June 20, 2024

From podcast: https://bengreenfieldlife.com/podcast/ben-katz/

[00:00:00] Introduction

[00:00:48] Guest and Podcast Intro

[00:04:56] Ben Katz's experience in the world of mass spectrometry, an analytical tool used to uncover hidden components in various products

[00:07:14] Discussion into physical chemistry and the sophisticated instruments used in molecular compound analysis

[00:10:38] The workings of high-performance liquid chromatography (HPLC) and has chromatography (GC) and how they pair with mass spectrometry for high-resolution results

[00:11:55] Katz distinguishes between LCMS and GCM, their unique applications, and the significant costs associated with using these advanced instruments.

[00:18:36] Insights from Katz's work with the DEA and FDA are shared, focusing on the differences between tobacco-derived and synthetic nicotine

[00:21:44] The rise of synthetic nicotine and the importance of ensuring purity in nicotine products, including testing “Zin”

[00:24:14] Katz reviews “Lucy” gum and emphasizes the importance of testing vape products for impurities, including synthetic flavors

[00:29:59] The rise of synthetic nicotine and the importance of ensuring purity in nicotine products, including testing “Zin” products

[00:37:35] Complexities of analyzing kratom and kava extracts, highlighting the variability of user experiences due to individual genetics and specific compounds found in these substances

[00:41:35] Techniques used to understand drug interactions at the neuronal level

[00:43:54] Kava, its chemical composition, and its interactions with CB1 and CB2 receptors

[00:45:35] The chemical analysis of everyday foods and supplements, such as the ratio of theobromine to caffeine in chocolate treats like M&M's

[00:50:39] Discovery of appropriate theobromine to caffeine ratios in Kinder Eggs, ensuring safety for children

[00:51:38] Concerns about the widespread, unreported use of synthetic growth regulators in food products are raised

[00:55:45] Mushroom Product Market – natural products and supplements, including lion's mane mushroom, and discusses the labor intensity of growing mushrooms

[00:57:34] Closing the Podcast

[00:59:06] End of Podcast

[01:00:07] Legal Disclaimer

[00:59:06] End of Podcast

Ben G:  My name is Ben Greenfield. And, on this episode of the Ben Greenfield Life podcast.

Ben K:  So, chocolate produces theobromine, the major alkaloid not caffeine. In cocoa nibs right out of the chocolate plant, it's supposed to be 90% theobromine, 10% caffeine. So then, I start checking M&Ms, and I'm like, “Okay, why is the ratio switched? Why is there 90% caffeine, 10% theobromine?” Then, you're like, “Okay, that's really suspicious.”

Ben G:  Fitness, nutrition, biohacking, longevity, life optimization, spirituality, and a whole lot more. Welcome to the Ben Greenfield Life show. Are you ready to hack your life? Let's do this.

Well, folks, I don't follow many people on Instagram. I'm not one of those feed scrollers, doom scrollers, whatever you want to call it. But occasionally, I come across some kind of interesting channel. Most of them are art-based channels or occasionally people doing crazy acrobatic fitness or sports skills. But, I came across a scientific Instagram channel that I have been nerding out on. I don't even remember who sent it to me originally, but it's fantastic. It takes me back really to my days in college when I used to help run these machines called mass spectrometry machine to analyze different compounds and chemicals in the lab. And, don't worry, my guest will explain what mass spec is and how it works here shortly, but it's a way to identify and analyze different chemical compounds and just about any.

And so, my guest on today's show, his name is Ben Katz. And, Ben has an Instagram Channel. I'm going to link to it in the shownotes. By the way, Ben, what's the actual handle?

Ben K:  It's masspeceverything. I think if you search massspeceverything, you can find it on Instagram. Yeah, it's just one word. So, it's pretty easy. Yeah.

Ben G:  Okay, cool. Let's see, massspeceverything. And, by the way, if you're listening right now, if you go to BenGreenfieldLife.com/Spec, S-P-E-C, I'll include all the shownotes and the links and everything that Ben and I talk about.

But basically, he analyzes supplements and drinks and popular compounds that you may or may not have partaken in to see what's in them and if what's in them is actually what's in them, and if there's things in them that you might not expect to be in them. And, as a matter of fact, leading up to this podcast, I even took two things from my own personal stash up here in Spokane and I sent them down to Ben to analyze. He was kind enough to do so because there were two things I was getting a lot of questions about. I suppose they might fall under the category of vices. A drink that's supposedly a blend of kratom and kava called Feel Free. I've had many people ask me about wondering if what's in there is actually what's in there. And then nicotine gum, this Lucy nicotine gum.

So, every time Ben runs something, there's a cost involved. So, I didn't send him too much, but I sent him some Feel Free and some nicotine gum. So, in this podcast, I actually don't even know what Ben found out in those. So, I'll be the first to hear it along with you, but all sorts of other things that Ben analyzes. And so, we're going to get into some of his more surprising findings on this show. And again, go to his Instagram channel, massspeceverything. If you want to check out more in the shownotes at BenGreenfieldLife.com/S-P-E-C.

Ben, welcome to the show, man. 

Ben K:  Hey, thanks for having me. It's my first podcast here. So, we'll see if I can explain things. I did this, last joined an interview about nicotine pouches. And so, that was kind of my first, I guess, trying to get a little bit famous here. So, it's not one of these things that I intended, but I think people are identifying with some of the content. So, it's pretty interesting.

Ben G:  With the meteoric rise of Tucker Carlson, and from what I hear, his relatively hefty addiction to nicotine is probably good that you're analyzing all these pouches.

Ben K:  Yeah. This definitely on the fair side of proponent of nicotine and then the other side of the interview was Chuck Schumer who's clearly very anti-nicotine. And so, kind of the purpose of my channel is to kind of remain neutral. I like to be the scientist, the analytical chemist and I just to present kind of the facts of what is in things. And, I've tried to find my own space where I stay in my lane. I don't want to provide too much medical content because I don't have any really medical background, but I'm the chemist. So, I'm trying to be a trusted resource to try to help tell people what's in things, if products claims are accurate, and if there's things that aren't supposed to be there. And so, yeah, I try to keep it kind of center line.

Ben G:  Yeah. I love it. We'll get back to the nicotine, I'm sure.

