Richard Bloomer: Many of us working in the area of dietary supplement research and nutraceutical research are aware of one another and the work that's being conducted.  We see each other at different meetings, etcetera.  I became aware of this through some reading that I had done and then a colleague of mine who actually works within a dietary supplement and contract manufacturing business.  He shared with me a product that he was looking into using the theacrine so I became aware, at first, I think, through that connection.  Then, from there, I started studying theacrine and really where it's been found in some of these different types of tea.  I think there's Ku Cha.  I'm not sure if that's the correct pronunciation but its K-U-C-H-A tea.

Unlike many of the other teas that are rich in caffeine, this particular tea seems to be very rich in theacrine, I think, at the dosage of approximately 50 or 75 milligrams per cup.  Some individuals are probably getting it and potentially feeling quite good with the use of the tea and not even realizing what they're consuming, but that's how I first became aware of theacrine, and then we've been doing some work with it over the past few years either as an isolated ingredient or in combination with caffeine as well as within a kind of a mix in its dietary supplement.

Jesse Lawler: So, biochemically, it's related to caffeine.  When it occurs naturally, is it replacing the caffeine within the plant, or do they exist side by side to some degree?

Richard: The different types of tea, historically, will have different combinations of the caffeine, and in some cases, the theacrine.  Structurally, they are similar.  I think theacrine, technically, is considered methylurate purine alkaloid versus caffeine or methylxanthine purine alkaloid.  They seem to have similar overall effects, albeit, we find, with the theacrine, people tend to not have quite the massive high, and then they'll fall out a couple of hours later, which is oftentimes what happens with the caffeine or the caffeine low.  They tend to have much more of a stable energy as well as a focus and just kind of that feeling of euphoria and focus, which I think a lot of people like especially if they have to sit at desk or do things in an office setting and they're using something like traditionally caffeine.  Maybe they don't want to sit down still after consuming a couple of hundred milligrams of caffeine.  They might feel like they need to get up and do things.  Theacrine does seem to help a little bit on that regard.

Jesse: How long do you see for the period of effects?  I know, for caffeine, the half-life for most people is around five or six hours.  Is it something similar for theacrine?

Richard: That's what we're studying now.  We have a paper, and I can't release a whole lot of details, but we have a paper that was submitted to the Journal of Caffeine Research, and we're finishing round one revision.  So, hopefully, we'll send those revisions back in and everything will look good to the reviewers, and that paper should be published here in the next few months.  But, we essentially had eight individuals in the lab and met with measurements over a 24-hour period.  So, we did pharmacokinetics analysis with theacrine at two different dosages relatively low and high, and then caffeine alone at a moderate dosage, and then the theacrine coupled with the caffeine.

We tried to determine, again, in that study what the half-life would be, what the max concentration would be alone and in isolation, as well as in combination.  What we see is that, in all individuals, it seems to behave in a pretty similar manner.  And interestingly, the caffeine addition seems to prolong the overall effect of the theacrine.  I think that's of interest to a lot of individuals who tend to use the theacrine nowadays within these blended dietary supplements that might contain caffeine.

Sometimes a lot of other ingredients that maybe we're really not so certain as to how they're behaving, but just the simple combination of a relatively low-dose caffeine.  In our study, we used 150 milligrams, so about the equivalent of a pretty cup of coffee coupled with the theacrine seem to have a really favorable effect on these individuals in terms of how they feel, etcetera, and it did seem to prolong the overall time course of theacrine in terms of concentration.  I think that's of interest, and once that paper comes out, people will be able to see the details in terms of the half-life as well as the peak concentration of the different dosages.

Jesse: Does the method of action within the brain seem to be similar on caffeine?  I know supplanting adenosine and not letting your brain become aware that you've sort of got this amounting of sleep pressure.  Is theacrine doing something similar?

Richard: That's a great question.  We haven't studied that.  This whole area, at least, from a human perspective is, what we would probably say, in its infancy in terms of study because there's only handful of published papers that have been done and none of them who really look at mechanism of action, per se.  I think our PK study that we just completed is probably one of the more sophisticated pieces work, but certainly a whole lot more needs to be done in this area.  Some of the animal works suggests specifically working on adenosine receptors and dopamine receptors, which may allow for the theacrine to have that dual phase or dual component effect.  But, admittedly, we really haven't really studied, from a mechanistic point of view, how exactly it's working, at least in humans, at this point.

Jesse: Is that something that's been studied in animals where there might be close parallels?

