I am delighted to have Shawn Wells, affectionately known as the Ingredientologist, joining me again today. Shawn is a leading nutritional biochemist and health optimization expert. He is also a biohacker and the formulator of over 500 supplements, foods, beverages, and cosmeceuticals.
In our conversation today, we cover how to evaluate the quality of supplements, explain what proprietary blends represent, and explore several exciting new supplements like Peptide 185, Paraxanthine, and various nootropic agents. Shawn shares his optimal supplement stacks for sleep, metabolism, gut health, and regulating blood sugar, diving into the impact of delivery systems, including transdermal approaches and IV therapies. He also offers guidance on setting intentions and affirmations around supplement consumption.
I trust that you will find this conversation with Shawn Wells as enjoyable and informative as I did while recording it.
IN THIS EPISODE YOU WILL LEARN:
Shawn shares his concerns about quality control in supplement manufacturing.
Why it is essential to buy supplements only from trusted brands when ordering from big retailers
Shawn discusses the potential benefits of the new supplement, Peptide 185, for muscle protein synthesis.
The potential leucine holds for age-related muscle loss and sports nutrition.
Shawn dives into the physical effects of the caffeine metabolite paraxanthine.
BDNF-boosting ingredients for neuroplasticity and brain protection
How adaptogenic herbs can increase resilience and improve sleep quality, energy, and focus
Shawn highlights the importance of physical movement and proper posture for maintaining physical health.
How a leaky gut can lead to immunological problems and cognitive impairment
Shawn explores the effectiveness of supplementation versus methods like high-intensity interval training for boosting NAD levels.
Shawn explains how to use intention and affirmations to maximize the absorption of supplements.
Bio:
Shawn Wells MPH, LDN, RD, CISSN, FISSN is the world’s leading nutritional biochemist and expert on health optimization.
Meet the Ingredientologist, a visionary scientist behind over 1000 groundbreaking formulations, including 25 patented ingredients like Paraxanthine, Teacrine, Dynamine, and Dihydroberberine. Once a Chief Clinical Dietitian, he has empowered thousands with innovative health solutions like keto, paleo, fasting, and supplements, overcoming his own battles with Epstein-Barr Virus, Chronic Fatigue Syndrome, and more.
As a world-renowned thought leader on mitochondrial health, he has spoken on five continents and featured in acclaimed documentaries and podcasts. Discover his practical, research-backed solutions in "The ENERGY Formula," hailed by USA Today, Forbes, and an Amazon best-seller. Experience greater resilience and boundless energy under his expert guidance.
“It is very important that there is full disclosure and
full transparency with proprietary blends.”
-Shawn Wells
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Connect with Shawn Wells
Cynthia Thurlow: [00:00:02] Welcome to Everyday Wellness podcast. I'm your host, Nurse Practitioner Cynthia Thurlow. This podcast is designed to educate, empower, and inspire you to achieve your health and wellness goals. My goal and intent is to provide you with the best content and conversations from leaders in the health and wellness industry each week and impact over a million lives.
[00:00:29] Today, I was joined again by Shawn Wells. He's a leading nutritional biochemist and expert on health optimization. He is also a biohacker and has formulated well over 500 supplements, food beverages, and cosmeceuticals. He is affectionately known as the ingredientologist, the scientist of ingredients. Today, we dove into how to evaluate the quality of supplements, what proprietary blends really represent, several new exciting supplements including peptide 185, paraxanthine, and nootropic agents. His favorite stacks for sleep, metabolism, gut health, and blood sugar dysregulation. How delivery systems impact our ability to absorb supplements, including transdermal approaches, IV therapies, and more, and intentions and affirmations around supplement consumption. I know you will enjoy this conversation as much as I did recording it.
[00:01:33] Shawn, welcome back to the podcast. So good to reconnect with you.
Shawn Wells: [00:01:37] It's amazing to be here, Cynthia. I love being on. I'm so happy to have a conversation with you and your community. It's great.
Cynthia Thurlow: [00:01:46] Yeah. A lot of the questions that came in for our conversation were centering around how do we source high quality supplements? And this may seem kind of basic, but I think it’s important. Like as an example, I don’t recommend people buy supplements at like Costco, because generally you’re not going to get what you’re paying for, but obviously I know you have a higher-level perspective because you’re so intimately involved in helping companies create supplements and looking at companies from the inside out. So, help the listeners understand how to navigate purchasing high quality supplements. What are the things they need to be looking for? What do they want to avoid?
Shawn Wells: [00:02:26] It's kind of scary. I'm going to try and remember these numbers right now, but I want to say these are about it, so don't hold me to the exact numbers. But NOW Foods, who's been in the industry for 40 years probably, and a really trusted company, actually have a bottle right here. So, we'll talk about tyrosine, maybe.
Cynthia Thurlow: [00:02:45] Sure.
Shawn Wells: [00:02:46] I don't know if this is video that's going out, but anyway, NOW Foods, the orange and white label which is near and dear to me because that's my branding formula.
[laughter]
[00:02:57] But anyway, a phenomenal brand and obviously they were kind of the best quality for the value for a long time. And then Amazon came in and just destroyed the whole market, upended everything. But they've been doing testing on a number of ingredients and they published these tests. They sent all these different things from Amazon, from Walmart out for testing. They've looked at a few different ingredients. One that I can remember is astaxanthin. And almost every time it's come up like this. So astaxanthin, I want to say they tested like 44 different products and they found 33 did not meet label claim and 21 of those. so about half did not even have 1 mg of the claimed amount. So, this is a huge problem. And I don't mean to discourage anyone listening that like, “Oh, no. Like this is, you know, this major freakout moment that no supplements work. I've always been scammed.” Part of the problem is on Amazon, they're not doing quality control testing, they're not demanding those tests. It has shifted since some of these results have been published.
[00:04:15] But that's the concern, is that these products are not testing out and they're driven to just sell as cheaply as possible on Amazon. So, the incentive really isn't there to have the highest quality control. And there are companies that may be just buying the cheapest thing from China and not doing their own testing, so it may not be 100% their fault. Some are doing the testing and know exactly what they're buying and are being deceptive. So, where does this leave us? One, you can buy from quality companies that have been around a long time, like Designs for Health, Life Extension Foundation, NOW Foods, Jarrow, Nordic Naturals, Thorne, Pure Encapsulations like these are really good brands that have been around for 30 years and everyone knows them. They have stood the test of time. They have quality control. So those are ones that you can trust.
[00:05:15] And if you're going to go on Amazon, then I would make sure that you're getting a first party product from those sellers. If it's a Thorne product buying from the Thorne store on Amazon, or if you're going to get it from a third-party seller, it's a reputable one, like GNC vitamin shop, whatever, something along those lines on Amazon. If it's Joe's Crab Shack selling [Cynthia laughs] whatever product on Amazon, there's a good chance that these could be counterfeited. So that's one concern, that even your Thorne product could be counterfeited, and they've found that quite a bit. But two, if you're just buying any version of whatever you're looking for, L-Tyrosine, acetyl L-carnitine, whatever it is and just buying whatever's cheapest, there's a good chance that's not testing out either. There's about a 50% chance that that's not testing out. So, this is where reviews can be manipulated as we know. So, these are some things to look at is go for quality brands, go for good sellers like either first party or the third party that you know and trust a Vitamin Shoppe or GNC or what have you. So those are some things to look for.