But, I'm just curious, how did you actually get into this? Did you just grow up with a with a wish list for a mass spectrometry machine for Christmas or something?

Ben K:  Yeah. So, if we start way back, I'm an engineer by trade, so I was a biomedical engineer and then I kind of fell into mass spec. Back in the mid-2000s, everybody was interested in diagnostics with mass spec. So, there was just kind of clearly dream that you could just take a drop of somebody's blood and put it into mass spectrometer and you can diagnose every disease. And, you could tell if people are healthy or if they were sick. And, it turned out over the years, I joined a startup company who was trying to focus on instrumentation and using mass specs for diagnostics. And, it turned out to be complicated than that. That's what people have found out. So, it's now taking about, I don't know, 20 years to catch up to the dream.

So, early days of mass spec, people were realizing that blood was kind of complicated, but the degree that you had to get down to find the biomarkers. There was this magnitude difference. It was really hard to get down to these really minor differences that kind of tell you diagnostic information. But, that's kind of changed.  So, over the years, I went back from a company to academics. I spent seven years at Kansas State University. So, in Kansas, I was doing agriculture product with and stuff like that. And so, that's why I got interested in mass spec of products, supply chain, higher agricultural works. And so, I had a really interesting nuances as you look at how products are made and how crops are grown and how animal health. So, you get to see this health thing.

And then, about seven years ago, I switched, moved to California here. I'm at UC Irvine. And, UC Irvine, a known synthetic chemistry environment, so I do medical health stuff, right of drug synthesis support, right of new therapeutics support. And so, I get interested in my roots. So, in Kansas, I wanted to run food-related products and consumer products. And so, that's kind of where it started, coming back towards where people are a little bit more interested in what I'm doing.

Ben G:  Now, some people might not even be aware how mass spec actually works. When I watch your Instagram posts, I noticed that, for example, you have to kind of figure out how to liquidify something before you actually use a machine. So, explain to me how this actually works.

Ben K:  Yeah, there are kind of three stages of getting things into a mass spectrometer. The first one is just an extraction purification. So, you have a product. There's a potential bulk ingredients that are kind of fillers that you don't really want to analyze. So, you can kind of break it up into small molecules and macromolecules. And so, mass spectrometry aren't really that good at large macromolecules.

So, say you have a [00:07:54] _____ like a cellulose or just kind of a material that's taken up the [00:07:59] _____. Those are more difficult for us to analyze. So, the first extraction is I'm really trying to get down to the purified chemical compounds that the mass spec can actually analyze. And so, around that is just kind of experience on how to extract different products and getting them into a liquid solution into a solvent where you can see the molecules you're interested in.

Ben G:  Okay. I was going to ask you, you're probably getting there, but I noticed after you do it in the liquid and you put it in the mass spec machine, you see peaks that I'm assuming correspond to certain, if I remember back to college, certain masses of the molecules, right? 

Ben K:  Exactly. So, that's kind of step. So, the end of the process is once you get it into the mass spectrometer–you can think of mass spec as kind of like this intersection between chemistry and physics. So, we really got to get the mass molecule chemical compounds which are purified into this ionized cloud, into a phase where we can actually analyze them and detect them. Almost like it's a physical particle, so physics.

And so, yeah, everyone kind of talks about how you got these particles and waves and things like that in physics. So, what we're trying to do is get molecules into a way that we can analyze them inside of [00:09:12] _____ with physical chemistry piece of equipment. And so, there's a lot of complex physical properties and optics behind it. But basically, what you're doing is if you think of really small molecule, let's say that's a hundred and really large amount, say it's a thousand, they–

Ben G:  What are the units when you say hundred or a thousand?

Ben K:  Molecular weight, so grams per mole. So, that's kind of like you're thinking about grams per mole of a molecule. So, these are easy things to rip up and do research. So, if I see something that's had caffeine, you can go to Wikipedia and get the molecular formula and see the molecular rate of the molecular caffeine. And so, that's what I'm looking for. And, what mass spectrometer is able to use different separation techniques to get the molecules to hit a detector different times. And so, we get really, really good high-resolution masses, really good mass accuracy.

I have [00:10:02] _____ accuracy on the exact mass of these molecules, right? And so, we do that in an instrument called a time-of-flight typically. So, it's a long drift. The molecules have time to separate away. And so, the longer they travel, the more separation you get, the more accuracy you get at your detector.

Basically, if you see some of my videos, I'll step up through low-end instruments to high-end instruments. And so, you kind of got to use a bunch of different tools to kind of analyze a molecule in a bunch of different ways to get confidence.

And sometimes, people have heard about what's called HPLC, so high-performance liquid chromatography. And so, that's separations. So, let's say you do your extraction. Let's say you're looking for caffeine. So, you can go as a chemist, you can look at caffeine. So, you're going to go ahead and take your extract and try to extract out the caffeine with something [00:10:58] _____ but also try to eliminate all the things you don't want to look at and try to get, let's say, relatively purified compound mixture and extract with hundreds of compounds. All the compounds kind of in the same mass range, in the same class of molecules, but we're trying to take it down from hundreds of thousands of things down to thousands of things.

If I said a thousand of things in the mass spec at once, that would be just kind of a direct injection, it would give me great accuracy. It would be too much stuff for me to see. So, that's where this chromatography comes in. And so, those liquid chromatography, we're basically sending that mixture across what's called [00:11:37] _____ phase support. So, it's a bunch of beads, tiny particles that have different chemistry on them that allows the molecules to interact. And so, you're after bound bed and the molecules will separate all out and you can look at them individually in the mass spec. And so, that's called chromatography.

And so, I use two different types of chromatography, I use a liquid chromatography for liquid samples and then I use what's called GCMS. You guys see me do GCMS a lot. For the nicotine pouches, I'll use GCMS. That's gas chromatography.

So, in gas chromatography, you could think that all the molecules have different boiling points, right? And so, what you could do if you put all the molecules onto a [00:12:20] _____ inside of an oven, you could bake them off as you do a ramp in temperature in the oven and you can bake them off as individual molecules. So, everything would separate based on its kind of its [00:12:30] _____. And so, that's another way to do separations. 

