What Foods Should You Eat And Supplements Should You Take To Age Well?

Mark Hyman, MD

Dr. Mark Hyman is leading a health revolution—one focused on using food as medicine to support longevity, energy, mental clarity, happiness, and so much more. Mark Hyman, MD is a practicing family physician and an internationally recognized leader, speaker, educator, and advocate in the field of Functional Medicine. He is the founder and director of The UltraWellness Center, Founder and Senior Advisor for the Cleveland Clinic Center for Functional Medicine, a fifteen-time New York Times best-selling author, and Board President for Clinical Affairs for The Institute for Functional Medicine. He is the founder and chairman of the Food Fix Campaign, dedicated to transforming our food and agriculture system through policy.

He is a co-founder and the Chief Medical Officer of Function Health. He is the host of one of the leading health podcasts, The Dr. Hyman Show with 150+ million downloads. Dr. Hyman is a regular medical contributor to several television shows and networks, including CBS This Morning, Today, Good Morning America, The View, Fox, and CNN.

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Full Transcript

Automatically generated. Please forgive any typos or errors in the following transcript. It was generated by a third party and has not been subsequently reviewed by our team.

Introduction:
Coming up on this episode of The Doctor's Farmacy.

Dr. Michael Murray:
If you're looking at wanting to live longer, you've got to have plenty of energy. You have to ask the question, "Well, how do I make sure my energy producing machinery is working properly?"

Dr. Mark Hyman:
Welcome to The Doctor's Farmacy. I'm Dr. Mark Hyman. That's Farmacy with an F, a place for conversations that matter. If you're interested in the field of longevity, as I am, then this will be an interesting conversation. It's with one of my mentors, someone I've learned so much from over the years, who's an icon in the field of natural medicine and functional medicine, Dr. Michael Murray. He's a naturopath, and has written the Textbook of Natural Medicine, which I used a lot as I was starting to navigate a world outside of my traditional training in conventional medicine. He's one of the world's leading authorities on natural medicine. He's written so many important books on this. He's a graduate of Bastyr University.
His textbook, the Textbook of Natural Medicine, which he coauthored with my good friend Joe Pizzorno, is such a seminal work in laying out the science and the methodology of how to apply both lifestyle and other natural therapies to help us heal from chronic disease in ways that really we haven't been able to be able to do before. He's written over 30 books, including the Encyclopedia of Natural Medicine. This is really a very consumer-facing version of the Textbook of Natural Medicine. He's written The Longevity Matrix, which we're going to talk about today.

Since 1985, he's been instrumental in bringing lots of really important and safe natural products to North America, including glucosamine, ginkgo, PGX and lots more. Dr. Murray says one of the greatest myths about natural medicine is that it's not scientific. The fact of the matter is that for most common illnesses, there was tremendous support in the medical literature for a more natural approach, and that's what we're going to talk about today. Welcome, Michael.

Dr. Michael Murray:
It's a pleasure, Mark.

Dr. Mark Hyman:
I just finished writing my book Young Forever about longevity. It was very clear to me that, as I came upon the science of the things that are really working to both make us healthier and live longer, they harken back to the principles of natural medicine. Which is activating the body's own innate healing systems, its own innate healing mechanisms that are embedded in our biology. That are designed to keep us alive and well throughout our lives, but they get honestly trashed by our modern lifestyle.

Dr. Michael Murray:
Right.

Dr. Mark Hyman:
I kind of want to dig into your approach, as someone who's really an expert in this, around the things that you discovered as you were writing your book The Longevity Matrix, and the kinds of things that you found to be most effective. What were the most important strategies from a diet and lifestyle perspective, and maybe some other things. We can get into some of the details, but I want to know, what is the things that kind of were like aha to you that were so powerful?

Dr. Michael Murray:
I'm really looking forward to this conversation, Mark, because I know that we have many parallel experiences. In my book, what I focused on first was a couple of basic things. I look at, what is effective in helping people not only live longer but have a higher quality of life? What I discovered years ago, one of my big aha moments, I was reading a Sports Illustrated article about Stan Musial. This is one of the most beloved sports heroes of all time. He was famous for acknowledging people and showing appreciation. I realized that the people that I knew who were long-lived, that's a polite way of saying old, whom I respected, loved and appreciated, they all had one common feature. They had many different personalities, different routes in their lives, but they shared a common feature.
They had an ease to expressing appreciation, and they lived in a state of grace. Cicero said that gratitude is not only the greatest virtue, but the mother of all others. I started looking at the science of gratitude. There's a whole field of psychology that's just rich of wonderful discoveries. It's positive psychology. Our lives are supposed to be full of such a range of emotions. The ones that we need to feel more of, they really start with gratitude. I look at all the emotions that I truly love experiencing, awe, wonder, excitement, enthusiasm, inspiration. All of these fuel a life worth living, and really fuel us to want to live longer. That was one of my big aha moments, and I'm curious about yours.

Dr. Mark Hyman:
Yeah. It's interesting. So it's not about what you eat or exercise, or any of that. It's not about the right supplements. It's about your mindset, and how you see the world, and how you feel about your life. Whether you're grateful or resentful. Whether you live in a state of joy and connection, or whether you live in a state of regret and hurt and victimhood. I think there's a real phenomena that is biological that gets translated through our thoughts and our feelings. So whatever is going on in your life.
Whether you're a prisoner in Robben Island like Nelson Mandela for decades, but somehow he managed to keep his sense of humanity and his kindness and his wisdom. I mean, we think when our lives suck. Well imagine being on Robben Island in South Africa, and apartheid, and how he survived that. I was just down there, so it kind of reminded me of that when I was in Cape Town. I was like, wow. It's really so much about what goes on up here that determines what goes on in the rest of our body.