[00:06:32] Now that doesn't mean that a new company isn't necessarily a good company because I formulate for a lot of new companies and I definitely don't cut corners. So one thing that you can do is hopefully look at some good reviews. I actually like to look at the three star reviews. Those are actually the legitimate reviews. Psychologically there's a lot of bombastic, hyperbolic or fake reviews that are ones and fives. And then also there are some companies that do some testing of these sellers of these brands like labdoor.com you can go to, there's some different sites like that. Consumer Reports still has some stuff that they put out, but you can also as a consumer reach out to these companies, call that number on the back of the bottle and say, “I'd like to see your third-party quality control test and I'd like to see a test done on this lot.” And if they say we don't have that, we don't know what you're talking about. That's a good sign that they're just crap. So, there are great companies out there. Certainly, if you reach out to me, if you DM me I can tell you what's good, what's not. But that's an easy way is to just go with trusted brands that have been around. And certainly, the stuff that's only on Amazon that's brand new, that maybe doesn't have a lot of reviews. That's where I'd start definitely questioning its validity.
Cynthia Thurlow: [00:07:53] Yeah. I think that’s really helpful because as an example, I think it was either an Apex product or a Biotic’s product. And a client came to me and I made some recommendations and she went to Amazon and she called me up and she said, “Well I know that this Biotic’s product should have this many capsules in the container but its twice as large.” And I said, “Well, why don’t you call Biotics?” And sure, enough Biotics was “That’s not a-- we don't third party source. So, we wouldn't allow Amazon to sell our products.” And so I always say, “Let the buyer beware.” That's not to suggest, as Shawn said, there's lots of good companies out there. I like to use Fullscript to actually source supplements.
Shawn Wells: [00:08:36] Yeah.
Cynthia Thurlow: [00:08:36] And they're one of those companies that's an in between. And they're actually quite strict, companies like OrthoMolecular Apex. I have to have an actual account with them. I cannot go to Fullscript and place an order for myself. I could do it for a client or a patient, but if I want to order for myself, I have to go directly to the company themselves. They keep a very tight control over where their stock is sold and who it's sold to. So, that's definitely really helpful because I think for a lot of people, they assume if they go to Walmart or Costco, that they're going to get exactly what's identified on the exterior of the label. And more often than not, as you mentioned, those studies that are done or those research efforts that are done, more often than not, they find out it's exactly the opposite. It could be all filler and not actual product.
Shawn Wells: [00:09:24] So some other scary things, [chuckles] not to freak everyone out, is that we're just talking about getting what you paid for, but sometimes you're getting other things that you don't want in there. And that's the flip side of this equation, is when there's not really good quality control, they could be sourcing something very cheap. They could be working with an inferior contract manufacturer where you may be getting heavy metals in there, you may be getting something that doesn't test out at that level, that may be, for example, this is a vitamin D, K2. This has happened in the past where the vitamin D3 level was 100 times the level it was supposed to be, whoops. They found this with melatonin too where a lot of times, when these ingredients are very small doses, sometimes there's wild variation in that blending process when you're not working with a really good contract manufacturer and you get what's called hot and cold spots in the blend.
[00:10:24] So, when it's in that blender, if they don't blend it properly and you have very tiny doses, you could have a spot where if you make something from that part of the blend, it could be a hundred times. And then you make something from this part of the blend and it's 1000th, so it can be these hot and cold pockets if they're not doing the proper work. This is where, when I've formulated supplements, we do many blends. We do scale ups, and then we test at the beginning, middle, and end, and then we work on the blending process and how to get it right. And there's a lot of work to be done there. So, that's something to be concerned about. And then if you get these products that have 500% more blah, blah, blah or 9000% more muscle, that's usually a concern. Another thing to look for is what I would call full disclosure. I'm looking for something like, here's a product that has my ingredient, paraxanthine that we'll talk about. This is full disclosure. Every single ingredient has the dose, has the genus and species, has what it's standardized to. Everything is clear. There's no proprietary blends.
[00:11:42] So that's a massive, massive point of importance, is I do not like proprietary blends. I want to see everything listed, the daily value. If it's a nutrient, I want to see the dose, I want to see the form. I want to see the genus and species. I want to see what the herb is standardized to. For example, if it's ginseng, ginseng leaf may not do a whole lot. Ginseng, whole plant may not do it, ginseng root. Okay, that's where most of the benefit is. And then up one more level is to see standardized for ginsenoside A. Okay, cool, like 5%. And then we know exactly what we're getting at this exact dose. And then paired up with the right frequency, meaning number of times per day. Now we can go look at the study and see, “Okay, now, this aligns with the study.” In this study, they gave 200 mg of ginseng root standardized for 5% ginsenoside A three times a day. And they saw these results, and that's why this company is formulating this way.
[00:12:48] And so, if you're formulating the correct way and you're doing all these things, it's a lot more cost intensive to source the best versions of these ingredients, because you're held to that standard. Instead of just me sourcing, just raw ginseng powder of whole plant, which might be $5 a kilo, if I get something that's standardized, it could be $500 a kilo. So as a formulator, is the temptation there to just put in fluff that just has the name that most people don't understand or delineate the difference from? Sure. But that's never the way I'm going to work. But there's definitely plenty of people that do. So this is where you know, yes, like some of these brands like Thorne and all these companies like that, all the products listed on Fullscript, like you mentioned, I love that store as well. They've been tested and they're going to not just test out, but potentially work the way you expect it to work and not have the other things in it that could potentially be dangerous, harmful, etc. So, yeah.
Cynthia Thurlow: [00:14:02] The proprietary blends is the concern. Obviously, it's the integrity of the company. But I initially understood that terminology to protect intellectual property. You're shaking your head, so you're saying, “No, that's actually not the case.” So proprietary blends don't really give us a sense of what's in it. And certainly, for those of us that are sensitive to certain things, the proprietary blend may not disclose what actually is in the supplement itself. And that in and of itself can be problematic.
Shawn Wells: [00:14:33] So here's the thing, maybe in one in a hundred cases, that is actually the truth, but people that are lying and disreputable have always used that as a crutch and it's not a thing. The best brands do full disclosure, period. Now, if you were to legitimately do a proprietary blend, then you would do a study on your whole product or on your proprietary blend that can go into a product. Okay, cool. Then that's solved. But I guarantee when you ask them, “Okay, if it's intellectual property and you have a proprietary blend and you have your study on your couple ingredients or your whole formula. Oh, no, you don't. Okay, well, then you're just lying.”
Cynthia Thurlow: [00:15:16] Right.
Shawn Wells: [00:15:16] So that's clear. Now, it's very important that there's full disclosure, that there's full transparency. That's the only way that this should happen in my mind. I'm very frustrated at the amount of proprietary blends in the industry. And for example, like to break this down, I wish I had one in front of me. I just did a Mindvalley Quest on how to understand supplements that'll be coming out fairly soon. And I actually broke down a whole label and we have it on the screen and the whole thing, but I'll just make one up in my head. Let's say it's called the muscle boosting blend and it's got 17 ingredients and it's got everything that you've ever heard of. So, this way we can hit on the entire zeitgeist of any ingredient that you've ever heard of for muscle that's in this blend. And this blend is 1700 mg. Whatever is listed first could be 1699 mg. And all the other 16 ingredients could be 1 mg. So you'll see all these other ingredients, like, “Oh, wow, this is a good one. This is an expensive one.” It could be 1 mg and the first ingredient could be a great ingredient, but a cheap ingredient, like caffeine, like creatine, like betaine, or something like great ingredients, efficacious. But it could be the entire blend, essentially. And it's the cheapest one.