Richard: We haven't used it in animal models, but readers can look at PubMed and you’ll see a number of papers that are focused on the theacrine in animals, and there are some really interesting findings.  I mean, for me, personally, because we do a lot of work with oxidative stress and antioxidant capacity, it has been shown to be a very potent antioxidant and anti-inflammatory agent, and I think when we look at human disease as a whole, it appears that oxidative stress and inflammation seem to be one of the main players for just about every disease we're aware of from metabolic to cardiovascular to neurological.

I think that's interesting.  Now, that said, the dosages, oftentimes, that are used in these animal trials are very much higher than we would see in a typical human subject.  We've been using dosages anywhere from 25 milligrams up to a couple of hundred milligrams, and I think there's the paper using 300 milligrams of theacrine as well.

Actually, I just looked at a paper the other day, very interesting.  It was in mice, and it showed that, through oral administration of theacrine, it actually reduced liver damage that was induced through specific restrained stress on these animals.  I thought that was a great finding, but when you look at the dosing, the dosage was, I believe, 10 to 30 milligram per kilogram.  They dosed over one week.  I think it was a seven-day dose period.

One thing, whether it’s theacrine-specific or otherwise, I'd always caution listeners to focus on is when you look at this animal data, how relevant are they to humans based on the dose?  Because, if they're using 100 times what the effective dose would be in humans, you have to question how is that actually going to work from using a dosage that's significantly different.  That's very, very common to the dietary supplement world.

Jesse: That phrase, the dose makes the medicine, the does makes the poison is always worth coming back to.

Richard: Right.

Jesse: Is this a threat to the entrenched beverage industry, or are the ways that theacrine seems to avail itself in nature not something that you'd necessarily want to taste in their natural form so much.  Like, are there equivalents to coffee or tea that somebody might actually want to drink?

Richard: A good question.  As I mentioned, it's found in quantities that are pretty reasonable from at least the literature.  A cup of this particular Chinese Ku Cha tea, this K-U-C-H-A tea contains roughly the amount of 50 to 75 milligrams per cup.  A couple of cups of that tea would actually allow for a dosage that's pretty similar to what we've been delivering.

How that tastes, Jesse, I'm not sure, because I have heard from colleagues that embedding the theacrine into a beverage has been a challenge.  Obviously, if people are going to consume something on a regular basis, it needs to taste pretty decent.  I haven't consumed it in a liquid form in the past, so I'm not certain about that.  I've been in the mentality that I'm willing to try different things even if the flavor is not fantastic, but I think the average consumer, if it's not going to taste decent, time and time again, they're probably not going to consume it.  It's much better to dump that stuff, if possible, into a capsule and get it into the gut that way.

Jesse: One of the interesting, I'm not sure if this can be called a finding yet, but at least areas of research in theacrine sounds like it might not have the same tolerance that caffeine -- you build up a tolerance pretty quickly.  Can you talk a little about that?

Richard: Yes, that's a great point.  We haven't done any long-term treatments studies, but the group that did that work that you're referring to, and looking at that paper, the authors did suggest that.  I think that is very interesting because, as you know, not just even with caffeine, but frankly with a number of different things.  Years ago, when people use the ephedrine, you'd see the same thing.  They'd start with a 20 or 25 milligram caplet, and quickly, they're up to three or four of those caplets to get the same overall effect.

I know, for a lot of people, primarily from a cardiovascular perspective, a blood pressure perspective, that was concerning.  Now, again, there hasn't been multiple studies conducted to replicate these findings, but from the initial work, it does appear that it does not have the same sort of tolerance developed as you would see with something like caffeine, where people need more and more they get the same overall effect.  I think that is an interesting overall finding, but we also need studies to replicate that and across different populations of individuals from men to women to any potential user, old and young.

Jesse: Have you seen any interesting or scary adversary actions, things that people should be aware of?

Richard: That's another great question because with this particular class of dietary supplements, if you lump it into the typical stimulant or class of supplement that are targeting focus, etcetera, generally that's been a concern, but we've personally done measurements primarily of blood pressure with treatment.  In this PK study, we did 24-hour assessment of these individuals and heart rate.  In other studies, we've done the same.  We see a negligible increase, if any.  In fact, some of these values have actually decreased across time.  But, from blood pressure perspective, the most we're seeing is about a two to three millimeter of mercury bump with acute treatment, which is obviously small.  I know the studies that have actually done some blood measurements, metabolic annals, and things like that, they haven't noted anything of significance either.

I think that's interesting, because, again, so many individuals are using products or wanting, desiring products that could yield the sort of benefits that the theacrine has been shown to yield.  But, they are concerned about, oftentimes, "Does this elevate my blood pressure.  Is it causing any sort of adverse cardiovascular effect?" At least, to date, we haven't seen that.  We haven't had any individuals that have any sort of adverse reactions to treatment.