Dr. Michael Murray:
Yeah, and here too. I want to make an observation that I've had about you, known to all your viewers and listeners, and they probably noticed this as well. The longest study in history is the Harvard Men's Study. I think the study started in the 1920s, and they looked at men in different socioeconomic levels. What they found was, following these men over their course of their lifetime, the biggest impact on determining health and longevity and happiness and the quality of their lives was the quality of their relationships and their ability to make connections. My observation about you, Mark Hyman, is you are gifted in that area. I really know no one better in making heartfelt, meaningful connections.

Dr. Mark Hyman:
Oh, thank you.

Dr. Michael Murray:
I know you have great connections in your life, and I know that has to be a big aha moment for you. I've known you a while, and I just want to congratulate you on that.

Dr. Mark Hyman:
Thank you. Thank you. It is actually part of the secret of my success, is actually valuing and spending time and energy on keeping, maintaining, developing beautiful relationships across both personal and professional categories. I think you're right. It's really a key part of longevity, which is feeling connected and feeling a sense of belonging and meaning and purpose. I think all that is so true. I want to kind of dig into some of the more practical things that people also want to talk about, which are what the heck should we be eating for longevity? I mean, when you look at the longevity field, you hear everything from, "You should be a complete vegan, because animal protein will kill you, and will drive mTOR and cause an early death."
Or people who are saying, "No, you actually need a lot of animal protein to build muscle and to live a long time." Should you be keto? Should you be vegan? Should you be paleo? What the heck is a longevity diet that you've come up with that makes sense, that incorporates all the scientific research that we do know about how our bodies work and how we age? So we kind of get out of these ideological wars, and come up with what actually is scientifically prudent and sensible, and makes sense.

Dr. Michael Murray:
Yeah, that's very practical. I take a very pragmatic approach. We develop philosophies that sometimes are convenient, but for me it's been a lifetime of discovery. I've gone through different phases of my life. When I first got into health nutrition, I was a strict vegan for six years. Then I started eating fish. Now my diet is, I would say I eat very clean. I don't eat any processed foods per se. One of the dietary principles that I... I had a thought when I was taking physics, and looking through a prism, and seeing a beautiful rainbow. The rainbow diet has kind of gotten very popular these days, but I had this back in the '70s. The idea is that we should be taking advantage of all these different plant pigments in our diet. I have a love affair with a particular type of plant pigments, flavonoids.
There are over 8,000 different flavonoids in nature. As a class of compounds, flavonoids are referred to as nature's biological response modifiers. Let me define what that term means. It means that these plant compounds, these pigments can help modify our response to environmental issues and things that are going on in our body. This is demonstrated by their anti-oxidant, anti-viral, anti-cancer, anti-aging, anti-inflammatory effects and many, many more. Flavonoids are the key components in many foods and medicinal herbs that are responsible for their medicinal effects. I have made a very strong commitment for over 45 years now of eating a diet really rich in flavonoids. I'm taking a lot of supplements. By the way, this is a sample of what I take every day. I take a lot of-

Dr. Mark Hyman:
For those of you who can't see it on audio, it's a little baggie full of stuff, probably 30 or 40 pills in there.

Dr. Michael Murray:
Yeah, exactly. On my website, people always ask me, "What do you take? What do you take?" So I put it on my website, DoctorMurray.com, all the supplements I take, and why. If you look at that supplement list, it focuses a lot on plant flavonoids. Then on my website, I also have an article that I wrote on how to measure your flavonoid intake. How to have a target of what you ideally should reach, and how to get there through dietary choices and supplements. I am a big fan of flavonoids. The great thing is, they are readily available in food. Everyone thinks of blueberries, but red kidney beans actually have higher antioxidant activity, higher flavonoid content than the blueberries. Dark chocolate is a good choice. Raw cacao powder is better.
There's just a lot of secret ways that I've found to really boost my flavonoid intake. No matter what diet that you follow, I think you have to take advantage of these beautiful gifts from nature. The way they work in our body is truly a miracle, because these are highly active compounds. Nature has built in a way that we can ingest them, and they circulate in our blood, bound to various compounds like glucuronic acid or sulfur. What's interesting is they are liberated from those conjugating agents or the compounds they are bound to in areas of need. It really explains how they can be so pharmacologically active, but very safe, because nature has built in a safety profile for them. I like to flood my system with these flavonoids, to make sure that they're there when my cells need them.

Dr. Mark Hyman:
Yeah, that's very interesting. I sort of want to talk about something that's in the field right now, which I don't agree with, but is certainly getting attention. Is that plants have these anti-nutrients. That the phytochemicals in plants are actually poisons, and that we shouldn't be eating them. The whole carnivore extreme version of eating, which is basically just eating meat or animal protein, suggests that these plant compounds are actually harmful.
That all these phytochemicals are the plants' defense mechanisms, and their own poisons per se. They're pesticides, they're herbicides, they're things that repel various predators. We're consuming these, and how are they good for us if they're the plants' defense mechanisms that may be poisons? Is flooding your system actually the right thing, or is there a particular dose that matters? Versus just having a huge amount of, let's say green tea extract, or grape seed extract or something floating around your blood.

