to lasting changes, either favorably or negatively. And one other thing – you’ve got me so excited about this – is that these patterns are heritable. Going back to exercise, you can hand down gene expression consistent with beneficial effects of exercise to our offspring. It’s nuts.

DrMR:

I love it. And this is part of the reason why I’ve been going pretty deep into sleep health. We’ve been using these home sleep tests that can pick up what I’m loosely labeling as these subclinical or mild apneas. Or in some cases, they’re not even apneas. They’re actually just an increase in this parallel measure called the Respiratory Distress Index. There was one study that actually found that there were worse outcomes for those with elevated respiratory distress indices, even if they didn’t have apnea and actually was worse in some cases than apnea. So, we’ve been using things like myofunctional therapy and sleep devices.

DrKF:

So smart.

DrMR:

I’m hopeful that there’s this subset of people where they don’t have glaring apnea, where they feel like death. That is a fairly easy target, but it’s those people who say “… I feel good, but my memory could be sharper. My energy could be higher. I’ve got to do everything just right to feel at 100%. And when I’m at that 100%, it’s great, but the littlest push throws me off…” It’s too early for me to say — we’re still mid-intervention with a handful of people — but I’m excited about that for those reasons… because of the massive impact of sleep. I share your excitement.

DrKF:

You’re not quite the testing geek that I am, but if you’re interested, it would be really neat to look at epigenetics in one of your studies at some point.

DrMR:

Let’s put that on the board. I’m doing personal experimentation here, and we’re also integrating this into the clinic; trying to develop a sleep algorithm in terms of what’s the best assessment, what’s the best interventional hierarchy, what things have a good cost benefit analysis – all these things that we’re mapping out. What does the post-intervention subjective improvement look like, as compared to the objective re-testing parameters? I think it’ll probably take me another six months to have a good handle on this, but then once I do, I was already planning on doing a small cohort pre-post assessment with an objective measure/subjective measure, but to do some sort of genetic or epigenetic assessment along with that, that would be really cool.

DrKF:

Okay, cool. Just definitely reach out to me. I’m hard at work, God willing will be able to manifest an array that’s got a really affordable price point. We’ll just stay in contact with that. I would love to support you.

DrMR:

Beautiful. Love it.

Dr. Ruscio Resources:

Hi everyone. If you are in need of help, we have a number of resources for you. Healthy Gut, Healthy You – my book and your complete self-help guide to healing your gut. If you’re not a do-it-yourselfer, there is the clinic – The Ruscio Institute for Functional Medicine – and our growing clinical and supporting research team will be happy to help you. We do offer monthly support calls for our patients where I answer questions and help them along their path. Health coaching support calls every other week. We also offer health coaching independent of the clinic, for those perhaps reading the book and/or looking for guidance with diet, supplementation, et cetera. There’s also the store that has our elemental diet line, our probiotics, and other gut health and health supportive supplements. And for clinicians, there is our FFMR – The Future of Functional Medicine Review database – which contains case studies from our clinic, research reviews, and practice guidelines. Visit drruscio.com/resources to learn more.

Validation, Epic Array, and DNA Methylation Clocks

DrMR:

One of the things I wanted to ask was – What was this gene measure? And what does it tell us? Has it been validated? And did you correlate this with anthropomorphic measures or subjective measures like fatigue or sleep quality?

DrKF:

Sure. All good questions. Yes, we used the Illumina Epic Array. It is a massive and it measures the methyl alone, so all of those methyl sites on the DNA — close to a million of them. Illumina is the premier laboratory producing methylation arrays, and they’ve been doing so really longer and more reliably than anyone out there, I think. Although, there are other good labs, too. I don’t want to isolate or put anybody else down. We had Yale process our data, and then we worked with McGill University. I also worked with Josh Mitteldorf, who is a biostatistician for analyzing our clock data. There are plenty of publications using the Epic array that we used – plenty… many, many, many out there and the arrays that preceded the Epic, so they keep getting larger and larger. Prior to that, there was a 450.

DrMR:

And the reason I ask here, just really quick, is there are some tests out there… I think uBiome was a good example of this. I don’t mean to pick on them, but it just received such publicity that they didn’t really go through validation…

DrKF:

Oh, I got it. This is only available in the research setting. This is not a direct-to-consumer test by any stretch. This is only in the research setting. And the clock that we used is the flagship, best published DNA methylation clock that was created by Steve Horvath out of UCLA. The clock that we used is the first generation biological age clock, and it correlates with chronological age very rigorously. People can read about it. I know we don’t have a whole lot of time, but you can read about it. It’s been very well validated and well published.

DrMR:

Perfect. That’s the main thing I’m after — that this is not something where 20 people at an office took a test and that was their evaluation…

DrKF:

That’s right. And we talk about what it is and what it does in the study. There are next generation clocks that are coming out. It’s a really exciting and fast moving field, but you can read exactly what we did and what the science is behind it in my book, which will be out January 18th, 2022.