[00:16:41] Creatine is less than $10 a kilo on raw material side, whereas some of these other ingredients could be $2,000 a kilo. So, this is the game they're playing. And then quality control testing wise, they don't have to do one-tenth the amount of testing, as when you have full transparency. So, this is where it costs more to do the right thing. And I just hope people appreciate that. Please pay more for your supplements, use less supplements, choose wisely, pay more, get a good product. And then you can tell your friends, “Yes, supplements work.” And don't tell everyone that supplements don't work because you're buying supplements that, in fact, don't work. But that's not the case for all supplements. There's a number of us that are doing the right thing out there.
Cynthia Thurlow: [00:17:31] No, that's really helpful. And that's one of many reasons why I wanted to bring you back on the podcast today. You had mentioned to me in our conversations last weekend about some new supplements, new things that are on the market. Let's talk about Peptide-185. I think this is really exciting, largely because my listener base are very savvy. They understand what muscle protein synthesis is. They understand leucine threshold. So, let's talk about this peptide.
Shawn Wells: [00:18:00] Okay, that's awesome. This is really the only kind-- just hit the market, went exclusive with MuscleTech, kind of like, I did my paraxanthine ingredient prior. So, they have a window on this. But there'll be other companies coming soon. This is the product that's called Peptide-185 from them, but DL185 is the ingredient and it's dileucine, which is L-Leucyl-L-Leucine Monohydrate. So dileucine means it's two leucine’s together. Leucine is the key amino acid and muscle protein synthesis. So that was the gold standard for muscle protein synthesis. About 10 years ago, I started doing research on peptides and found that there's a unique transporter system in the gut called the PepT1 transporter. And this transporter takes up di and tripeptides uniquely. So, we always thought that single amino acids would be the fastest. It's broken down the most, it should be the fastest in getting to plasma to blood.
[00:19:04] That's not the case. Uniquely, there's these di and tripeptides that are actually getting there much faster, 189% faster than a single amino acid. My thought was, “What if we take this key driver of muscle protein synthesis leucine and see what happens?” Because it's not about the total amount of leucine that you take, it's about what we call PK or pharmacokinetics. It's about how quickly it spikes in plasma, not about total amounts, how quickly it rises. That's how a lot of the signaling works, is how quickly things rise. And so, in fact, that is the case. When we tested it, dileucine was 60% better, in some cases 80% better at increasing muscle protein synthesis activation, and it's 185% better over control in terms of the increase. So, it's market how much it's increasing muscle protein synthesis. And when we just finished a training study that's about to be published, and I mean, I can grab some quick numbers here, I'm looking at it because we just got this data, it's not even published yet.
[00:20:14] So we saw 220% more reps over baseline, which was 16. This is with a leg press, 16 more with the dileucine, and only 5 with leucine, which is massive in this. I believe it was a 12-week training study. One rep max with leg press, 189% increase over placebo, total strength of 144%. 159% greater muscle protein synthesis activation over baseline, 60% over leucine, and then again, it's 185% faster. So, it's groundbreaking what this means, right now, this is for a sports nutrition brand, and that's certainly where we'll be looking. But there's massive clinical applications that we're excited about as well with sarcopenia, cachexia, etc. So, this is really exciting for us. And then this is on the anabolic side of the equation. MuscleTech actually has my ingredient paraxanthine, which we'll talk about in a little bit, is the metabolite of caffeine. TSI is the distributor, TSI makes HMB, and they've worked with Abbott, for example, for years. That's a leucine metabolite that's anticatabolic.
[00:21:30] So, this HMB free acid, which is really the best form, is a product called Clear Muscle that MuscleTech makes. What's really cool is if you combine these two, now you have anticatabolic HMB-free acid, anabolic dileucine, the DL-185. And so now you're really skewing heavily net muscle accretion in your favor. And what's crazy is all of our data right now, and I'm going to mention this again with paraxanthine, all of our data now is on young adult males that are highly trained. So, we're talking like 18- to 23-year-old males. But what's interesting, like, we've seen this with our rodent studies, but we're excited to get these studies with humans, is that when you're talking about just even men my age, I'm about to turn 50. You see anabolic resistance, leucine resistance as we age. And that could because of declining testosterone and other androgens. It could because of insulin sensitivity. There's another a number of reasons that we could talk about anabolic resistance or leucine resistance.
[00:22:43] My guess is it's going to be a massive difference like if were to give this to 50-year-olds, 60-year-olds, people like that, people that aren't trained, etc. We're going to see bigger differences. And certainly, young men that are trained that have super high insulin sensitivity, that have high androgens, are super healthy, they have testosterones that are naturally 800 or whatever. We're seeing pretty big differences. I just gave you huge numbers. But my guess is they're going to be even more crazy when we start looking at an aging population. And also with females, especially females that aren't trained or that are a place where hormones are declining, etc., like premenopausal, perimenopausal, postmenopausal, kind of in that range too, so that's exciting.
Cynthia Thurlow: [00:23:37] It is exciting. Of course, selfishly, I was thinking my population, definitely the women that listen to this podcast north of 35, perimenopause and menopause, they're probably all thinking about when is the research going to be done on women? Because we know sarcopenia accelerates after the age of 40, and even more so when we're dealing with women with low estrogen, high FHS, high follicular stimulating hormone, and women going into menopause is far more catastrophic metabolically, than it is for men to go through andropause.
Shawn Wells: [00:24:09] Yeah.
Cynthia Thurlow: [00:24:10] And so I think this is really exciting, because how many women do we both know who maybe they didn't lift in their 20s and 30s, they didn't know any better. They get into their 40s, they're going to do the long-haul marathon, they're going to run 8 miles every day. They're very catabolic, they're really breaking down what muscle they have left. They're becoming more insulin resistant. And this is where strength training, stimulating muscle protein synthesis, and the other side of that is this protein leverage hypothesis, we know that we need more protein with aging and not less. So, if you thinking [unintelligible 00:24:46] with your 20 g of protein once or twice a day, that's just not enough to stimulate that muscle protein synthesis or even hit that leucine threshold.
Shawn Wells: [00:24:54] Exactly. So that's a great point, Cynthia, is that there is a refractory effect on these amino acids, including leucine. And what that means is it's not a question of how much you take. So that's what I was saying, when there's more insulin resistance, more metabolic dysfunction, when there's less androgens, as we're aging, it's going to take, yes, potentially a greater amount of leucine. But really, it's not just that it's a faster amount of leucine. And so at some point, it actually just becomes difficult to figure out how to stimulate muscle protein synthesis. One of the ways could be, I'm saying is, HRT, maybe like taking DHEA, testosterone, estrogen, like bone and etc. And then maybe taking something, obviously exercising is going to be great, but things like metformin, berberine and whatever, to improve insulin sensitivity or ketogenic diet, etc., fasting, which you're a big fan of. All these things that are going to improve that insulin sensitivity factor. So, yes exactly, that's a great point. So, thank you.
Cynthia Thurlow: [00:26:04] No, thank you. And for validating the HRT, I just interviewed Dr. Lisa Mosconi, who's one of the four mount menopausal brain health researchers. And we were talking all about HRT and how we got kind of so off course post WHI. So now that HRT is becoming more commonplace for men and for women, I think that ultimately benefits us when we have more choices, not less. Now, you mentioned paraxanthine. Let's talk about what it is. I'm a fast metabolizer of caffeine. So, I find this really interesting. You mentioned it's a downstream metabolite of caffeine. So, what does it do for us? Is it stimulating? Is it stimulating without being jittery? Like caffeine can leave us jittery if we have too much of it?