Dr. Michael Murray:
These phytonutrients or phytochemicals are really interesting the way they work in our body. Sometimes we get lost in the direct effect, but the fact that they're able to influence the expression of certain genes and the overall impact on our cells, it's pretty hard to argue against them. They really are conductors of a beautiful orchestra that's designed to keep us healthy. I think if we don't consume a diet rich in these foods, we're really doing a disservice. That's not to say that we can't see temporary benefits from following even extreme diets. But I think when you look at what our body needs, it's clear to me that we're really designed to be omnivores. We're not designed to be carnivores. We're not designed to be vegan. We're designed to take advantage of both animal foods and plant foods. There's certain foods that I think promote health more than others.
I think fruits and vegetables, legumes, I think most people are kind of getting away from grains. I do think they have their place, but not so much processed grains. I think we definitely would need to get away from ultra processed foods. That's what the research keeps showing over and over and over. There's a wide berth of what our bodies can consume and be relatively healthy. Likewise, there are a narrow range of foods that we can eat to make us achieve our optimal level of health. I think both of us are kind of living proof of that. We're not separated that much by age. I'm a bit older than you. But like you, I plan to be forever young, if not in body, at least in spirit and attitude.

Dr. Mark Hyman:
Totally It's so true. I think for sure it's also possible to be healthy in body too. I think that's the whole point of this. I want to sort of come back to a little bit more granularity on the nutrition front. Clearly I agree with you. I think a lot of these phytochemicals are important. Many of these work through activating various longevity pathways on our body, these switches that we now are understanding more carefully as we kind of peel back the layers on what we call the hallmarks of aging.
These underlying mechanisms that go wrong as we get older, that are influenced by everything we do, from our thoughts and beliefs like gratitude, but also to the phytochemicals in food, and our exercise, and all sorts of inputs that we can regulate. You wrote this book, The Longevity Matrix. What was your main thesis, what was the main concept behind the book, and what led you to write this book? There's so many books on longevity. I'm just curious about your frame of this, as a doctor who's really an expert in natural medicine.

Dr. Michael Murray:
Mark, I learned something years ago from one of my favorite patients of all time. His name was Dean, and he had a very rare genetic disorder. He was the most compliant, motivated patient I ever had. He said something to me once. I asked him why he was going through all this, because it was a very painful existence. He said, "All I can do is all I can do, so why wouldn't I do all that I can do?" When we look at what constitutes health, if we look at what helps us live a longer and healthy life, it's a constellation. It's a matrix of different factors, different facets. We really have to pay attention to all of them. That's my point of the book. One of the big stress points in the book, something I stress over and over again, just about every major class of medicine that you look at, every class of drug that you look at, it's providing short-term benefit but providing long-term damage.
That shows up in studies looking at the impact of various drugs on our longevity. Whether we're talking proton pump inhibitors, we're talking benzodiazepines, we're talking about other sedative hypnotic drugs. We're talking about acetaminophen or Tylenol. Very simple drugs often produce disastrous long-term effects. So philosophically, I want to help people get away from that mentality and focus on what they can do to build health. To create a matrix in their body that will support them for the rest of their lives. What I found in most people, Mark, is that they're not so much interested in living longer. They want to live better and stronger now. One of the first things I focus on in the book is helping people create a why.
Because what I found, and you probably found this as well, many people really don't want to be here. They're not happy. They're dealing with health issues that are hard, and they're struggling. Life is such a challenge, and they don't feel well. Talking to them about living more like this, it's not appealing to them. So helping them realize that's not what life is supposed to be. Life is a celebration. We're supposed to be getting up every day and say, "Fantastic. Man, I'm thankful to be alive today. This is what I'm going to do." And go out and do it. There's a lot of things that go into feeling like that. That's really the basis of my book, and I'm sure your book as well. We have to help people feel better now, so they want to live longer.

Dr. Mark Hyman:
That's absolutely true. In terms of the protein question, I want to come back to that. I think in the longevity field there's a lot of debate about this. A lot of longevity researchers are suggesting we should be vegan, because we don't want to stimulate mTOR. Can you kind of speak to that, and the whole idea of protein and aging and muscle mass, and the balance between sarcopenia and the need to build muscle, but also the need to do cleanup and repair through autophagy, which is cellular cleanup?

Dr. Michael Murray:
Yeah, it's a big topic. I eat predominantly a high protein diet, but I try to get my protein from clean sources. I rely on whey protein. I know that's controversial for some people, but it's a very high quality protein and it's very clean. I focus on a moderate consumption of fish, particularly clean fish like salmon. I also focus on eggs and egg whites. That's where I get the majority of my protein. I like a high protein diet, because I think that promotes muscular health. If you don't have that protein intake, then you're going to lose muscle mass. When you lose muscle mass, you're accelerating aging. Muscles are the main furnace of our body. It burns fat, it helps our metabolism. Everything works better if we have an appropriate muscle mass.
When we start losing that muscle mass, and as we age we're gradually losing it, then we start being more frail. We now know that sarcopenia, the loss of muscle mass, is kind of the predecessor to osteoporosis. We know that there's a link between sarcopenia and loss of cognition. We're starting to understand that it's important to build and maintain our muscle mass throughout our life. That plays into the next area, lifestyle. I'm a big believer in regular exercise. It's a great investment. For every hour of exercise you put in, you're supposed to live two hours longer. You and I, we should never die with all the exercise that we find in our life.