So, both of these techniques have advantages and disadvantages. And, there's the obvious disadvantage that if the thing doesn't bake out at 350 degrees, if it's too big, I don't see it, right? It has volatilize for me to be able to see it. And so, that's kind of the distinguishing. That's kind of the difference when I decide whether I do GCMS versus LCMS.  The first decision is, is this compound going to work in an oven volatilization kind of breakout approach? And, there's a bunch of boiling kind of chemical bond issues that you have to work out on that side.

Ben G:  Can you use the same machine for GCMS and LCMS?

Ben K:  No, it's completely different machines. But, the backend, the mass spectrometer, they're different but they look similarly. So, the mass spec side is similar. But typically, you'd have these instruments. They're typically fused together. So, whether you call it tandem or inline analysis. And so, the LC instruments are separate from the GC instruments. Yeah. So, we typically have lots and lots of instrumentation and some redundancy on the mass spec side. Yeah.

Ben G:  Just out of sheer curiosity not that anyone would want one of these in their office, but how much does something like that cost?

Ben K:  So, between 600 and million dollars. So, 600,000 to a million dollars for one high-end instrument on the LC side. The GC side is nice because GC instruments have been around out longer. And so, the prices have come down due to competition. And, there's a hefty amount. So, I'd say the GC instrument I'm using is maybe between 100 to $200,000. And so, those are a little bit more affordable. And then, there's the low-end instruments. So, what we'll try to do is we'll try to keep projects off of the high-end instruments to keep the traffic down by using low-end instruments, which are usually in the 100 to 200,000 price range.

Ben G:  Alright, this isn't necessarily something you're going to put next to the air fryer in your kitchen.

Ben K:  Whoever ask this question is, when am I going to get a mass spec in my house or in my fed? I get this from [00:14:37] _____ all the time. Everybody like, “We want these things in phones.” And, I ask, “What would someone do with it?” Like, “What would you use it for?” And, the answer is people they have this kind of distrust in product labels, they worry about pesticides. So typically, these issues that you think you wouldn't really need it in your phone, if there was somebody out there, that's kind of some of the impression in my channel, it's like if you had a mass spec person you could trust, then you could steer these questions that you have to somebody you could trust. And, you wouldn't have to actually have these things in your phone. It doesn't seem like there's a lot of real-time need at the moment for them in a cell phone.

Ben G:  Well, wouldn't there have to be a great deal of engineering too to get them down to size because they're pretty large?

Ben K:  Yeah. And, there's engineering, but there has to have to be new physics invented. So, some of the ion optic physics is just not able to monetarize well enough. And so, there are some going at labs and [00:15:34] _____ that have worked on monetizing mass specs. And, they've gotten them down to in a moderately heavy suitcase table format. But, one of the mass specs that we have is probably small.  Yeah, it's a box. It looks like a printer. It's the size of a printer.

Ben G:  Yeah.  I mean, the ones I've seen are by the size of a mini fridge.

Ben K:  Yeah. So, I have ones in the size of mini fridge on wheels. I have ones that are 10 feet tall. So, they're huge ones. And then, the smallest I've seen them get it down [00:16:05] _____ make them small because there's so much equipment in there that when it breaks, it's so compact. It's impossible to get the thing opening. And so, I did find out is that on the mass drivers, they have mass spectrometers. They have detection stuff on mass drivers. So, [00:16:22] _____ right now who is a mass spec and the [00:16:26] _____. And, I was like, “You guys got to choose something really compact.” There's a small design out there that I make about that JPI decided to use. And, they said, “No, we're using the same printer size mass spec that I have. ” So, they based the design off the end that we are using. And so, that's as small as it gets. But if it's on mass driver, that's definitely the smallest it's going to get.

Ben G:  Oh, man. And, last usage question, then I actually want to talk about some of the things you've tested. How much does it actually cost to run a sample?

Ben K:  So, a lot of times people try to tie in or out of the instrument cost instrument maintenance cost to the sample. So, the sample itself, if you just lift up the things you needed to run the sample like a wire, like the dollar. The extraction side events are really aren't that expensive. So, just the actual materials cost is really probably a couple dollars. But, a lot of people try to tie in some instrument maintenance cost. And so, I'd say it'd probably cost between 10 and $50,000 a year to maintain an instrument. And so, we'll try to parse out some of that cost for operations. Just kind of mileage on your car when you're driving it. And then, technician cost. And so, we have set external rates. And so, I think it's typically about $150 a sample if we had an external client.

Ben G:  Okay. Okay, got it. Just for folks who are curious about sending Ben stuff, you might want to be.

Ben K:  Yeah, yeah. Reach out to me and see if the project works best. And then, I have started [00:17:59] _____. It's amazing. I have [00:18:04] _____ referring people too just because it's just too much for me to hand out at this point. Yeah.

Ben G:  Okay.

Ben K:  My general regions is to academics and research that's published. And so, yeah, it's kind of balance.

Ben G:  I get it. But, nicotine pouches are sexy. People want to see it.

Ben K:  Oh, my gosh. So, I didn't even realize how many people are using these things until I started raising about it. But man, they are popular.

Ben G:  Oh, yeah, just as popular as all these inhalers. A lot of people are just waking up and using throughout the day.

So, let's start there with nicotine. I'm curious what are some of the more popular ones that you've tested and what you found.

Ben K:  Yeah. So, my nicotine interest kind of started back with some of this California regulation. So, I worked with the DEA and FDA on some of the regulation around nicotine products. My first big interest on nicotine is, I don't know if anyone know this, but synthetic nicotine has kind of exploded onto the market. Nicotine for the longest time was tobacco-derived. I think only about two or three years ago I even saw synthetic nicotine come into the industry and the marketplace. And then, people realizing it, they prefer the synthetic nicotine. And, that was kind of the story that I liked. Okay.

So, I'm a synthetic chemist. As a biochemist, I understand the differences between a synthetic molecule, where you would basically get what's being advertised, right? So, if you say this pouch has nicotine in it, it's 100% clean nicotine. If it's synthetic, they go through great effort to make sure that the molecule is perfectly clean. Because of this synthetic nicotine industry, the extractors–so basically if you're making a nicotine product that's not a cigarette where it's just tobacco leaf inside of something or it's just tobacco leaf in there but you're selling a vape or a pouch and it's derived from nicotine or derived from tobacco, that means that you're doing my first step, that extraction step. You have to extract the nicotine out of the tobacco leaf and purify it in order to put it into something else.