Shawn Wells: [00:26:47] Yeah, so. I mean, here's an example right here. I'm actually drinking this Update Energy Drink, which has paraxanthine. This is EuphoriQ, which is a MuscleTech product. These are the first two products to launch. There's about 20 products now if you look up, paraxanthine or enfinity is the branded name. So, what it is, is paraxanthine is one of the three methylxanthine metabolites that are created from caffeine. And when you consume caffeine, it can break it apart into three different things in the body endogenously, and it can become theobromine, which people kind of identify with chocolate and probably have heard of. And then theophylline, which is a controlled substance, a bronchodilator, fair amount of side effects and affects blood pressure and heart rate and all those things. And then it can become paraxanthine.
[00:27:37] About 70% of the total metabolism becomes paraxanthine, of caffeine. The problem is, so you may assume the natural assumption is, “Well, if I've had caffeine, I've had paraxanthine.” Yes, [Cynthia chuckles] and there's a kind of qualifier there in that your CYP1A2 gene, and how you metabolize caffeine, the cytochrome P450 pathway with the liver is going to dictate that. And so, there's a lot of bio-individuality, meaning there's a lot of variance in how we person to person metabolize these things. So, it can be a half-life of one and a half hours. It can be a half-life of ten and a half hours. That's like a 7x difference between how we metabolize caffeine person to person. So, we may think we're talking about that same substance that's in the Starbucks quad shot or whatever it is you're having, or the bang or the Monster or whatever, but it's not the same.
[00:28:44] One person, a fast metabolizer, can have it and then go to sleep 2 hours later, and then someone else can have it in their system three days later. And this is a very different thing. This is why I'm one of those you're a fast metabolizer. I'm a very slow metabolizer where if I had a Diet Coke at lunch, I'm not sleeping well. So about 60% of us are slow metabolizers. And we get this anxiety, sleep disruption, brain fog, jitters, all these kinds of things that are associated with being highly caffeinated. And that's the thing, when we're stuck in kind of that caffeine space, that's almost where all the side effects are. And paraxanthine is actually where almost all the benefits are. So yes, it will convert to paraxanthine, but the question is, how long and how fast does that take? You are kind of getting the slow drip over potentially days, instead of just getting it at once. And you're still dealing with theophylline, theobromine, and caffeine itself.
[00:29:51] So if we can cut those out of the equation, go straight to the thing that really has the benefit, then that's where we get a very clean experience without all the side effects. And that's what we're consistently seeing in our research. We're at about 13 studies now in 23 patents. For example, one study we did with a 10K with athletes when we tested them, kind of on a multitasking test, if you will. Even though really, it's more like task switching is kind of the better term because no one really multitask. So, like pre-race and then after race, we saw a significant increase in mental errors for those that are taking caffeine. And we saw a significant decrease in errors for those taking paraxanthine. And then placebo was about in the middle. So, the delta between the two is significant. So, we actually see both are what we would call CNS stimulants, central nervous system stimulants. But the way they affect our physiology and the toxicity may be associated with them, and the side effects associated with them are very, very different. So, this is where we're seeing more, yes, you're stimulated with caffeine, but it's more of a frazzle, whereas with paraxanthine, it's more of a flow.
Cynthia Thurlow: [00:31:13] That's really interesting. And I'm sure for a lot of people, they appreciate the ability to focus. And that's where I think it's very much that bio-individual, like, just enough to get the nootropic benefits without the overstimulation, which I think is really exciting. Now, leaping towards nootropic agents, I know that we have some favorites that we both really like. Where are you right now, again, it goes back to that proprietary blend. But talk to me about some of your favorite nootropic agents and what these are designed to do. It's really like turning your brain on.
Shawn Wells: [00:31:51] So this one, I would say it's a little bit gray market, but, I don't know if it, “occurs naturally,” but it is a nootropic. I have been testing it, and I really like it. So, if you're interested in BDNF, brain-derived neurotrophic factor. So, this is one of the keys to what we call neuroplasticity. So this is like, the way that you learn fluidly versus crystallized intelligence. Crystallized intelligence is we actually get smarter as we age, crystallize, because we kind of make our box smaller and smaller and smaller and we learn that, like all the shortcuts. Fluid intelligence is that dynamic intelligence, that resilient intelligence, where we can take on new tasks. And that's really associated with this protein, BDNF, brain-derived neurotrophic factor. And there's some other ones too.
[00:32:42] Interestingly, mTOR. We can go back to some of those other ingredients that I was talking about, and that's really some undiscovered country that I've been looking at is mTOR for the brain. There's a lot there, but there's also NGF, which is nerve growth factor, that's associated with these as well. This ingredient has been shown to be the most effective thing that I can find to increase BDNF. By the way, our preclinical data with paraxanthine shows-- increases BDNF as well as serotonin, dopamine, acetylcholine, increases glutathione and catalase, reduces oxidative stress. As a result, increases nitric oxide, decreases beta amyloid plaque. It's really potently protective to the brain, so that's exciting. But along those lines of neuro protection and nootropic, which is what I love about these ingredients, is they're really bimodal in that sense.
[00:33:42] What is increasing acutely your brain to function in the moment is also things that are healing the brain and protecting the brain from kind of suboptimal function and aging. So, this is called, [chuckles] this is a lot. 4’-DMA-7,8-dihydroxyflavone. And the DMA stands for dimethylamino. The precursor to this is, so this is the metabolite of the precursor. The precursor is just called 7,8-dihydroxyflavone. But both of these have been shown to dramatically increase BDNF. And this one may be the most potent. So, it's 4’-DMA-7,8- dihydroxyflavone. And it's something that I've been playing with. Now, more on the natural side of the equation of supplements and even food is just polyphenols in general when I study them, and certainly, like, I go through this a lot in my book, THE ENERGY FORMULA, like the blue zone diets. And what do they have in common? High polyphenols. Almost every polyphenol I've ever looked at increases BDNF. Catechins with coffee and chocolate, EGCG with green tea, quercetin in onions and apples, pterostilbene in blueberries, resveratrol, red wine, apigenin with parsley, fisetin with strawberries.
[00:35:02] All this stuff is potently protective for the brain and also helps control blood sugar, and is therefore like protective against metabolic syndrome and metabolic dysfunction, which is something that 87% of Americans have. Almost 9/10 Americans are metabolically dysfunctional. So, this is a really, really interesting ingredient. And certainly, like a pathway or a category to look at is BDNF and neuroplasticity in general. I think it's very exciting when it comes to a real anti-aging. If we can protect the brain, then that's really exciting. Another area that I could just throw out that there's almost no research in, but I really want to explore along these lines, is a category called psychobiotics. So, this is going to be probiotics for the gut, as well as prebiotics and what we would call postbiotics, which is things like butyrate and other short chain fatty acids that are going to affect the brain and how it functions.
[00:36:08] We know that 70% to 80% of your immune systems in the gut, 70% to 80% of your neurotransmitters are in the gut. This is where a lot of your health function lives, obviously, in the gut. We're hearing this more and more. There is this class called psychobiotics of probiotics and these other compounds that could potentially affect your brain health. So that's really exciting to explore. It's a really new category. I wouldn't trust anything really right now coming out there, but I think there's going to be a lot of research forthcoming over the next 10 years or so.