Dr. Mark Hyman:
That sounds good to me.

Dr. Michael Murray:
Exercise is one of the best correlators to living a long life. I think certain exercises are more effective at doing that. Sure, we've got to get our heart rate up, but we also have to build muscle mass. I think that's important for our health and for living longer. I'm a big proponent of strength training. I'm a big proponent of stretching and getting body work done, making sure you're structurally aligned. I remember once this woman came up to me after a lecture. She was all hunched over, and her posture was really bad. She says, "Hey, I've been taking glucosamine, and I haven't really seen any benefit." I said, "Well, we've got to straighten out your mechanics here. Because you have mechanical stress, and nutrition can only do so much there. We've got to get you aligned better, and get your biomechanics better." I'm a big proponent of really taking care of your body in every aspect. Feeding it right, making sure it's getting exercise, and making sure it's in proper alignment.

Dr. Mark Hyman:
Yeah. The musculoskeletal health is super important, because that's what determines our function as we get older, and we often lose that. That's a really key, key part. I want to dive now into a sticky area that I love, but you also clearly love, which is the area of supplementation. The argument goes, why do we need supplements? Why can't we get everything we need from whole foods? If we eat a whole foods diet, our hunter-gatherer ancestors never had supplements. Why do we need them? First answer that. Then let's dive into actually what we do need, and why we need it, particularly in the perspective of longevity research.

Dr. Michael Murray:
Yeah. Our food supply has changed more significantly than our DNA and what our body requires. Our food supply today has no resemblance to the food supply that we had thousands of years ago. Even the paleo diet is kind of a joke, when you start looking at what they ate back in the Stone Age. They didn't have-

Dr. Mark Hyman:
They weren't having paleo chocolate chips, right?

Dr. Michael Murray:
No, no. It was much different than what we have available now. The question is, I think, can we provide the optimal level of not only the nutrients our body needs, but also the phytochemicals from diet alone? The simple answer is no. It's impossible, because our food supply has changed so much. It's no longer nutrient rich. It's no longer phytochemical rich. The type of phytochemicals in our food has changed, and it's changed by modern farming. I'm sure you've had many experts talk about this. If we look at the flavonoids, as I said, I loved them.
If you look at the flavonoid composition of organically grown tomatoes and compare it to GMO tomatoes, it's different. The pesticides, herbicides influence the plants' production of these, like you mentioned, protective compounds. I really think that it's important to take advantage of all these super foods that we have available to us, and all these supplements that can help promote health and longevity. If we don't, yeah, we might be able to get by, but we're not going to be thriving. I'd rather see people thriving than just getting by.

Dr. Mark Hyman:
I agree. In terms of longevity, what are the things that are the kind of have-tos? I mean there's a list a mile long. I want to talk about your personal recommendations that you take. I've looked at your list, and it's quite extensive.

Dr. Michael Murray:
Right.

Dr. Mark Hyman:
What are sort of the have-tos, the non-negotiables that are really key that are backed by science around what we need to take for longevity?

Dr. Michael Murray:
Yeah. I think in anything you're doing in life, sports, your job, building health, you have to pay attention to the foundation. So your question is, what are the foundational supplements that promote longevity? I think you need a good high potency multiple vitamin and mineral formula, because a deficiency of any single nutrient can have catastrophic effects on our health. Next, I do believe in the vitamin D3 research. I do think that it's critical that we have adequate vitamin D3 levels. So take enough vitamin D3 to get you in that ideal range, 60 to 80 micrograms per ml.
Then next, I think these pharmaceutical grade fish oils are a great gift. You're getting these long-chain omega-3 fatty acids in a very clean form. You have thousands of scientific studies showing the benefits of these long-chain omega-3 fatty acids to our health. Taking a good high quality fish oil, getting enough of them. Getting at least 1,000 milligrams combined with EPA and DHA each day, I think is a good goal.
Next, I think it's important to take some sort of plant-based broad spectrum antioxidant. A good flavonoid rich extract would be a good choice. Something like a grape seed extract or a pine bark extract, in the range of 150 to 300 milligrams per day. You could take one of these enhanced versions of curcumin. That would be a good choice. There's so many great broad spectrum antioxidants. You could take a greens drink, just something that's rich in phytochemicals that can produce some real benefit.

Dr. Mark Hyman:
I mean, it seems like the ones that you've actually listed in your personal list are the ones that seem to be, for me, the most data on health and longevity. Like quercetin, curcumin, green tea extracts, resveratrol, grape seed extract, which are the things that actually are based on literature the most promising.

Dr. Michael Murray:
Yeah. Yeah. Well quercetin is interesting, because it activates the longevity gene. Everyone's trying to... I know NMN is a big thing, but what you're doing is you're filling in a bucket that has a hole in it. There's an NMN bucket, but there's a hole in it. So we're filling that bucket up continually by taking NMN, instead of fixing that hole. That hole is related to an activity of an enzyme. We can help heal that bucket by taking quercetin. It activates that longevity gene, and that raises the body's own NAD+ levels, instead of having to take NMN. I think-

Dr. Mark Hyman:
What is that longevity gene you're talking about with quercetin? I think that's a very important one for longevity, that maybe people haven't heard of. It also seemed to be very effective in COVID and helping with the immune system. It's great for allergies and gut healing. Tell us a little bit more about the mechanism action of quercetin, because I think it's something people hear about but may not be aware of.