And so, that's the part that was really interesting to me. The problem is that plants don't produce just one molecule. A plant is a complex metabolism. The secondary metabolism uses a cascade of enzymes. So, they're alkaloids, right? So, they don't just make one alkaloid, they make a bunch of them in various levels. And so, that's the complexity in extracting from tobacco is that not only do you get nicotine, you get a bunch of minor nicotine-related alkaloid impurities that kind of tag along. And, you could spend a lot of effort and cost, purify those impurities. And technically, that's really expensive. And so, some companies do a better job than others in purifying nicotine derived from tobacco.

And so, my first interest was checking nicotine products. The project started with vapes. The pouches weren't even on the market yet when I started. And, I was just looking to see if companies were telling the truth. So, if you were to say you had synthetic nicotine, were you actually using synthetic nicotine or were you trying to hide it and so that you are using tobacco-derived nicotine. And so, this distinguishing difference, it was kind of what led me to my interest in nicotine. So, that's kind of one of the first things I continue to check when I see these products is the synthetic nicotine claim true. And so, it's kind of an interesting difference.

Ben G:  You tested Zyn. What did you find in Zyn?

Ben K:  Zyn seems like it is a synthetic nicotine product. In the Zyn products, I don't see any tobacco-related alkaloid impurities. So, that suggests that it's purely synthetic. And, that's positive. You don't want to encourage people [00:22:06] _____ at the university. You don't want to encourage people to use nicotine products. You don't want to encourage kids to use nicotine products. From the chemist point of view, people are already using nicotine products. I can't control consumer demand. And, that's got to be somebody in the medical profession to go through and tell people not to use nicotine products. But, as a chemist, you want people to be given purified clean products. So, if they're saying that it's nicotine, you want to make sure that it's just nicotine. 

So, one of the worse molecules that can be in those is alkaloid called anabasine. Anabasine is considerably more carcinogenic. It's a really toxic molecule. And, depending on which tobacco plant you get your nicotine from, there could be varying levels of how much anabasine is in there. And so, that's a really good marker. There's a bunch of these. If you did your own research, you could look up all these minor nicotine impurities and these other alkaloids that are associated with the plant and how toxic they really are.

And so, I think a lot of the problems in smoking, it does have mind-altered effects. And so, I think that wasn't addressed enough when people talk about it.

Ben G:  Yeah. I seem to recall from your Zyn video, it was just basically synthetic nicotine and I believe something close to the amount that they said they had in it than some kind of a flavoring or a cooling agent. It seems pretty straightforward to me.

Ben K:  Exactly. So, that's the part that it got me interested. So now, we got a product, it seems I sorted out with the DEA, FDA, and a lot of this new regulation. We sorted out the synthetic versus tobacco derived nicotine. The tobacco guys just started cleaning up the nicotine [00:23:51] _____. The synthetic guys where they come into the marketplace and say clean synthetic nicotine. And so, now, I'm like, “Okay, I keep it but I'm not seeing as many problems with the nicotine anymore.” So, I'm like, “Okay, this product advertises nicotine. I can check it and it seems most of the time everybody is telling the truth.” And so, that's why I continue to check them. And, the gum that you sent me also is using a clean nicotine source.

Ben G:  Yeah. I sent you Lucy gum, by the way. Yeah, they have the pouches and stuff. I sent you the gum because a lot of people chew it. They've been a sponsor in the podcast before. So, I was like, “I know a lot of people are using this.” So, am I going to lose my sponsorship here from Lucy?

Ben K:  No. I think it's a clean product. I mean, it's a clean nicotine product. It is a nicotine product but it's synthetic and it does seem to be pure. And so, everything I looked at so far suggest it as advertised.

Ben G:  Have you ever tested a nicotine product and you were like, “Holy cow, this is not good. It's got one of those carcinogenic chemicals in it?”

Ben K:  To tell you the truth, it's typically vapes. They're getting rid of a lot in the vape industry.

Again, I don't know how much people are even checking these on the regulatory side, but on my side, it is much easier to check a pouch because of it being a nicotine set that's in a powder inside of a pouch.  It's a little bit easier for me to do my extraction. What is it, a PG, the EG, PG vape juice liquid. It's just ethylene glycol, propylene glycol liquid guru. And, it's a moderately challenging extraction to get the nicotine clean out from that liquid, that e-liquid. 

I've learned these impurities in these e-liquids, but generally over the last two years, the whole sector seemed to get a little bit cleaner, I've noticed. So, I haven't been seeing it as many impurities as I used to. So, I'm starting to be okay with the nicotine source a little bit. The reason I started focusing on the pouches is actually the flavors. So, I'm now more concerned about the flavors than I am. And then, it's not this idea that people are talking about. Typically, people say no flavors because they don't want to encourage children to use nicotine products and the kids would like the flavors more than plain.

Ben G:  Right, right, the classic bubblegum-flavored 10-milligram nicotine pouch.

Ben K:  You go any high school and they're still buying flavors. And so, the best place to smell flavored vapes is a high school parking lot. They're everywhere. And so, that type of regulation doesn't seem to really work so well.

But, my interest is the flavors could have toxic effect. And so, that's not being talked about enough. The mint molecules specifically, so I try to mention that in my spearmint Zyn video. There are definitely some flavors. If you start reading through the toxicity of wintergreen, not wintergreen oil but of spearmint oil and peppermint oil, there's molecule called pheromone, which is just a kind of a minty flavor that comes around with the oil. There's strict rules out there about how much spearmint oil you should consume a day because of high carcinogenic and toxic, some of these flavorings are.

And so, some of my concern was in conjunction with the nicotine, some flavors may not be as good as other flavors. And so, I am trying to kind of almost encourage the push towards synthetic flavors away from natural flavors in the same fashion that I was trying to push the synthetic nicotine over the naturally-derived nicotine.

Ben G:  Because with the synthetic flavors, you can dial in much lower carcinogenic potential because you know what you're working with.

