Exploring the mechanisms and effects of Curranz - Dr Sam Shepherd

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Welcome, hi, I'm Mikki and this is Mikkipedia, where I sit down and chat to doctors, professors, athletes, practitioners, and experts in their fields related to health, nutrition, fitness, and wellbeing, and I'm delighted that you're here.

Hey everyone, it's Micki here. You're listening to Mikkipedia. And this week on the podcast, I speak to Dr. Sam Sheppard. He is a senior lecturer in exercise and sports nutrition at Liverpool John Moores University. And we talk all about uncovering the mechanisms behind the Curranz supplement. So Sam is a lead researcher in that field. And while I have spoken a couple of times to Fleur Cushman,

who is the director of Health Currency Limited, which is the company behind the current supplement, I really wanted to talk to those who are at the coalface, who are in the lab analysing the data and seeing those real results. So Sam and I spoke about both performance and health applications of the supplement, the mechanisms behind it, and how Sam sees the potential for athletes and general population alike. And what I found really interesting,

with this discussion is just how Sam really came at it with a sceptical science mind, which is, as real scientists would tell you, how you should always approach a topic. And now that he's done a ton of research in the area and he's also witnessed results being replicated in other labs, he's really excited for the future work to be conducted to understand further how this supplement can help. And that is of course both.

for athletes and the general population. Now you will see as we sort of come into the conversation that Sam and I were just sort of already talking and we just sort of left that little bit in. In addition to the Curranz supplement research, Sam and I also talk about his work with a wider research group all about the concept of fuelling for the work required and how research looking at

what we know in that space over time. So it is a wide-reaching conversation and I think you're really going to enjoy it regardless of whether or not you're an athlete. So Dr. Sam Shepard, senior lecturer in sport and exercise nutrition, is an academic staff member with teaching duties at Liverpool John Moore University. Sam's research aims to develop exercise and or nutritional strategies to.

improved cardio metabolic health and insulin sensitivity in at risk populations such as those with metabolic syndrome, type 1 and type 2 diabetes and just that natural process of aging. But he also is interested in maximizing the metabolic adaptations to acute and chronic exercise training. Contributing to achieving these aims is a large body of work that focuses on understanding the molecular regulation of skeletal muscle lipid metabolism.

Sam is also an expert in the use of immunofluorescence microscopy and transmission electronic microscopy methods which are integral to previous and ongoing research studies. And Sam and I actually talk about this but not in a very geeky nerdy way that you have to particularly understand but I was super interested in that because it involves mitochondria and that's a real buzzword right now.

What I would also say is that Curranz have come to the party for this podcast and for first time purchasers, you have the opportunity to get yourself started with 25% off that initial purchase of their Curranz supplement. And that is using the code, Mickey, that's my name. Pretty easy right? And the link is over on the show notes or go direct to their website, www.currens.co.nz.

And before we crack on into the interview, I'd just like to remind you that the best way to support the podcast is to hit the subscribe button on your favourite podcast listening platform. That increases the visibility of the podcast out there and it makes literally thousands of other podcasts so more people get the opportunity to learn from the guests that I have on the show. All right, team, please enjoy this conversation that I have with Dr. Sam Sheppard.

and it begins getting light, or at least where we were, like 4.30, like super early. Yeah, it's lovely at the moment. I mean, like this morning, we was out, you know, going, doing laps of the park on the bike, but it's sort of like half five in the morning, it's just nice and quiet, but lovely weather. Nice. Yeah, it's lovely at the moment. While it lasts anyway, at least this weather, while it lasts. Oh, 100%, right. And Sam, are you like an athlete yourself? Yeah, so I do triathlon.

Ironman mainly. The long stuff interests me the most for many reasons. Yeah so that's typically where I'm at really. Yeah cool. I did Ironman Lanzarote yeah two or three weeks what was it three weeks ago four weeks ago now. It was the last one so yeah we were pretty lucky actually with the weather. Have you been to Lanzarote? No not yet. No I mean Canary, the Canary Islands so they're typically windy.

I've been there a few times and done training camps and on race day, it wasn't too windy. It was breezy, let's say, which is acceptable for Lanzelotti. The temperature was early 20s, mid 20s by the end of the day or the afternoon when you're running. So we were pretty lucky really. It was a quick day. I think the course record was broken actually by the pro. Oh, amazing. We won it, yeah.

Although Sam Laidlaw was winning at one point and he pulled up. Yeah. We should GI issues or something. But yeah, so that's my, that's my bag really. I'm and yeah, like I say, it's application of knowledge, isn't it? And that sort of idea. I was going to ask you that actually, because of course you've done a heap of work in the sort of carbohydrate fuel utilization space as well. Have you sort of like taken those principles and applied them to yourself? Yeah. So I suppose.