Dr. Michael Murray:
Yes. This particular gene increases the expression of the enzyme that regenerates NAD+. NAD+ levels tend to decline as we age. People are taking things like nicotinamide riboside or nicotinamide mononucleotide, NMN, to try and boost NAD+ levels. But quercetin and other flavonoids, by influencing the production of a very specific enzyme, can help regenerate that NAD+ in I think a more sustainable fashion. Otherwise, you're not addressing the underlying cause. Good medicine always involves trying to understand what's really going on in the cell and in the body, and trying to repair it.

Dr. Mark Hyman:
Do you remember the name of that enzyme?

Dr. Michael Murray:
It's naphthoquinone oxo Reductase one.

Dr. Mark Hyman:
Oh, that's a big one. That's a big one. Well, we're going to put that in the show notes. It's an interesting mechanism of action, and I think that's a very insightful point. Maybe even if you took NAD or NMN or NR, and you took quercetin along with it, it might help, right?

Dr. Michael Murray:
Yeah. Yeah. I personally don't take NMN, because I believe in the flavonoids that I'm taking.

Dr. Mark Hyman:
But you're also taking a lot of other stuff. You're taking things for detoxification and mitochondria, which play a big role in aging, things to help your metabolism. Can you talk about some of those compounds that you're taking?

Dr. Michael Murray:
Oh my God. Yeah. If you're looking at wanting to live longer, you've got to have plenty of energy. You have to ask the question, "Well, how do I make sure my energy producing machinery is working properly?" The best way to do that is to focus on things that help your mitochondria work better. Your mitochondria are the energy producing compartments of our cell. It needs virtually all the B vitamins. It needs co-enzyme Q10, and it needs protective agents around it. Basically your mitochondria are like a little mini nuclear reactor. They're producing energy, and that's what gives us life. In that process, it's generating a lot of pro-oxidants and oxidants that can cause damage to the mitochondria as well as our cell. There's some special compounds that protect the mitochondria. One of my favorites is called PQQ, that's short for pyrroloquinoline quinone. That's why we called it PQQ. I love this compound, Mark. I'm sure you've talked about it. It's found in stardust.

Dr. Mark Hyman:
Oh, wow.

Dr. Michael Murray:
You could make a claim that PQQ is the spark of life spread through the universe, because it's absolutely essential for life. It plays a key role in mitochondrial function. It's found in our diet in very small quantities, but they're necessary. It will someday be classified as a vitamin, similar in quantities to like folic acid. It is available in supplement form. It's been shown to work very well with coenzyme Q10. Yeah. Anyway, this-

Dr. Mark Hyman:
Is it related to CoQ10? It sounds like, from the name of it, it may be. Is it different than CoQ10?

Dr. Michael Murray:
It is. It's a bit different. We use this term antioxidant a lot, but there are as many different antioxidants as there are musical instruments, and you need that whole band playing. Every time an antioxidant performs its function, it's called the catalytic conversion. Some antioxidants are relatively cheap, like vitamin C. It can only be used four times and then it's spent. PQQ can survive 20,000 catalytic conversions. It makes it very special, and that's why it's really concentrated in the mitochondria, because it's a very valuable antioxidant to protect against damage during that energy production. Glutathione is another example of a key antioxidant. PQQ is many times more powerful than even glutathione. I don't know if anyone's talked about ergothioneine in-

Dr. Mark Hyman:
Yeah, no. We do. We have talked about it, but I'd love to hear your thoughts about it.

Dr. Michael Murray:
Yeah. Ergothioneine is an-

Dr. Mark Hyman:
Before you go on about PQQ, I just want to sort of say something about it. It's one of those compounds that activates what I call one of these longevity switches. Your body has these hallmarks of aging. The most important one of these is deregulated nutrient sensing. I call these four longevity switches that regulate insulin, mTOR. Sirtuins, which have to do with [inaudible 00:35:41] and things like that, NAD. But then there's AMPK, which a lot of people are taking metformin for. But PQQ activates AMPK, which helps to really work on all the longevity pathways.

Dr. Michael Murray:
Very well said. That leads us to berberine. Berberine is one of my standard supplements. It's a compound found in goldenseal. It has great research showing an ability to lower cholesterol levels, lower blood pressure, and lower blood glucose levels. If it was a drug, it'd be the biggest selling drug of all time. We're talking nearly 30 double-blind placebo controlled studies showing that this compound that's found in plants like goldenseal and barberry and gold thread can lower cholesterol levels as well as a statin, can lower blood pressure as well as an ACE inhibitor, and can lower blood sugar levels as well as metformin.

Dr. Mark Hyman:
That's impressive.

Dr. Michael Murray:
It has some other really unique effects as well, including activation of AMPK. Yes, there's a lot of compounds in nature that activate AMPK, and my whole diet is full of them. It's just amazing all these different compounds, they all have some common features. Nerve 2 activation is another key anti-aging strategy. It's a non-specific call to arms by our cells to activate our antioxidant mechanisms. One of the things that has happened in flavonoid research and some of the phytochemical research, they do test tube studies to see what actions it might produce. Those test tube studies show us what the concentration is that's required to produce those effects. Sometimes it's not possible to achieve that level of concentration. They get metabolized, they get bound to the compounds.

Dr. Mark Hyman:
Inside the cell, right.