Ben K: You could choose one or two molecules, right? You can say these two molecules, these are the first. We're putting in there. We've checked them. We know they have no carcinogenic potential. But then, you still see people sipping, they say, “We're just using spearmint oil.” And, that's really obvious. As soon as you see a product with spearmint oil, there's instead of another two peaks which are flavors, there's 30 or 30 peaks which are flavors, and there's a bunch in minor peaks. And, it's the same thing. If you get the flavor from a plant, you get all these tag-alongs. 

The next conversation that I like to have around those types of products is the flavor. And, rich flavors use natural derived–it's kind of weird, right? Because everyone's like, “Oh, I have natural derived flavors. Everyone wants natural.” But, in specific situations where you're not just chewing on a mint leaf where there's a lot of extraction chemistry going on in concentration, sometimes naturally-derived is not as good as synthetic. At least you don't get as much of what you're being told was in there. So, it's definitely not as clear.

Ben G:  Right. If you're looking for precision and predictability, then often synthetic is the way to go.

Ben K:  So then, if everyone's like, “Okay. Well, you've left with every single Zyn, which one would you recommend?” And so, I typically steer for people towards flavors like wintergreen because they found out that wintergreen oil is too expensive, to grow wintergreen. And, you can make synthetic wintergreen with methyl salicylate, which is like aspirin, essentially. That is my joke because if you take 60 Zyns, you get a tab of aspirin, right? But, since we manufacture so much salicylate already, salicylate is in a lot of products, including aspirin.

Methyl salicylate tastes just like wintergreen. So, if you look at a wintergreen Zyn, it's methyl salicylate. It's just one single line and you're like, “Okay, methyl salicylate, nicotine.” I don't [00:29:47] ____ behind methyl salicylate, but I like that when a product is one thing, because it's easy to regulate, it's easy to control, and it's easier to manufacture.

Ben G:  Yeah. And, I should name by the way as you already alluded to that despite this discussion kind of going the direction of cleaner forms of nicotine, folks, it is highly addictive and it can cause things like vasoconstriction, erectile dysfunction, headaches in a lot of people due to the vasoconstriction. You have the addictive potential of simply needing it to get by. There's a lot of things to think about. So, yeah. So, check yourself if you are using nicotine.

Ben K: But, for people that already hang of nicotine addiction and they're smoking cigarettes or they're using vapes, the pouches are giving a nice avenue for quitting. It seems to be a pure product than all other vapes that I've been checking. I like that they seem to be accurate in the amount of nicotine they're putting in each pouch. And so, there's 6-milligram pouches which allows you to wean off how many times you're using the vape and keep that higher level of nicotine and then you can transition down to a 3-milligram pouch. And so, other products that get people this avenue to quit.

My big recommendation of, you're big enough, maybe Zyn people listening in and the Lucy gum people listening in, I would love it if a nicotine company sold a zero-nicotine product. I feel the kids are going to be doing pouches, right? There's peer pressure out there. If you sold at the convenience store a zero-nicotine pouch Zyn that had the exact same flavoring as the other ones, it would give that avenue for the person to quit, to get off of it finally, and to still kind of work through it–

Ben G:  Oh, yeah, absolutely. You get the habit, you get the mouthfeel, you get the kinesthetic sensation of opening the can. That's a really good point.

Ben K:  Exactly. And so, what's the harm? And, if you're in your first regulation and say, “Hey, let's try to regulate this thing,” okay, [00:32:06] _____ companies to sell zero-nicotine products.

Ben G:  Yeah, just call it Zyn Zero.

Ben K:  Call Zyn Zero. And, the cool thing about that is I have so many people comment on the Zyn video. So, I'm starting to get this breath of knowledge of just what people think about them. And, it's really interesting. I thought it was a very male-oriented product. I didn't realize that the high school-age girls were using these things. And, the most interesting thing that I noticed that they kept commenting was that they liked the flavor, they liked the effect of hanging out with a friend and putting the pouch in. The thing they didn't like was that it gave them the jitters, that it burned in their lip, that it made them kind of sweaty. I was like, “Those are side effects of just the nicotine.” All the things you write are the things, the nicotine.  And so, they were just selling products that are just pouches with no nicotine. I feel like people may make the decision not to even include the nicotine on their own.

Ben G:  Yeah. You make a really good point too about the acidity, the esophageal irritation. A lot of people are on acid blockers and the issue is that the impact on the microbiome and on digestive capacity if you're chewing gum or using a pouch and then you sit down to dinner, you actually don't produce adequate digestive enzymes. Then, people get leaky gut, constipation, et cetera, and then it'll come full circle and tie that back to the digestive disruption that the acid-alkaline shift from having one of those in your mouth prior to a meal can cause. So, it is important to think about.

Ben K:  Yeah. I mean, I think people really like chewing gum. I start looking at gum because a lot of the same favoring agents that are in pouches are in gum. Almost on a extreme level. And so, the next thing that kind of caught my attention was this use of these synthetic cooling agents. Okay. So, I talk about these quite a bit. And then, at scientific conferences, I talk about these synthetic cooling agents. And so, it's kind of an interesting history behind these. If you guys did your own research, they're called WS3 and WS23 synthetic cooling agents. They're typically used in vapes. And, these things are invented did back in maybe the '70s for straight razors, for shaving. And so, these are menthol mimics. They don't have much of a minty taste, they just kind of have a cooling sensation.

And so, what they do is when you show it with a–I don't show with straight razor, but when we show it with a straight razor, it would hurt. But, the synthetic cooling agents actually are in the razor strip and blocks pain. So, they're short-term kind of cooling pain blockers. And so, they put them in shaving cream. So, all of a sudden, people started thinking, okay, vapes. Well, I haven't had a vape really hard. That burns. That hurts. But, what if we put synthetic cooling agents in there? Maybe all people that took these big rips of this compound and haven't hurt. And then, the same did with the pouches, it burns. And so, if I start putting in more and more of this synthetic cooling agents, which typically originally designed to be a really low concentration, not internal, just external on the surface of your skin. But, since they went into gum, it kind of gave them that avenue into the mouth and they're like, “Okay, so gum is not technically considered food. It was kind of considered a confectionary.” And so, then that gave them that.