Cynthia Thurlow: [00:36:43] I think it's so interesting, and for anyone that's listening, when we talk about brain-derived neurotrophic factor. It's like fertilizer for the brain. This is why it's important to continue learning new things. As Shawn mentioned, it's very easy to get in a box, like where you just do the same thing over and over again, looking for shortcuts. It's actually important for us as we're aging to make sure we're doing new things. And my family laughs at me. I'm always trying to do different things, standing one leg while I'm trying to do-- It's like the flexibility piece. It's important for proprioception. The point being, learn new things, make sure you're stimulating your brain. That's certainly important. I'd love to talk about sleep stacks. Sleep is one of those for many middle-aged women, really an evasive, challenging component of trying to live a healthy lifestyle. I thankfully think I have dialed in on what I need to be doing for my sleep, and that includes a bit of HRT. I think that makes a huge impact. But for you, what are some of your favorite nutraceuticals or supplements? When you're thinking about sleep support for, let's just say, middle aged people, we can say men and women, that's fine, but what are some of your favorite things to consider?
Shawn Wells: [00:37:56] I mean, to your point, hormone optimization is going to be important in working with endocrinologist or whoever, like a functional doc around that would be ideal. It's become polarizing to talk about melatonin. Speaking of HRT, it is a hormone, but I do think it can serve a role. Now, I got some blue light blocking glasses here. These are great in the evening. And I have lred lights behind me and I have a little box I travel with, that's great to get me ready in the evening. And all these things are great. And some people are like, “Well, if I take melatonin, it will stop my endogenous production,” and there's a whole rabbit hole that I could probably talk about for an hour alone on endogenous versus exogenous and feedback loops, etc. But what I will say there is your bio-individuality matters, the dose matters, the timing matters, what you're going through in terms of your environment matters.
[00:39:00] So it's not that easy to just simply make blanket statements. So, what I would say there, as we age, melatonin tends to decrease often like these other hormones. And with the amount of junk light, blue light that we're getting from devices, from fluorescent lights. So, from your TV, from iPads, from cell phones, from laptops, especially in the evenings, especially if you're in a dark room. Oh my God, it's the worst thing. Especially if the phone, you're on it, [chuckles] if you're in a dark room, the cell phone's bright and it's close to your eyes, you're pretty much saying, “Zero melatonin will be released now. So be careful with that.” So just keeping that in mind, I like playing with the idea of working with, I've gotten the 0.3 mg melatonin and I've been playing with kind of dosing it through the evening because really, it's not meant to just knock you out and be directly for sleep, like an Ambien or a Lunesta or something like that. It's meant to kind of initiate the process of being sleepy.
[00:40:11] So, it's actually better to take it several hours prior to bedtime, not at bedtime. And what would be even better is if you're kind of spacing it out a little bit and if you are wearing your blue light blocking glasses and all this thing, not eating too late, some of those things would be helpful. So beyond that, I like things that relax me more rather than things that are highly sedative. I think in time that's probably not a good path to go down. I think it's better to get into ease in the evenings. It's good to not watch TV. That's high violence, high sex, high dopamine, high stimulation, highly controversial news and Game of Thrones and the baseball game [Cynthia laughs] that's tied up, whatever. All this stuff is actually a lot for our nervous system in the evening. So, I would find ways to read a book in the evening. I would find ways to wind it down in the evening, I would be off devices at least 2 hours before bedtime in the evening I'd be taking that light dose of melatonin a couple hours ahead in the evening. I would take magnesium, like a fair dose before in the evening, then sleepy time tea and those kinds of things I like. That's a nice process to have something relaxing.
[00:41:30] There's a lot of things I've used now, if I have found that for me, this has been the case, like, anxiety is a big part of it. And this is something to admit, like that we as entrepreneurs or parents, we get wound up about what does tomorrow look like as we're wrapping down or winding down our day. If that is the case, rather than reach for alcohol, which will impair your sleep quality. And by the way, if you're going to drink alcohol, much better earlier in the day, in the evening, terrible, terrible for your HRV. So I like things, there are some anxiolytic supplements that I would reach for, something like L-theanine, which happens to be in green tea and smooths out caffeine but used on its own, I really like. It's also something that helps you achieve the flow state. So, it's really nice with these kind of nootropic supplements because it gets you more in that alpha brainwave state. And then there's some really interesting ones that I've been looking at, from magnolia bark. There's the honokiol ingredients, and then there's even a metabolite that's kind of gray market. I'm not sure if it's fully tied up with what I call warfarin drug status in Europe or something.
[00:42:44] It's called dihydrohonokiol-beta as its metabolite. But these are pretty strong like anxiolytics to help you relax. And then beyond that, I really like the adaptogens in general. You know, I said the word bimodal before, adaptogens are bimodal in that they're increasing your resilience. So, what that means is instead of something like caffeine, which comes at a cost, something that's bimodal, it will improve your sleep and your focus and energy. Why? Because it's increasing your resilience, your, what we call allostatic capacity, your capacity for stress. And stress isn't a bad thing. Chronic stress is a bad thing. So stress helps us adapt, and that's called hormesis, and that increases our allostatic capacity, or stress bucket. And so increasing resilience increases that stress bucket. And therefore, we can handle more. Therefore, we can sleep better and have more energy. So that's the idea of bimodal. And that's where adaptogens are really interesting. And if we look at, throughout kind of the history of humanity, the most popular, most fascinating ingredients that have stuck around for thousands of years are always the adaptogens. If we go to India, it's ashwagandha. If we go to Asia, it's ginseng. If we go to South America, it's maca. We go to Russia, it's rhodiola. These are very exciting ingredients that just tend to make us more resilient.
Cynthia Thurlow: [00:44:18] Yeah, I love that. I am a huge fan of adaptogenic herbs, and what I love about things like ashwagandha, as an example, is it can be both tonifying and stimulating. And sometimes people take it before bed, sometimes people take it in the morning. I especially love magnolia bark, so I love that you brought that up. And there's a proprietary blend of magnolia bar called Relora.
Shawn Wells: [00:44:40] Relora, yeah.
Cynthia Thurlow: [00:44:41] And so that's how I know it.
Shawn Wells: [00:44:43] In that case, that's fair because they did studies on it. [Cynthia chuckles] So I will grant that proprietary blend because they did studies on that blend so that's fair.
Cynthia Thurlow: [00:44:52] Yep. So that's a good indication of that's one of those probably rarities where they've done research on those specific areas. Okay, let's talk about metabolism. As you mentioned, appropriately, 92% to 93% of Americans are not metabolically healthy. Huge focus of this podcast. Talk to us about the differences between dihydroberberine versus traditional berberine. I do not tolerate berberine. It gives me lots of digestive issues. I know that dihydroberberine tends to be more bioavailable, and I'm assuming, less gut-related issues.
Shawn Wells: [00:45:25] Yeah, exactly. So that's a great setup. Berberine works on this AMPK, AMP kinase pathway. And, by the way, new data, GLP-1 agonist, which is really exciting. I have the drug here if you're interested. I have all kinds of drugs and supplements. It's called Rybelsus, that's kind of like semaglutide or things like that. So, GLP-1 agonists have taken a hold of humanity at the moment through the drug companies. It's the greatest thing ever according to them. They do tend to have GI distress issues in general. Again, may not be the best thing. We don't have a ton of data. Ozempic is another example. But what's interesting is that pathway is becoming very big focus. But to go back to berberine, berberine is in, I always say this wrong, like ayurvedic. Someone's going to get mad at me. I can never say it right. [chuckles] Indian traditional medicine is, where berberine comes from. So, it's been used thousands of years. Berberine does help with blood sugar management. It's really impressive.