A lot of that work, and I know you wanted to talk about it, which I'm sort of happy to, but I was certainly on the periphery, at least in terms of study, design and things. James and Sam led that work and Mark Keiris more recently and Kelly Hammond. But yeah, so I was kind of like a supporting role, but I've got involved in probably a little bit more in the last few years with James and doing a bit more of that work. But yeah, it certainly helps to, you know, you take those principles a lot and apply them to yourselves. I mean...

We also kind of had a, as everyone did during COVID, you sort of go, oh God, what's going on with my life and things like this. And then me and a girl I work with, we set up like a nutrition consultancy business, which is nice because that allows the sort of application of that knowledge, which was, I think sometimes, I don't know, in academia, you do the studies, but you never really see the end user. And certainly,

trying to do some consultancy work as I have the last three years now, it's a nice way to use that knowledge and apply it and actually see the results of it. Yeah. Rather than do a study and hope it works in the real world for some people who you never are gonna meet. So yeah, it's quite nice to be able to do that as well as the kind of academic stuff. I agree. And I spoke to a colleague of yours, Brendan Egan.

he was saying the same thing is that, you know, he, he works in the sort of exercise aging ketone type space. And he, and, but also on the side of that, he was also a consultant. And so he could, he saw sort of from what the, the research of the literature was saying about exogenous ketones, getting these quite different reports from the people that he was, he was talking to, which is, you know, super interesting.

sort of periodization and the fuel for the work required. I certainly set out initially with, oh, this will work for everyone. And no, it's so individual and also, you know, work with a lot of sort of age group athletes and it's how you bring it into their daily lives when they've got work and other family stresses and things like that. Sometimes it's not possible, for some it is, and they see, potentially see the benefits of it. But it's, yes, very individual whereas.

you read a paper, you think, oh, that'll work in everyone and job done. I know. Do you find Sam as well, that is, is there a difference for you with regards to working with your elite, um, athletes versus the age group? Like, cause in my experience, the elite seem to be able to handle more carbohydrate, go super hard, have less of those GI issues. And then when you are working with someone who, who is as not as serious, maybe, you know, but they're very serious about the sport, but.

It's just a different, it feels like a different playing field when it comes to the nutrition piece. Yeah, I think that's fair to say. I mean, we work with a lot of age group athletes where you say to them, oh, how many, you know, how much, there was a classic example this week actually. I started working, it's all right, you need to fuel that sort of 90 to 100 grams of cars per hour for this ride. You know, three or four hour ride he was doing at the weekend in a sort of prep session and he was like, came back, he's like, I've had one pack of shit, Cliff shot blocks per hour. Is that about right? And you're like...

No. Yeah. What we've done previously, and he's like, well, I used to do that in 70.3, but I really used to struggle on the run. And you're like, well, yeah, you fuel in about 50 grams of carbs an hour. I'm not surprised you like that. Yes. Absolutely died on the run. Yeah. So it's more that, and then the top end guys tend to know that and have been working at that. And it's just tweaks here and there, really for those people. Yeah. Or at least in triathlon, that seems to be the case anyway, I think.

Most people are quite aware of the guidelines, I suppose, and then it's just figuring that out relative to the races that they're doing and how they're going to carry it, for example, and things like that. And around those sorts of challenges is the main sort of thing for those guys. But they can certainly tolerate more. And they're also happier to do it in the training, whereas I think the age groupers are a bit like, yeah, well, firstly, it's the cost of a lot of this sort of stuff, which is one issue.

Um, but also they, a lot of them come with the idea that I want to lose a bit of weight and you're like, okay, but if you feel you're training appropriately, then you will, because you're not going to wake me later in the day or something like that. Um, so I think that that's the main challenge for those, for those guys. Yeah. And, um, Sam, how did Lensorotti go? Uh, yeah, good. Um, uh, what was that? Tenth overall. So yeah, good job. Yeah. So, um.

It's crazy the strength of the age group fields in general though. I mean, yeah, what was I like fifth in my age group, but yeah, tenth overall. I think we worked out the top 10 would have finished top 15, you know, within the top 15 in the pro race. It's just like the, it's just crazy that the standard, you know, maybe you train like 15, 16 hours a week and you think, how can I possibly do anymore or what, you know, what kind of.

How do you move this on in terms of those results? But you just have to accept that there's a lot of people who are probably working part time and training the rest of the time. And particularly in triathlon, I think it's, you know, it's sort of affluent sport, isn't it? In terms of finance, you get a lot of people, particularly older people, actually, who've retired, maybe retired early and they're just, they're just training for 25 hours a week. And you're like, well, you can't compete with that. So, no, and, you know, a lot of my clients have sort of at that, um,

like mid-thirties, late thirties, maybe early forties, they've got a family, they've sort of built, established themselves within their career. And now they're like, I just want another challenge. And they've got the resources behind them and in some instances, that flexibility of time to be able to spend those hours, you know, really killing it actually. Yeah, yeah, yeah. It's, yeah, it's crazy. You just, you can get really...

sort of downbeat by it, I think sometimes. If you think, I've put in all this effort and I'm just not really seeing the result, but you've got to remember it's a hobby today as well. I'm doing it for fun. That's why I always have to remind myself when it's tough in races, you think, actually, I've chosen to do this. Yeah. When you're deep into a marathon, you're still questioning yourself, but you're trying to tell yourself. You just have to bring the Dave Goggins, Sam.