So, they kind of been able to maneuver these synthetic cooling agents through the industry because of how regulation has changed around certain sectors. And so, whether we're typically early in, they're in products, then they got them into toothpastes and the flossers. And then, they're like okay, they're already in [00:36:14] _____, so let's put them in gum, the nicotine. And, she was like, “Alright, they're already in gum. We could put them in pouches.” And so, it's kind of that [00:36:21] _____. And so, these things are starting to be used to that more.

Ben G:  Yeah, the analgesic effects of mint are so interesting. Yesterday, I was reading a study in which they gave peppermint oil-infused water to runners and significantly increased time to exhaustion and reduced rating of perceived exertion. I even have this menthol spray out in my gym that's meant to be sprayed in the hands, then you huff it almost smelling salts. It gives you a lot of energy. Yeah, it lets you push harder. It does have a painkilling effect.

Ben K:  Yeah, it's interesting because from the scientific side, you think about these things as TRP channel modulators. So, the most common TRP channel people know about is capsaicin. So, TRPV was the vanilla TRP channel, which basically tells you of something hot and spicy, right? So, these are TRPM and TRPA channels which kind of affect cooling and pain sensation. And so, it's kind of neat to see these. You almost don't want to think of them as flavors. They are bioactive molecules that modify how TRP channels behave. And so, it's really interesting to think about how flavors really do have a bioactive effect and what they actually can do.

Ben G:  Yeah, yeah. Well, in addition to the nico craze, there's a big surge of interest in use of kratom now, a lot of times for the analgesic property, sometimes for energy, sometimes even as an alternative to opioids as an alcohol alternative. So, I took one of the popular brands. I get asked by a lot this Feel Free bottle. It's like sludge and a little blue bottle supposed to be kratom and kava. And yeah, I'm curious what you found.

Ben K:  Yeah. So, it's as advertised. I really dug in there and tried to find out if one, if it's got a synthetic opioid in it because that's the first thing that everybody was kind of contacting me about.

Ben G:  Oh, yeah. People have been asking me if it's got fentanyl in it, synthetic opioids, everything. Yeah.

Ben K:  Everything that I looked at in it so far, on targeted metabolomics on it, which is a really advanced way to send things through a database with 300,000 compounds in it, to see if I can pick out anything that really shouldn't be there. But, the overwhelming high concentration of exactly where it's supposed to be there, exactly what they're saying there. And so, it is kavalactones from kava. We can go through some of these kavalactones that I detected. And then, I'm going to butcher the name, but I think it's called like mitragynine.

Ben G:  Mitragynine. That's the extract of kratom.

Ben K:  Mitragynine. Yeah. And then, again, so I was talking when you have extracted products, both of these, you could probably make synthetic kavalactones because they're a little bit simpler, but mitragynine has so many stereocenters. It would be near impossible for somebody to synthetically make this compound. So, I think maybe somebody in a synthetic group has published a paper on how to do it. But, it's definitely going to be a product that's going to be naturally extracted from the plant.

And so, with that comes around a bunch of other mitragynine impurities you could call them or just related structures, right? And so, it is a classic real set when I extracted it out of the Feel Free and put it onto the mass spec. It gives you this cluster peaks that are about the same mass, couple grams mL different in either direction. That's a classic plant extract product. So, it's for sure a kratom extract. And then, the same thing about the kava. The kavalactones are big cluster of very similarly structured lactone products. And again, it's the same thing where it's just one big expected-looking massive peaks that are in there.

Ben G:  Yeah. Did you try to drink any?

Ben K:  I didn't drink it.

Ben G:  That stuff will light you up.

Ben K:  All these things scare me. I don't drink that much caffeine to tell you the truth. These things are interesting. But, I had a colleague try it and he said that it made him sleepy. But, I've heard very mixed reviews from people online. I'm just not medical, so I don't know the addictive effects of it but I've heard addictive, I've heard not addictive.

Ben G:  Yeah. It really depends on your CYP enzymes and how you're wired up.

Ben K:  I've heard stimulant. I've heard sedative. It's crazy. 

Ben G:  Yeah. It's kind of how you can be a fast caffeine oxidizer or a slow caffeine oxidizer based on CYP genetics. Some people feel horrific on kratom, some people feel really dialed in on kava, but then others feel sleepy because it's a little bit of an adaptogen. And then, some people feel kratom makes them drunk. Other people just get good clean energy from it. It varies widely.

Ben K:  Yeah, I've never tried kratom with it. I have tried kava down in San Diego. There's a lot of kava shops and stuff like that. And so, I've tried kava. It's just relaxing.

Ben G:  Yeah. I think there's a lot less concerns about it, especially from an addictive standpoint than kratom.

Had you tested any other kratom products?

Ben K:  I had a kratom project actually I didn't end up going for. There's a technique for neurologist and pharmacologist where you can actually tell how drugs work. And so, it's called voltage clamping and [product] clamping. And so, you can actually measure a potential across a cell using a really, really tiny microneedle. You can actually suction on or measure an individual neuron's potential. And, they can do it on channel. So, if you're talking about how a specific channel works.

And so, I had a professor that I worked on. He's very interested in a couple different channels. And so, we were interested in kratom for a while, about maybe three or four years, Ben. And so, we had a graduate student that went and got the kratom powder from probably every shop in Los Angeles and we checked them. And so, it's something probably that's all over the place, especially when you're buying the powders from different shops. I tested [00:42:42] _____ or the Feel Free you sent to me. But, the concentration of the kratom molecules in the Feel Free product was great. It's a concentrated product. That is for sure. So, that's a thing that I probably tell people.

Ben G:  Yeah. I think they have some kind of a fermentation process when they make it to where if you're used to a certain kind of kratom and then you try that. It comes across as way more powerful.

Ben K:  It seems [00:43:11]____. So, anytime I mention, it was like they're doing a fermentation. It typically is just liberating [00:43:19] _____ plants typically make things mimetically. Sugars onto it and things like that which will sometimes deactivate a molecule. And so, sometimes when you do a fermentation, it helps extract and liberate more of the active compound. And so, that's what I'm seeing. I'm not seeing [00:43:36] _____. I'm basically seeing it and its hydro and its dehydro form, which is just a double bond move. So, it seems to be very much as advertised.

Ben G:  Super interesting.