DrMR:

Tell us the name of the book, and then where people can learn more. There’s probably a website?

DrKF:

You can learn more about the book at www.youngeryouprogram.com. The book is called ‘Younger You: Reduce Your Bio Age and Live Longer, Better.’ It’s written in plain language. If any of this was Greek to you tonight, I actually wrote the book with Kate Hanley who helped to translate all of my gobledygook into user friendly language. It’s just exactly how to do it. And if you want to, you can access the app. You can find the app also at youngeryouprogram.com and the app will completely hold your hand through it down to getting the epigenetic testing, to working with the nutritionists, including some that were part of the study. So both of those are at youngeryouprogram.com. Or if you forget that and you just go to my site at drkarafitzgerald.com, you’ll get directions over there if need be.

DrMR:

Love it. Also, the title of your study was ‘Potential reversal of epigenetic age using a diet and lifestyle intervention: a pilot randomized clinical trial’ just to flag that for the clinicians there, in case they want to look that up. The one other thing I just want to get your perspective on was — Was there any sub-analysis or correlation between subjective measures or body composition indices that correlated with the clock?

DrKF:

Other than what I mentioned earlier — triglycerides dropped, LDL dropped total cholesterol dropped, folate increased in our study participants -there were no significant subjective changes. And we looked at quite a few. There was a little bit of change towards less fatigue and so forth, but I want to say (and this is an important point), these guys were healthy.

DrMR:

Right. I was just going to say that’s probably hard to get more improvement or enhancement in that cohort.

DrKF:

Yeah. They were healthy. And I think the fact that we were able to move them favorably and they started healthy…

DrMR:

Great point. It bolsters the strength of your finding in the sense that you were able to show this anti-aging effect ostensibly. If you followed them for five years or so, you’d probably see less disease in one of the cohorts, I’m assuming, based upon some of what you said. We can look at this as a preventative finding, it sounds like.

DrKF:

Hopefully they’ll stick with some. The folks we’ve communicated with do. Hopefully they’ll stick with some of these habits. I think if they do it as an isolated eight week intervention, and then decide to adopt a McDonald’s diet (which they won’t because they started out healthy), but…

DrMR:

Not this cohort.

DrKF:

It’s exciting… exciting stuff ahead in this whole area of investigation.

DrMR:

This is great. Well, Kara – I know you’ve also been receiving a lot of media attention on this. Anything you wanted to just share there quickly?

DrKF:

It’s so exciting. It is really exciting. When the study came out, it got a ton of attention, both in the scientific community, as well as in the mainstream community. I was thrilled, and really somewhat blown away, when it was written about in Martha Stewart and when The Sun ran a long article and The UK Times wrote two pieces on it. I think it was just really a bright spot in an otherwise really dismal time with COVID. And likewise, with the book, people are excited to have biohacks for the rest of us versus just the wealthy. This is a diet and lifestyle program that we can all do, and I can see that lighting up the media. And so… The Doctors… Rachel Ray… all over the place… Maybe I’ll have appeared on some of those by the time of this broadcast, but it’s just really exciting. It’s exciting to see the New York Post write about it and basically say just that. Jeff Bezos and Tom Brady…

DrMR:

… their anti-aging secrets aren’t these $5,000 a month protocols, per se…

DrKF:

Right. You can do this folks, you’ve got this. And I would argue that we have to get this. The United States is in an accelerated aging trajectory right now. And we have to reverse that, and this is one way we can do it.

DrMR:

I could not agree with that more. I’m going to put three questions on the table that we won’t answer now, but I’m hoping that you won’t be too busy with all these hotshot media appearances <laugh> and you’ll be able to come back on the show. II’d love to – if we do a part two – go further into micronutrient testing and compare some notes there because we recently went into a review of the evidence on this. And so I think that’d be insightful to banter that back and forth. Thoughts on genetic testing, like 23andme — yes or no? If so, how and when. And then also thoughts on NAD. Those are questions I’ll keep on my side and we can hopefully get you in here for a part two. Kara – congratulations on the book, on the research, hopefully on being on national television and making some waves. Any closing thoughts that you want to leave people with?

DrKF:

This should be empowering, so rather than having aging or the diseases of aging driving our genetic expression, this offers us hope that we can get back in there and start; to take it over and do it ourselves and have a vibrant and long life.

DrMR:

Well, I will sign up for that. That’s definitely something I would like to have. Love the research publication… love the book that’s coming on the heels. For everyone in our audience, that’s Younger You (the book) and youngeryouprogram.com (the website/app). Kara – keep up the good work. It’s been a pleasure chatting with you.

DrKF:

Likewise, Michael. Thank you so much.

Outro:

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