Dr. Michael Murray:
But they're still active, so how are they working? That turns into a really interesting study. We see more clearly, as pharmacology has evolved we've rediscovered some of these compounds that we thought weren't active, because we didn't have the models to explain how they work. What we're seeing is that many of these natural compounds activate really important cellular targets. Like you mentioned the four hallmarks of aging in. Cyclic AMP is certainly one of those key factors. It not only lowers lipid levels, improves blood sugar levels, it increases the formation of mitochondria. You increase the number of mitochondria, you increase the energy of a cell. You increase the energy of the cell, it works better.
I look at it, the brain is our most metabolically active tissue. Yet many people, their dimmer switch is turned to dim, because they don't have the mitochondrial energy production needed to have that brain be bright and to function properly. It's an epidemic of mild cognitive impairment to dementia in our elderly right now. I think helping them have more mitochondrial numbers and better mitochondrial function is the solution. Many of the things that we look to, to improve mitochondrial function, improve brain function as well.
I started taking this product, Mark. It's from our friends at Natural Factors. It's called RegenerLife. I love this product. I take a lot of pills, but this comes in a powdered form. You've got a little scoop here, and you just empty that orange powder into your glass and you've got a great cocktail. It contains acetyl-L-carnitine, CoQ10, and some other key compounds for enhanced mitochondrial function. It's just a great way to get that dimmer switch to turn up a bit.

Dr. Mark Hyman:
Yeah. I put that in my smoothie every morning. I do actually. It's great.

Dr. Michael Murray:
Yeah, yeah.

Dr. Mark Hyman:
I think it's just important to emphasize what you said earlier about these plant compounds that work on these pathways that drugs work on. A lot of people in the longevity field are thinking about metformin, and taking this diabetes drug for longevity. There's a large trial going on now called the TAME trial, Targeting Aging with Metformin, which is really designed to determine whether or not this is an effective longevity intervention that can reverse biological age. But what you're saying is that there are many of these compounds like berberine and other things that actually do the same or work better than these drugs. Is that true?

Dr. Michael Murray:
Yeah. Yes, absolutely. The contrast between berberine and metformin is really interesting. Metformin, by the way, was originally isolated from a plant. Conceptually it is a natural product, and it does have a place in medicine, but I think that berberine might be a better choice. What's interesting about both metformin and berberine is the effect to the microbiome. I'm sure you've had patients that-

Dr. Mark Hyman:
In different ways, though.

Dr. Michael Murray:
Yeah, exactly. I'm sure you've had people on metformin. What's their biggest complaint, Mark?

Dr. Mark Hyman:
Digestive problems. Digestive problems, yeah.

Dr. Michael Murray:
Yes, yes. Because I don't think it's affecting the microbiome in a healthy way. Berberine has phenomenal effects on the microbiome. It's a selective antibiotic. It's a pathogen specific, disease-causing organism specific antibiotic, and it promotes the growth of many health promoting bacteria. One of the key ones is called akkermansia eosinophilia. This bacteria, it works with our intestinal cells to create the mucin layer. It's given the name eosinophilia. Philia means love. It loves that mucin, and it helps improve the quality and function of that mucin. When we talk about leaky gut, we're talking about the loss of that mucin, and we're talking about a deficiency of akkermansia eosinophilia.
When we talk about diabetes, when we talk about non-alcoholic fatty liver disease, when we talk about systemic inflammation caused by a leaky gut, we're talking about decreased akkermansia eosinophilia. Berberine increases the counts of this health promoting bacteria. It helps reestablish that mucin layer, and is a very important remedy for leaky gut, diabetes and systemic inflammation, fatty liver disease. All these sequelae of what we know are the result of absorbing gut-derived toxins that create all these problems in our liver and our metabolism. I think the contrast between metformin and berberine on gut health, it's night and day. One, metformin, questionable benefits, maybe some harm. Berberine looks very beneficial.

Dr. Mark Hyman:
Interesting. Maybe we're searching for love in the wrong places. Maybe the plant kingdom actually is a source of a lot of these compounds. This is what I found when I wrote my book Young Forever. A lot of these compounds are in nature working on these pathways that we are trying to find drugs for. But they do it in a way that's kind of more in line with nature, less likely to have side effects, and potentially even more benefit.

Dr. Michael Murray:
Yeah. What's exciting, Mark, is the best from nature is yet to come. I've had my fingers on the pulse of research for over 40 years now. I'm telling you, with the increase in our understanding of how natural compounds work in our body, we're going to be gaining a greater appreciation. One of the biggest indicators of how far we've come in that regard is looking at curcumin. Curcumin's been the subject of over 8,000 scientific investigations. Why are researchers studying curcumin? Because they're trying to find a drug that'll produce the same actions, and they haven't been able to find one. There's been intense research over 20 years.
Most natural compounds exert what are called pleiotropic effects. This is unknown with traditional drugs. If we look at inflammation, like a Celebrex or an aspirin, they work on one enzyme. There are over 40 different enzymes that have been implicated in causing the cascade of events that lead to severe inflammation. Curcumin impacts all of them. It's been shown to impact every known activator of inflammation, while the drugs only work on one or two. It's really quite interesting. I believe in the power of nature. We fall in love with technology.
I wrote a book called The Magic of Food. How I came up with that title was that Sir Arthur Clark, who wrote 2001: A Space Odyssey, had a great quote. He said, "Any sufficiently advanced technology is indistinguishable from magic." We have lost sight of where true technology lies. We're all amazed by our iPhone and our computers and all this technology, but the greatest technology in the universe is nature. The way we commune with nature on a daily basis is through the food that we eat. You've talked about this for years. I listened to a lecture where you said, "Food is information." It's information, it's technology, and it's beautiful.