[00:46:36] We're finding more and more mechanisms improving dyslipidemia, inflammation, etc., etc., etc. And what's interesting is berberine is converted in the gut to dihydroberberine. And then back at the plasma, it's converted back to berberine again. So ultimately, berberine is the effective ingredient in plasma. But what we do when we go to dihydroberberine directly, we skip all that bio-individuality and gut microbiome differences and then potentially GI distress differences, and then the bioavailability differences that we see person to person with berberine, we see huge differences. So, in general, we're seeing about 4 to 6x better bioavailability with dihydroberberine, we do see much lower GI distress. So, this lowers the doses. What's cool too, is we're also seeing with dihydroberberine that it's lasting about twice as long in plasma. So, we're only needing to dose it twice a day versus three with berberine. So really the same benefits in terms of net effect, but skipping a lot of the side effects, much more potency, lower dose, lower frequency, etc.
Cynthia Thurlow: [00:47:51] Yeah, it sounds like a win-win to me. And in terms of other supplements that you like for metabolic health, whether it's myo-inositol, chromium, are there other things that you like to utilize or that you like to see? I know, again, the proprietary blend stuff. I'm just talking pure single ingredients or blends of ingredients that you like.
Shawn Wells: [00:48:10] I mean, both of those that you mentioned, I think are absolutely, when you look at people that are diabetic or borderline diabetic, you tend to see chromium very depleted, very huge difference to like someone who has normal glycemia. So, absolutely, we do see benefit to supplementing with chromium. You know, make sure to not chronically dose super high chromium over time. It is a trace mineral. And minerals do compete, it has to do with valences and doses. And then if you take too much of one, you can deplete another. So, I would probably look to get a formulation that has a broad spectrum of macro and micro or trace minerals that includes a bioavailable source of chromium. I do tend to like across the board with minerals, the organic acid. So, it would be things from the Krebs cycle or the citric acid cycle, like citrate malate. But probably even better is amino acid chelates. So, these are the minerals bonded to the amino acids. So, think of, we have magnesium, for example. It's magnesium threonate, which is threonine that's attached to it or something along those lines. We tend to see the best bioavailability there.
[00:49:30] So, yes, I agree with those. I think those are great choices. Again, going back to the polyphenols and how having a high polyphenolic diet in general, we are going to see pretty big effects on blood glucose and one of the biggest things you can do. I'm kind of steering clear of all my biohacking kind of info because I'm just focused here on supplements, but is just doing what I would call postprandial stroll where after your meal, you take even, like, a 10-minute walk. I'm not even talking about a jog, a sprint, I’m not talking about 30 minutes or an hour, I'm not talking about going to the gym. I'm just talking about directly after your meal, walk for 10 minutes. That's it. And you'll see a huge difference in your blood glucose. It'll upregulate, GLUT4 translocations, like pushing glucose into the cell. And especially if you're kind of more on that insulin-resistant side of the equation, especially if you're someone that kind of, like, after you eat, you get the sleepies, take a little walk. And there's other benefits to that too. You're getting your steps, you're getting more blood flow, you're moving lymph. All these things, they've shown how potently aging, like, being sedentary is.
[00:50:47] Even 45 minutes at the gym isn't undoing someone who's sedentary for 23 hours. They showed this in a study, like, “Yes, that's great to go to the gym, but it does take more.” They showed exercise snacks were more potent, like, so taking five minutes, if you did five minutes every hour throughout the day, it's more potent than having a compressed work out and then just being sedentary. So that's something that I would encourage. Two is like, that you get up once an hour, rest your eyes, especially if you're on devices, and then move your body. And it can be something simple. it can be air squats, holding a plank, doing crawling. I think we're not getting into what I'd call animal flow or kind of like this paleolithic movement or whatever you want to call it, where we just crawl, where we roll, where we do stuff. It's great if you have a baby or a dog or whatever, get on the ground. And even if you don't, just find ways to get on the ground, roll, crawl, step, all those kinds of things that we stop doing. Like sitting syndrome too, is along the lines with being too sedentary. You know, when we're on these devices, our head, cervical spine comes forward. As our pelvis comes forward, it kind of creates a C.
[00:52:10] So what your pelvis does, your neck does. So, when you put an arch in your lumbar and sacral spine, there should be like, if you think about that standard attention soldier, and you put that lumbar space in your spine, where you are kind of arched back. It's going to create a natural, healthy arch in your cervical spine as well. And then if you roll your shoulders back and kind of pinch together and press down on your scapula, now that's really healthy too. And now you're creating more space in your viscera and your abdomen, and your spine is in healthy alignment. Your head's back, and now you're not going to get the neck pain, the back pain. Not only can babies stay in squats for an hour, but you get people in Asia that are 80 and 90 waiting at bus stops, sitting in squats for an hour. We can't do that because we're sitting syndrome, we're on our devices, we're in our chairs, and our body is remodeling to keep us in this shape because it wants to use less energy. So, bone and muscle and everything is remodeling over years. So this is something that, again, if we can crawl, we can move, we can get into our body, we can dance. All of these things will allow for us to stay more limber as we age.
Cynthia Thurlow: [00:53:28] So, so important. In fact, I was talking to a family member, you're probably familiar with the term kyphosis, but there are definitely people that as they get older, they start to roll their shoulders forward, they weaken pectoralis muscles. They will actually get what is called a Dowager hump on their back. And trying to explain to a family member the person that has this problem, it's not necessarily reversible. It's like a slow crawling over time, this has been many, many years. This has slowly been evolving. So, it's like I'm always very cognizant of my posture, making sure my shoulders are back. This is why I do Pilates. This is why alignment and making sure that I'm not sitting all day long. And Shawn is bringing up some great points. You don't have to necessarily spend an hour and a half in the gym. It could be that you have micro doses of exercise throughout your day.
[00:54:20] I have two dogs. They get walked four times a day. I have a house that has three levels. We're constantly going up and down the stairs in between appointments because I think it's so important, and I'm very cognizant of step counts. So, I love that you brought that up as well. I want to ask you about one supplement that I myself started using about two years ago when I've been using quite a bit with patients and clients, TUDCA. Let's talk about TUDCA, because I think this is really unique. And actually, the more I understand about its benefits, initially I took it for one reason, and now it has a whole host of other benefits that I've learned about. And so, it might beneficial for listeners to understand what does it actually do in the body and why is it so helpful and important?
Shawn Wells: [00:55:01] Yeah. It's a really interesting one and even was kind of in semi-drug status at one point, but it seems to be compliant now. But as far as improving liver function, improving bile flow, we're seeing so many effects from TUDCA, and it really is potent in low doses, and we see people have more clinical results with it very quickly, often in weeks or even days. I'm seeing reversal of things like liver enzyme issues and things like that. So, yes, it's a very exciting ingredient, and just small doses seem to be very effective. I wish we had even more research than we do, but I can tell you just cases that I've seen from it anecdotally too, it's like labs are radically changing on TUDCA. I don't know. Are you seeing that with your patients as well?
Cynthia Thurlow: [00:56:01] I am. I'm definitely seeing improved digestion. I'm seeing some brain health benefits. And that's what the study I was looking at that was actually talking about the interrelationship of TUDCA, that gut brain connection or enteric brain.