Jesse: One of the things that I've come across in talking with people about caffeine is, every now and then, it seems like there's a sliver of the population that almost has an inverted reaction to caffeine than what you would expect where it makes them drowsy or sleepy as opposed to pepping them up.  Have you seen anything paralleling that with theacrine?

Richard: We haven't to date.  That said, when you say we've measured individuals, we're talking, maybe over the course of our studies, we've assessed 100 individuals.  Usually, I think if you'd want hundreds or thousands of individuals, and obviously companies that are selling products containing these things, they may have additional data that they're collecting.  But, from a scientific controlled experiment perspective, we have a relatively small sample, I think, of individuals.

But, that said, we haven't noticed individuals having that sort of reaction.  Most individuals having that sort of reaction.  Most individuals do tend to feel that their focus is enhanced, that their energy concentration, overall mood, is enhanced.  But, again, like anything else, it varies.  Some people are claiming dramatic effects, and other individuals are claiming that, "Well, I might feel a little bit better, but I'm really not sure." I think that's something that we see with all dietary supplements and variability and response.

Jesse: I was seeing in some of the studies, it sounded as if there was a bit a dose response inversion where small but measurable doses, it was actually calming for some people, but then after a certain threshold, it would start having the more caffeine-like stimulatory effects.

Richard: Yeah, I've read the same.  We, in our lab, haven't done that work.  Now, we have used a couple of different dosages.  In one of our recent studies, we used a low-end dose of 25 milligrams, then a high-end dose of 125 milligrams, so essentially five times the amount.  But, we didn't see any, as you're describing, major changes in terms of calming versus stimulants.  I know the other group has commented on that.  They have used dosages, I think, the upwards of 300 or 400 milligrams of theacrine.

But, our sample size, frankly, I think has been too small in our work, to date, at least to show there's some differences in terms of the calming effect versus the stimulatory effects.  In some individuals, certainly, that's the case, but I think we always want to use caution if our sample's so small that, statistically, we're not able to really detect anything.  I think there's possibilities for that, and further work with larger sample sizes may actually show exactly what you're describing.

Jesse: If somebody's curious and wants to try theacrine in its purer form as, I guess, they can get it on the market nowadays where it's not necessarily mixed with too many different things, what is their best route for being able to take that N=1 experiment?

Richard: Well, again, that's something they probably get to do a little bit of digging on.  I know there's a lot of products out there that are containing the theacrine, but most of them contain, in conjunction with it, at the minimum caffeine.  In many cases, it's going to be caffeine coupled with multiple other ingredients that really may or may not be having an impact.  Purchasing the raw material and then actually dumping it into a beverage or something like that, that might be difficult, if they're even able to obtain the raw material as an individual versus a research group or university.  I think, probably, their best bet would be to search some of these online sources and see if they can get simply theacrine encapsulated at dosages of 1,500 milligrams, then they can experiment with a relatively low dose to start, and potentially move up.

Jesse: Are there any people that you would recommend that don't try theacrine - pregnant women or children under a certain age, people that should just stay clear of it?

Richard: I think, probably, we'd use the same cautious recommendation that we'd have with most other things: individuals who are, obviously, pregnant, nursing, younger individuals, individuals with known cardiovascular disease.  That said, some might argue that, "Well, if it’s an antioxidant, anti-inflammatory, and it may actually stimulate mood, and it has no adverse impact on heart rate and blood pressure, why would that be a concern?"

Well, again, I can use the typical disclaimer of, "Consult your physician or medical professional before using it," but I think, obviously, people need to be cautious and do their research upfront, find out what they're using, make certain that the product they're using they trust, because we both know that sometimes even with the CGMPs, etcetera, you want to make certain that what you're using and what you think is in that capsule is actually in that capsule.  So, trusted sources, talking to some people who seem to know a bit about this particular ingredient or product, I think, would be wise before starting ingest things that they're not aware of.

I think, in general, if you look across the studies, and you're obviously aware of this, and your listeners probably are too, we generally see, with the theacrine, especially when it's coupled with a moderate dose of caffeine, improvements in overall focus, improvements in subjective feelings, energy, and vigor, vitality, things of that sort.  A lot of times, these products are marketed for sport performance, etcetera, and that's fine.

But, I think the reality is when you look at so many other products on the market that are targeting people that just want to feel a little bit better during the day, that market is quite large, and I think a lot of individuals, whether you're physically active or you're mentally active on the job, at home, whatever it may be, potentially could benefit from something like this.  So, it's something I think that, in conjunction with a great diet, in conjunction with physical activity, regular exercise, hopefully people are doing those things, because those are the most important things, adding something like this to their regimen on an irregular basis, or a few days a week basis, might be something to consider.