Ben K:  Yeah. The kava too. I just had to pull up here. So, a lot of people talk about kava, I guess is how you say it. I saw a kava in the sample, but I saw those yangonin. And, I don't know the differences but I'm into it. But, the yangonin seems to be the most abundant if you're going to research the kavalactones because kavalactones, they've very characterized really well. They're very abundant. And so, there's a lot of them. Where kava, it seems like there's just two. There's just the mitragynine and then it's got a bunch, it's a hydro, dehydro, deoxo. So, things that happen in extraction and storage can happen to it. but typically, those molecules just have ever so slightly different potencies, right? So, just like capsaicin. If you take a spicy pepper, that's old spicy hot sauce like it was fermented. It could change the flavor and the spicy pepper a little bit, but it's just spicy, right? There's no new effect that happens.

The kava is interesting. If you start digging through the kavalactones, they have seem to hit slightly different channels and specifically was when yangonin, it's kind of interesting because it seems to be a CB1 cannabinoid, CB1, CB2 cannabinoid binder. So, I don't know much about what people talk about with this yangonin. I was interested to see that the yangonin seemed to be the most abundant of the kavalactone.

Ben G:  Yeah. Well, that would certainly explain a lot of the anxiolytic effects of kava if it's interacting with the CB1 and CB2 receptors like that.

Did you ever test anything that was a huge shocker for you like the peaks that came up really were way off of what was advertised in the ingredients or things were in it that were way different than what you expected?

Ben K:  I've got two interesting stories I can tell you. Okay. So, the first one we just kind of made about everybody is caffeine. I've been really interested caffeine. Again, it's another molecule that's made synthetically in massive amounts for Coca-Cola. So, they call that caffeine anhydrous. Since caffeine can come from multiple different places, they've made strict naming ingredient names for them. So, if it's caffeine anhydrous, it's synthetic caffeine made synthetically from usually I think urea manufacturing. And, that's what you see in soft drinks in Coca-Cola. But, you could also have naturally derived caffeine. Typically, the required [00:46:26] _____ on to say naturally derived caffeine. And, that'd be from tea or green coffee. And, you could have minor xanthine that come along with it. So, minor caffeine impurities.

The thing that was interesting to me is I started checking chocolate. I got young kids. My kids had chocolate. I'm like, okay. So, chocolate is a caffeine source. And, that's pretty well-known and that's trusted. Anytime you tell people that there's caffeine in chocolate, they say, “Well, caffeine is supposed to be in chocolate.” But, there is a published ratio. So, chocolate produces theobromine. Theobromine is the major alkaloid, not caffeine. In cocoa nibs right out of the chocolate plant, it's supposed to be 90% theobromine, 10% caffeine. And, that is the way the plants metabolism is supposed to produce. The theobromine is the molecule you ran. That's your chocolate. That's what everybody's after.

Ben G:  Yeah, maybe arguably a little bit of the paraxanthine in there has a similar effect. But yeah, theobromine is the big hitter.

Ben K:  Yeah, that's the way after. So then, I start checking M&Ms and I'm like, “Okay, why is the ratio switched? Why is there 90% caffeine, 10% theobromine?” Then you're like, “Okay, that's really suspicious.” And so, you're like, “Okay, maybe it's something to do with chocolate manufacturing.” So, maybe it's Hershey's, maybe it's chocolate manufacturing. So, let's step it back a bit. Let's go to cocoa powder.

So, cocoa powder is called cocoa powder, but it's not just cacao but it's cocoa powder, and then some people really like cocoa mass. And so, I'll check. Let's say Trader Joe's cocoa powder versus Hershey's cocoa powder. And, the ratios are different. And, you're like, “Oh, something's going on in the cocoa manufacturing.” And then, you'll get cocoa liquor and the cocos liquor faction would be slightly different too. Okay. So, there's little effect in manufacturing chocolate for different products that's causing some of this increased caffeine.

Ben G:  And now, we know why when kids are running around hyper on Halloween, it might not just be the sugar, might be all the caffeine in the M&Ms.

Ben K:  And so, that's what I started to do. So then, I'm like, okay, wherever people [00:48:40] _____ this or people like checking caffeine was in candy because I'm not the first one that's probably thought about this. And, it turns out there are websites out there. I've been trying to work through and validate a lot of their numbers. But, candy bars have altered wellness of caffeine. It's all over the place. And, that is my first really interesting thing that I found is that some candy bars and candy I shouldn't give to my kids and some candy should be what I give to my kids. And, it doesn't seem to, was like, “Oh, you're giving them dark chocolate.” That doesn't seem to be. If milk chocolate M&Ms has a high caffeine, then we really should start going through and checking caffeine levels.

Ben G:  Yeah. And, by the way, obviously, dosage is an issue here. You say M&Ms have caffeine. Let's say there's 100, 150 milligrams in a cup of coffee. How much are we talking about in an average serving of M&Ms?

Ben K:  That's something I'm not going to comment on yet. We're trying to get to the bottom of it. And so, we're working on quantitative assays. The way that I approach it, we could talk about those. So, I'm thinking that we do it by serving, right? And so, it's kind of first, you're like, “Okay, how do you even normalize that?” Because you got one product is an energy drink and one is a drink and the other one's a powder and another one's a candy. And so, we decided we'll go ahead and start looking at this but we're going to start doing it by serving size. And so, would you say that a recommended serving size of M&Ms would have more or less caffeine than a cup of coffee? And so, that's the type of things we're trying to investigate.

So, yeah, stay tuned on the channel. We're trying to get more quantitative. Originally, my channel is not trying to be quantitative, but I keep getting a lot of quantitative questions. And so, I think I'm mainly originally interested in this proper chocolate ratio. So, I'm trying to check products right now not quantitatively, but just trying to see which products have what look like the chocolate ratio. So, I'm trying to see like, do you have theobromine than caffeine in your chocolate product?

And so, there are products out there that like–okay, so the most interesting one is this Kinder Egg. So, these kids land these Kinder Eggs. They're advertised, there's a toy in it, right? It's down at the kid's level in the grocery store. So, they always ask for them when you're checking out. And so, this is 100% absolutely with product designed for treasuring. So, if that has potentially caffeine, then we got a problem. So, that is one of the first things I went to and I was like, I was happy to find out that the Kinder Egg has the correct ratio of theobromine to caffeine.

Ben G:  Good. So, Kinder Egg is not going to suppress bone mineral density or stunt growth or make them grow crazy.