Shawn Wells: [00:56:12] Okay. I haven’t seen that one.
Cynthia Thurlow: [00:56:14] Yeah. Helping people understand that there is far more to it than just digestive support. But for me, a lot of women seem to need that biliary support, whether it's they have viscous bile, because we've been conditioned to believe that fat is bad and we're eating a lot of seed oils and crappy vegetable oil. So for me, some of the benefits I've seen is room detoxification, improvement in digestive concerns, and then in a few people actually seeing improvement in sleep and other biomarkers. So to me, I think I understand probably a 10th of all the information that there is surrounding it.
Shawn Wells: [00:56:49] That's where I am at too. I hear, like, just miraculous. And it really is like, it's to the point where I've heard it so much, but I don't have all the data to connect to it, just have more anecdotal feedback, and I can connect the dots in my own head of potentially why—essentially what you're saying, I just don't have a lot of. I would love to see if he could send me that one study of brain, I would love to see that. But, yeah, that’s a great point. And to that end, were talking about earlier, when you mentioned digestion, I mean, the amount of, it used to be almost like a joke, “Oh, leaky gut.” That's silly and whatever that wasn't scientific. Almost like chronic fatigue syndrome and all these different things. But leaky gut is real, and a lot of people have it. And the amount of zonulin that's there and what we'd call, a lack of tight junctions, huge issue. And so, we're getting full toxic particles getting into the bloodstream [chuckles] and causing massive immune dysfunction, which is why people are having these immunological-- Anyone that's having, like, I would say that they didn't have this immunity issue or autoimmune issue or allergic type reaction when they were young, but they're having it now. I can almost guarantee you that is a leaky gut scenario. And by the way, going back to kind of that idea of the gut brain axis, we now see a new term coming up is leaky brain. And we're seeing that too, where some of these toxic particles are crossing blood-brain barrier and getting in to the bloodstream as well, and wreaking havoc systemically as well as cognitively.
Cynthia Thurlow: [00:58:31] Yeah, it's so interesting. And there were so many different questions that came in, but a lot of the questions came in around delivery systems of supplements. So, as an example, patches or transdermal supplements, IV therapies. My first question is, and I know you probably get this question a lot. A lot of people are using NAD. Some people are using it in a patch form, some people are using it subcutaneously, some people are taking it orally. What are your thoughts on NAD supplementation versus getting a boost in NAD from high-intensity interval training or other types of supplementation that can assist that from the back end.
Shawn Wells: [00:59:14] It's a very, very, very complex pathway. And the data just around increasing NAD itself is not ultimately that compelling unless a lot of other pieces are really there. And this is true of so many things in the body, where there's kind of the endocrine cascade, for example. There's just so much homeostasis and hormesis in the body where it's like this thing affects that thing affects this thing affects that thing, and it's just like a waterfall effect. And that's that cascade idea. But not to say that increasing NAD isn't without its merit, it certainly is. And there is certainly a correlation to having greater levels of NAD and therefore greater levels of ATP/cellular energy not being the term as insufficient cellular energy states. The acronym is ICE. When in the brain, it's referred to as brain energy gap, where there's a shortfall of ATP over the demands, and in time, that can lead to all these disease states, metabolic dysfunction, and more rapid biological aging over chronological aging. As for delivery of NAD, so NAD is not bioavailable orally, really. I haven't seen compelling data. maybe liposomal. I'm sure there's someone who's trying to say it is maybe, but I doubt it. Intranasally I will buy that, because that membrane with your nose, I actually have right here. Because, again, I'm this crazy guy. I have some oxytocin, ketamine--
Cynthia Thurlow: [01:00:52] I have oxytocin in my refrigerator. I haven't used it yet, but not the ketamine piece.
Shawn Wells: [01:00:56] So it would be a very-- this wouldn't be like a journey dose of ketamine or kind of like a psychoactive dose like that. That would be a far different dose. So intranasal, a lot of these things would work potentially, if it's dispersed correctly and if it's the right dosage, etc. So maybe intranasally, I would buy the NAD could work and work very well, potentially as well as doing IV. So that would be something to experiment with. But I can't say because I don't have the data. But I'd say there's a good chance. If you're doing it topically, no dermally, then as far as I really understand it, the particle size is too big. So you would have to do, I think it's called electrophoresis where it has to be like a charged patch, essentially it has a little battery in it. And so it's going to NAD+, it's going to be pulling that positive cation across the dermal barriers and to the bloodstream. So, like that, I've used them before it feels kind of like a light bee sting. [laughs] I don't know how you describe it, but it's not necessarily pleasant, but it's not like you can't deal with it either. But it's just something to be aware of when you use these patches. Again, maybe the intranasal might be easier.
[01:02:16] Now, IV definitely works. That's going to be very expensive. You know, $600 to $1,500, anywhere from 500 mg to 1500 mg, depending if you want to go through it faster than a two-hour rate. You're looking at kind of getting nausea sometimes. So sometimes they deliver it with Phenergan or something as well. And it's really crazy. As you increase the rate on the IV, you can literally go, um-mm-ha-um [Cynthia chuckles] It's instantaneous to where you feel the nausea and the increased rate, the drip rate. So that is something worth exploring. I do know some people on the autoimmune side that have done, something like 1000 mg to 1500 mg six days in a row and then have had tremendous effect. So that may be something. And I do see this idea with polyphenols, which we can get into. I [laughs] don't know how much time we have, but they do inhibit what's called NADase or CD38 enzyme, which is going to increase the amount of endogenously available NAD. So that's another way that you can attack this equation. But yeah, I do see those are potentially effective. But I'm seeing the idea being floated around that maybe you should, for three to six days, hammer high doses of polyphenols, but then not take them the rest of the month.
Cynthia Thurlow: [01:03:46] Interesting.
Shawn Wells: [01:03:47] So that's being kicked around. And maybe that's the case with this NAD as well, is like, maybe do these very high doses and then just leave it. There's a lot of anecdotal feedback coming in there. But again, we're pretty far out. that the data is not really there yet. As far as, some of the supplements that you could take. Yes, NMN, NR. I think NMN to me right now is far more compelling than NR, but we're also seeing NMN kind of being tried to be taken off the market by FDA, which is frustrating. I can talk about that for a long time. But that does seem to be the case, is that they don't want NMN on the market. And I do think it's fairly effective. It could be, again that it's higher doses of NMN. When people have taken the supplements, often they're taking 100 mg. If I'm to extrapolate the animal data, which isn't exact, like a lot of times in kind of pharmaceutical extrapolation, you use like skin surface area, body surface area. And it's not, that really doesn't correctly correlate, but it's one of the best tools we have. You'd have to really understand not just metabolism, but how each drug is metabolized. So anyway, you'd have to take around maybe upwards of 2 g. So that could get expensive too. But I do like the idea of if you're going to like hammer the NMN or NR, which again I prefer NMN or taking this intranasal NAD or the IV or the patch, the electrophoresis, maybe pairing it up with.