Dr. Mark Hyman:
Yes. Right. It's really like... Yeah, it's true. Technology is about information. Food is information, and your biology is an informational system. Actually there's a whole new theory of aging called the information theory of aging, which talks about the dysfunctional information that we're either producing or that's being put in our biology, that's actually causing us to age rapidly. It's exactly this problem.

Dr. Michael Murray:
Oh, wow.

Dr. Mark Hyman:
Michael, I wanted to sort of loop back on this ergothioneine thing. We went down the rabbit hole of berberine and some of the other compounds, PQQ, but I want to sort of talk about this. It's something people may not have heard about, and it's an interesting new compound that we've found plays a role perhaps in aging.

Dr. Michael Murray:
Absolutely. Ergothioneine is an amino acid that has a sulfur molecule. It's part of a group of compounds called thiol, kind of like co-enzyme Q10 and glutathione. The richest dietary source is mushrooms. When you start looking at the data... We talk about the Mediterranean diet. We look at these people living in Japan that live long. You could make a very strong case that the intake of mushrooms is the most significant factor associated with these folks living longer and being healthier, because mushrooms are rich in this compound ergothioneine.
It'll be considered a vitamin someday. The reason why it's not now is that it has existed in our food supply in low quantities for forever, but our food supply is different. For example, this ergothioneine is produced by fungi. The ground, which contains a lot of fungi, if it's being tilled excessively, or you're dumping a lot of pesticides and herbicides into that soil, the fungal content is decreased. With decreased fungal content, we get reduced ergothioneine content. Ergothioneine, I talked about-

Dr. Mark Hyman:
In all plants, or just in mushrooms?

Dr. Michael Murray:
In all plants. It's found in all foods, even animal foods in small quantities. Historically we've been getting our ergothioneine bucket filled, but now we're only getting it filled through eating mushrooms. A higher diet composition of mushrooms has higher ergothioneine levels. A lot of the benefits that we know with mushrooms, like preventing cognitive decline and promoting anti-aging effects, it's related to their ergothioneine content. To me, looking at the data, it just really signifies again how far we've come from what we're designed to be consuming. This is a compound that I think historically humans were getting plenty of, because they were eating dirty food.

Dr. Mark Hyman:
What does it do? What's the mechanism of action? How does it influence us? How does it-

Dr. Michael Murray:
Yeah. It's a very powerful antioxidant, so it exerts anti-inflammatory effects. Those are kind of blanket terms. We can look at specifically the way that it works. You think of it, glutathione is a tripeptide, so it's a very large molecule. This is a very small molecule. It's just one amino acid. We actually have receptor sites on our cells that pump it into the cell. Our cells only have those receptor sites for things that are really important, like potassium and magnesium.

Dr. Mark Hyman:
Yeah, yeah. Interesting.

Dr. Michael Murray:
It's very important. What it does inside that cell is it acts as one of the primary antioxidants, and it's very important in preventing cellular damage. We know that oxidative damage is what is associated with aging. Bruce Ames, who developed the Ames test looking at mutations, he identified ergothioneine as one of his longevity vitamins. It will be considered a vitamin like PQQ, like quinine and like a few other compounds that are absolutely essential. They haven't been a big deal, because we were getting the trace amounts that we need from the foods that we eat. But now our farming techniques have changed. The composition of our fruits and vegetables and other foods has changed. And we've got this ever-increasing load of pesticides, herbicides and other manmade chemicals. Yeah. We really need these compounds that are cellular protectors, and ergothioneine is one of the key cellular protectors.

Dr. Mark Hyman:
Yeah, interesting. It's interesting. When I went to Ikaria and the Blue Zones, they ate a lot of mushrooms, and they ate a lot of wild mushrooms. It was just sort of part of their diet. They were always foraging and hunting for mushrooms. Are there particular mushrooms that have higher levels that people can buy at the grocery store, or is it just sort of like-

Dr. Michael Murray:
Yeah, even button mushrooms will have it. Cremini mushrooms, the darker brown ones, they're often sold as buttons, they're higher. Shiitake, lion's mane and oyster mushrooms have the highest levels, but you'll find it in all levels.

Dr. Mark Hyman:
Well I love shiitake mushrooms. I roast them. I stir fry them in a little olive oil and garlic. It's great. They're good.

Dr. Michael Murray:
Yeah. If we look at the per capita estimated ergothioneine intake in America, I might not get these numbers exactly right, but I think it's like six milligrams. We compare it to Italy, it's like 13. It's almost two and a half times. It's about 13 milligrams.

Dr. Mark Hyman:
Oh, wow. Really?

Dr. Michael Murray:
Yeah. If you think about it, think about all these Blue Zone cuisines. Mushrooms are usually part of the diet.

Dr. Mark Hyman:
Yeah, it's true. They really are. I found that when I was traveling in the Sardinia area. I was like, wow. They always were serving them. I'm like, this makes sense. It's just what we ate. It's one of those foods that are forageable, so probably we've been eating it for hundreds of thousands of years, if they didn't kill us. Are there any other kind of up and coming compounds that you're excited about, that we may not have heard about? Ergothioneine, is that something you can take as a supplement, or you just have to eat mushrooms?