Ben K:  Yeah. So, that's kind of where I'm at, at the moment, on that project. And, we're trying to dedicate more time to some of it, to quantifying everything. It takes a bit more work to get to the quantitative level. You use an instrument called a triple quad mass spectrometer, which is kind of a dedicated quantitation instrument. And so, it's a little bit my work to get to that, but that's kind of the direction we're going.

Ben G:  You said there was one other thing though that you found shocking. I'm curious if you got one more. 

Ben K:  Yeah, yeah. Okay. So, it's a [00:51:43] _____ direction. Okay. So, I checked hot sauce and I was originally just licking at hot sauce because it's kind of interesting. And, I found a compound called diphenylamine. So, diphenylamine is — it sounds nasty, right? You're like, “What is this thing?” It's a synthetic molecule that's sprayed on fruits and vegetables. And so, it's what's called a growth regulator. So, what happens is you harvest your apples, let's say, and then if you have a harvest racket, they'll bring it to you and you'll eat the apple right away. So, we have to spray it on there. But typically, apples are put into cold storage and then the branch in the grocery store are out of the freezer. And so, this out of fridge. And so, this going into a cold storage and then coming back out of the cold storage, most fruits and vegetables get spots. So, they would get these little brown spots on them just because they went into the fridge and came out of the fridge.

And so, there's this compound called diphenylamine that you could just literally spray all over fruits and veggies. And, that will prevent them for having this cold storage problem. And so, I started seeing that. It tracks through like the hot sauce and the applesauce. And so, I was like, “Wow, they're really putting a lot of this diphenylamine onto apples and peppers.” Again, I have to get back to it and start trying to figure out the real levels. But, it was really concerning. You could do your research on the internet about DPA on fruits and veggies.

Ben G:  Yeah, that's what I was going to ask you. Are there health concerns with DPA?

Ben K:  Yes. All over the place, people talking about DPA. The concern I have is that but it's not being reported. It's not an active topic of conversation that you could maybe probably have options for people that don't want DPA and say, “Hey, I don't care of these brown spots in my apple.” Just that to it. But, since it's a post-harvest regulator, I don't think it's not organic. That's the weirdest thing, right? So, organic applies to how you grow the produce. Once you harvest the produce and you spit it with a post-growth regulator like DPA, I still think it qualifies as organic. And, I'm not the expert on this.

Ben G:  Pretty sure you're right that certified organic refers to herbicides, pesticides, filters, pre-harvesting.

Ben K:  Exactly. So, there's the next thing that I really wanted to start investigating more is kind of this broad use of post-harvest growth regulators that have been making it into to fruits and vegetables. And so, a lot of people are very health-oriented. “I'm just going to eat clean meat and fruits and vegetables and cook my food at home.” And so, I want this knowledge to be out there so people realize that the sometimes a little bit more to the picture on fresh fruits and veggies, specifically around the cold storage issue. And so, maybe there's need for, I don't know, just kind of another option. So, people are really focused on the way produce looks. It means the looks so perfect.

And so, maybe if the consumer wants changes, then the market will change. And so, I'm a very big proponent of consumer-oriented change. If the people are like, “Hey, we don't have these growth regulators anymore. We don't care if there's spots, give me an option.” Then, the market will fill that void. And so, that's kind of just trying to get that idea out there that there is this category of post-regulators that that could be on, even organic fruits and vegetables.

Ben G:  Do you get many people sending you supplements like capsules, tablets, soft gels, things like that?

Ben K:  Yeah. I've been slowly thinking about getting into that. I'm not doing synthetics at the moment. So, I started looking at creatine. I've started looking at caffeine like pre-workouts and things like that. And, I just started branching into mushrooms. And so, my next one I'm going work at is lion's mane mushroom. There's been so much. I've been getting it on social media as well. So much people. So many people talking about lion's mane and the effects of it on cognition and memory.

And so, to me, it's surprising that lot of these mushroom products are on the market because of how low intensive it is to grow mushrooms to a fruiting body. And so, anytime I see this kind of disparity where there's low price large quantity products that come from the natural source I start getting interested. Because I want to check it to make sure that it's legitimate and the consumers are [00:56:51] _____.

Ben G:  Yeah, you're on the right track with mushrooms because it can be grown on a starchy cheap medium and lined up with a bunch of —

Ben K:  Yeah, it could, even fruit, right? You could be growing mycelia in a spinning culture and that could be what you're selling. And so, in mushroom specifically, there's a kind of maturity issues of mushroom. They actually produce the secondary metabolomics that you're active. And so, for a chemist, it's great. I just take the powder they give me and check the molecule itself where, “Hey, does this actually have a [00:57:20] _____ in it? There was a lot.” And so, that's kind of the direction I'm going to go.

Yeah, I have started looking at supplements and confirming some things. But, I mainly focused on natural products right now.

Ben G:  You, good sir, are doing the world a very interesting service and I'm hoping that my listeners get a chance to check out your channel. I assume that's one of the better ways to support you is just go follow you and pay attention to what you do.

Ben K:  At the moment, I'm trying to [00:57:49] _____. I've been dabbling in monetization. But, right now, I'm not really focused on monetization. So, it's more just for me and just continue enjoying the content and [00:58:01] _____ and reach out. A lot of the positive from all this is I really say much from people commenting. A lot of people think that, yeah, I'm not even that big of an influencer, but the influencers don't read messages and comments. I take time to try to go through everything and respond to it myself. I've been keeping everything in-house and trying to manage things on my own. And so, I like hearing what people say. I like hearing people's opinions and suggestions. And, it helps guide some of the interest of what I'm looking for.

Ben G:  Yeah. Well, the page for everybody listening is massspeceverything on Instagram. And, I'll link to that and other things we talked about like nicotine and kratom podcast, other similar things I've talked about if you go to BenGreenfieldLife.com/Spec, S-P-E-C.

But Ben, in the meantime, keep going, man. It's an incredible channel and I enjoy watching your videos.

Ben K:  Alright, thanks for having me on.

Ben G:  Alright, folks. I'm Ben Greenfield along with Ben Katz, the mass spec guy signing out from BenGreenfieldLife.com/Spec, S-P-E-C. Have an amazing week.

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