[01:05:22] I'm seeing the best polyphenol, the most potent one in terms of some data where they compared about 12 polyphenols, the fisetin, or some people say fisetin from like it's found in strawberries to be the most potent. Apigenin was pretty close too. And that one could be really cool at nighttime because it's a little sedative in higher doses. So that could be something to look at. And then just mitochondrially, maybe looking at CoQ10, PQQ, some of those kinds of things added to the equation could be interesting as well. And then I've worked on bringing antioxidant, it's a mitochondrial antioxidant to the market called L-ergothioneine. And, it could end up, we're looking at it being a new vitamin potentially, and that hasn't happened in, I don't know, 80 years. So, because there's a deficiency demonstrated for it. There's actually a cognitive deficiency. There's a unique transporter system for it just for this ingredient in your body, a transporter system for this, unique storage system for it, it's not found in your body. You have to get it from sources like mushrooms, certain beans, organs. So really interesting there. So that could be another one in the mix.
[01:06:33] And then I've also been really exploring spermidine as well. And that one not only mimics autophagy, which I'm sure all your listeners know well from fasting that you speak on, but also it upregulates mitophagy. So, autophagy at the mitochondrial level, which is very exciting big part of my energy formula, for sure. I had a podcast with a woman not too long ago. This is interesting. And she blew my mind when I was talking about spermidine. I'm like, “Yes, let me get this out of the way. It's in sperm.” And she's like, “Well, that makes sense. That's the seed of life.” And I was like, what. [Cynthia laughs] “My biochemistry brain had just never put that piece together.” I'm like, “Whoa, okay, that's cool. I never thought about it like that.” I'm like, “Mm, okay,” kind of like colostrum, let's say. It's so rich with immunoglobulins and growth factors and all these things. I was like, “Hmm, that makes sense. Okay, cool.” So those are kind of my mitochondrial ingredient that I throw out.
Cynthia Thurlow: [01:07:37] Well and I think there's a lot of misinformation. I do fervently believe that most people want to share good information, but I think there's so much chatter that goes on when we're looking at NR, NMN, NAD, what works, what doesn't work? The last question I have for you is about glutathione, because there's a lot of supplement companies that'll have oral glutathione. Sometimes it's liposomal. A lot of people like to give it IV. What is your preferred method for utilizing this master antioxidant? If you had to pick, your preferred delivery method, what do you feel is most efficacious?
Shawn Wells: [01:08:16] This goes back to the idea that you were kind of kicking around before, when you're talking about NAD, is that I like the idea maybe if you're immunocompromised, maybe hammering down on some of these things. But I think overall, you can 1, impair a lot of signaling in the body where oxidation is needed, let's say, post workout or for immune function or wound repair. There's places where oxidation actually signals things, and then when you take too high antioxidants, in some cases, they become pro oxidant, where they're doing more damage than good. So, knowing that it is the master antioxidant, knowing that vitamin C plays a role in all these things, natural antioxidant processes are taking place in a healthy human body as they should. I wouldn't recommend just constantly dosing these things. It doesn't make sense and it could impair your endogenous function and signaling and all these other things. And that's why a number of studies that we've seen where they have high dose oof certain antioxidants, we've actually seen counterproductive results-
Cynthia Thurlow: [01:09:29] Yeah.
Shawn Wells: [01:09:30] -including cancer and things. There's an example, where you're protecting cancerous cells. Well, that's not good. So anyway, I do like the idea at times, but I think what I prefer is N-acetyl cysteine, which boosts glutathione. There's a lot of great data around it. It's this sulfurous amino acid as well. And just, there's a number of ways that it positively affects you. And I would say boosts glutathione better than supplemental glutathione. So, you are right. I think there's something potentially compelling to doing liposomal or yes, in an IV it's cool. If you were in Vegas and you're hungover or you're sick or whatever, I get it. But, yeah, I don't like the idea of chronically dosing glutathione, and I don't like, yeah, doing that too often, too much, any of these antioxidants. What I've seen is, polyphenols. I'm going to keep going back to that kind of have antioxidant type effect, but are smart in the way they work.
[01:10:29] And I would lean more heavily on, that healthy diet or getting enough polyphenols versus taking massive amounts of just straight antioxidants. Because again, the data I've seen, there's often very conflicting results and even really counterproductive health results. So, you just have to be careful with doing that. So that would be my advice there. I would use N-acetyl cysteine if I was traveling, if I was sick, if I was hungover, if I had autoimmune issues. That could be a good one to use for, let's say, two to four weeks, maybe along with zinc, were again, high-dose zinc, great. High-dose zinc chronically not great, because again, we're getting into, you're going to have a shortfall of copper, and so you don't want to do that with minerals too long. But I like the idea of taking extra vitamin C, taking N-acetyl cysteine, taking zinc in some of these cases for, like I said, “A frequency of two to four weeks.”
Cynthia Thurlow: [01:11:28] Yeah. I think that cautionary tale is certainly an important one. And it's interesting. I was at a business event in early December and sat down next to a very recognizable individual on social media, has a big podcast, and it humored me because the individual pulled out of his bag. I mean, a massive. It's not like I don't take some supplements. I do, but I keep it pretty small and constrained. And it must have been 100 supplements. And it was this massive baggie and this individual just kind of tossed it down. And he was like, “That's just for the morning.” And I thought to myself, “Oh, my goodness, I can't imagine what you're taking throughout the day.” So, I think the point of caution is one that we should really reflect on lifestyle first, if you need a supplement. To me the sleep supplements are always going to be there, but most other things, I'm usually cycling them in and out of a curiosity. And I always like to guinea pig myself. Please let listeners know how to connect with you on social media if they have questions about supplements, that they want your input on something, how to purchase your book, how to find you.
Shawn Wells: [01:12:29] Well, first I want to go back just quickly. [Cynthia laughs] That's a great point, on intuition, trusting your intuition. I cycle things in and out. I think that's very healthy. Otherwise, your body does establish a baseline. I used to take way too many supplements like that. I do think that your cytochrome P450 pathway way ends up putting the brakes on all of it, and then you have crappy bioavailability of all of them when you're constantly taking a ton of stuff and your body's trying to like, say, “Whoa, whoa, whoa this is too much.” Another last point real quick that I've really been exploring is intention and affirmations and getting yourself into a parasympathetic state when taking these things. So thinking about the effects of it, getting into your breath, relaxing into it. Because I do believe that a sympathetic nervous system body is going to be resistant to using, absorbing, finding the home and properly making use of these supplements when you're not in the right state in terms of your nervous system, it's not in what we call rest and digest, right? It's in fight or flight.
[01:13:40] So these things will not be utilized the same way depending on your nervous system state. To a further end if you're in super flow state, if you're in affirmation state, if you use the power of placebo to where you're like, “It's going to affect me in an incredible way, then I think it's going to be hyper utilized in the best way possible.” Now, a lot of that's theoretical, but there's a lot of data on manifestation, affirmations, gratitude, the nervous system, those kinds of things. I think it's well founded. But as far as me, yes, this is my book, THE ENERGY FORMULA. You can go to energyformula.com. It's a biohacking book. There is a lot on supplements, obviously, in here, but a lot of other great stuff on nutrition, exercise, anti-aging, all those kinds of things. You can follow me at @shawnwells and I'm on all the platforms and so it's easy to find me there. If you go to shawnwells.com, I have a newsletter that's free that I break down research and go through all the things. And yeah, so and on my Instagram, I'm always giving infographics on how supplements work or what a good stack is, all that kind of stuff, so yeah.
Cynthia Thurlow: [01:15:00] Lots of great resources. Thank you again, my friend.
Shawn Wells: [01:15:02] Yeah, thank you for having me on.
Cynthia Thurlow: [01:15:03] If you love this podcast episode, please leave a rating and review, subscribe and tell a friend.
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