Dr. Michael Murray:
Yeah. It is available as a supplement. I think 25 milligrams is a good amount. There's so many compounds, Mark. As I told you, I have an affinity for flavonoids. One flavonoid is quite interesting, nobiletin. I don't know if you've heard of nobiletin. It's a flavonoid that was originally isolated from unripe tangerine peels. What's interesting about it is it opened my eyes up to the fact that all cells of our body have a circadian clock, a biological clock. They screened over 5,700 compounds, looking for compounds that will bind to these receptor sites that regulate each cell's biological clock.
This nobiletin was able to bind and influence that, improve resonance of the cell. This is really interesting, because it has a chemical effect, but it produces a frequency effect. It causes increased cellular oscillations, and it has remarkable benefits at reasonable dose levels. It's one of the few flavonoids that is bioavailable without being transformed and conjugated. I think that's one that's really exciting. I mean there's so many others. I think spermidine is an interesting one.

Dr. Mark Hyman:
Oh, that sounds like an interesting one. Tell us about spermidine.

Dr. Michael Murray:
Yeah. Spermidine aine is part of the putrescine family, polyamine family. Historically these have been associated with kind of poor health, because some of them don't sound too good, like cadaverine and putrescine.

Dr. Mark Hyman:
Yeah, no, exactly.

Dr. Michael Murray:
Spermidine actually has a lot of anti-aging effects. When we lose spermidine content in our cells, we lose a very valuable component to regulate cellular function. We start seeing accelerated aging in cells that have a lower spermidine content, and there's disruption of this whole polyamine pathway. I think spermidine is quite interesting. Wheat germ is one of the richest sources. There's some good research coming out with wheat germ extract for spermidine supplementation.

Dr. Mark Hyman:
What's the mechanism of action of spermidine? How does it sort of enhance longevity?

Dr. Michael Murray:
Basically, it's a polyamine, so it's donating those amine groups when needed. That helps with stability of the epigenetic matrix, like histones. With greater stability of that DNA, you get better transcription.

Dr. Mark Hyman:
Amazing. Amazing. Well, this is just such great information, and I think we've covered a lot of ground. I think we've gone deep into the world of supplements, which is interesting for people. I think people can get overwhelmed and take too much stuff. I think you're ambitious. I think I tend to be more in your camp, but I mean it is still experimental. When you throw all this stuff in your body, what happens? How much of it's used? How much of it's wasted? What is actually it doing? How do you track the results? I mean there's all these questions, but I think there is really good evidence for some basic foundational things that you mentioned, and that we'll link to in the show notes. Any final thoughts or words for people who are focused on, what are the key strategies for living a longer and healthier life?

Dr. Michael Murray:
Oh, boy. Like I said-

Dr. Mark Hyman:
What do you do, Michael?

Dr. Michael Murray:
I do it all. I do it all. I try to have good thoughts. I try to have a good attitude. I try to have a very healthy lifestyle. Getting enough sleep, Mark, that is really key to life in many ways. If you sleep well, you have more energy. If you have more energy, life is easier. Everything's brighter. One of the biggest tools I've found to help people feel better is to help them get a better night's sleep. I really believe in the power of a good night's sleep. It just recharges us. It cleans our cells. It recharges our batteries. Then exercise. I believe in that.
Then I eat a very clean diet, and I focus on giving my body all the tools it needs to be as healthy as possible. I eat the good things. I stay away from the bad things. Yeah, I'm a health nut, which is crazy. Right? We call people nuts because they're wanting to live the healthiest version of themselves in life. It's crazy in my mind not to be that way. I encourage people to embrace being a health nut, and do everything that they can to make those choices they make every day healthier choices than they're currently making.

Dr. Mark Hyman:
It's just that simple really, isn't it? It's just sort of incrementally adding those things in that we know support our health. As we get older, we need to do more of them. I really thank you for your lifetime of work and service in advancing natural medicine, and providing a lot of the insights and understandings that I first got 30 years ago, as I began to look at this field. The Textbook of Natural Medicine was such a key part of that. I encourage everybody to check it out. Check out Michael's book, The Longevity Matrix, which is out now. You can check out his website, DoctorMurray. That's D-O-C-T-O-R Murray.com. You will not be disappointed when you dive into his great body of work. Michael, thank you so much for all your contributions to advancing the field of natural and functional medicine.

Dr. Michael Murray:
Well, I love you, Mark. It was great fun, and I look forward to connecting to you in person at a near future time.

Dr. Mark Hyman:
Yeah. Hopefully maybe you'll be at the Integrated Health Symposium, so we'll see you there.

Dr. Michael Murray:
Okay.

Dr. Mark Hyman:
Great to see you, buddy, and good luck with everything. If you loved this podcast, everybody listening to us, share with your friends and family. I bet they'd love to hear about it. Leave a comment. What's worked for you? How have you felt better? What have you found works best for optimizing your energy, and maybe helping you live longer? We'd love to hear. We'll see you next time on The Doctor's Farmacy.

Closing:
Hi, everyone. I hope you enjoyed this week's episode. Just a reminder that this podcast is for educational purposes only. This podcast is not a substitute for professional care by a doctor or other qualified medical professional. This podcast is provided on the understanding that it does not constitute medical or other professional advice or services. If you're looking for help in your journey, seek out a qualified medical practitioner. If you're looking for a functional medicine practitioner, you can visit ifm.org, and search their Find a Practitioner database. It's important that you have someone in your corner who's trained, who's a licensed healthcare practitioner, and can help you make changes, especially when it comes to your health.