Yeah, yeah, and then you're like, sweet. Yeah. So Sam, can we, can you give us a bit of your background? So how did you get involved in sports nutrition and your, your, yeah, your sort of interests in this sort of research space? Yeah, so I suppose, oh God, I probably thought, I thought about this a little bit. And I thought about this a little bit in the last few years, actually, when we've been setting up to endure its nutrition, because

thought actually, I look back and when I was at school, I really wanted to get into sports nutrition and I remember when I finished GCSEs and we had like a school assembly and they said, oh, what do you want to do? And we kind of went round and I was like, oh, I want to be a nutritionist. And I really like PE, so you sort of, you know, that's the thing that you want to do. And it's sort of, yeah, weirdly in the last few years, it's become true, which is quite nice.

But yeah, so, you know, the usual undergraduate degree in sports, sport and exercise science, I went to, so I did that at University of Birmingham, did a masters at Aberdeen, which was more human nutrition and metabolism, which I think was great because it wasn't so specific to sports nutrition. So it gave me a good overview of nutrition, but also from a health perspective largely. So that was at the Rowatt Research Institute up in Aberdeen. And then I went back to the University of Birmingham.

to do a PhD with Anton Wagamakas. And that was focusing on really exercise training and particularly high intensity interval training, which was quite, I suppose, a hot topic at that time. And we were interested in how that could be used to improve insulin sensitivity and reduce the risk of type 2 diabetes in sort of ultimately in overweight or obese individuals. And I was coming at it from

more of how can we, or what effect is high intensity interval training having on substrate metabolism. So I've got probably my main focus on lipid metabolism, fat metabolism, essentially. And so, you know, the relationship between fat metabolism and health and insulin sensitivity in particular was where I was at. And so, yeah, I did that, did my PhD and then a kind of postdoc for about a year, which was trying to...

take high intensity interval training a bit more mainstream, let's say. So we, you know, we, it works in the lab, but we want to see how it works in a more real world setting, which we kind of did a nice study with about 90 people doing a high intensity interval training program over sort of a, yeah, it took about 12 months to do that. And then after that moved to Liverpool John Moores University in 2012 to take up a lecturing role there and then, yeah, I've just continued.

I suppose continued that sort of high intensity internal training related work and health in the first instance. And then as I've started working with people like James Moreton and Graham Close at Liverpool John Walls University sort of gone down a little bit more of a nutrition pathway. But ultimately, I think, you know, if I describe my research, I'm interested in substrate metabolism, so fat and carbohydrate metabolism and how we can probably manipulate, well, firstly, understand the mechanisms of that.

but also how we can manipulate that to either improve health or maybe enhance the adaptations training and therefore improve performance essentially. So yeah, that's kind of me in a nutshell. Yeah, and Sam, what was sort of the major outcomes of your earlier research, which you obviously, you sort of like, you've progressed that over the last 10 years, but with your PhD and particularly your postdoc in that real world setting. Yeah, so.

It was a time, I remember we had a sort of seminar when I started my PhD in fact, from Martin Gabala who was of course at McMaster and he led a lot of that research in high intensity interval training at the time with Kirsten Bergermaster and we were really interested in how that could be adopted from a health perspective because of the sort of time efficient nature of that type of training. And so I worked with one of my colleagues who's also at

Liverpool John Walls University now, Matt Cox, and he was interested in the kind of improvements in sort of cardiovascular related outcomes, so endothelial function and things like that. I was more interested in how high intensity interval training would drive adaptations in muscle related to substrate metabolism. And ultimately we showed that it could improve fat oxidation to a similar or to a similar extent.

particularly the use of the fat that's in the muscle, so the intramuscular triglycerides, to the same extent as more traditional endurance training. So that was quite nice, quite unexpected in many ways. And that meant that, well, the theory was that if you're increasing the capacity to use the fat within the muscle, that would potentially lead to an improvement in insulin sensitivity because we know that if you accumulate fat in muscle...

particularly if you're sedentary, you don't do much exercise and that can be quite harmful to metabolic health essentially. So that's, yeah, so we kind of proved that, let's say, in sort of lean sedentary individuals in the first instance and we repeated that in an obese cohort. And that was my PhD work. And then we said, right, it works in the lab. Ultimately, the next step is to take this out into the, let's say, the real world. So we set up a...

basically similar to a spin class in many ways that we, we use the spin bikes. In fact, at the Leica centre that was on site at the university of Birmingham. And basically we had one group doing endurance type training in on the spin bikes, and then another group doing high intensity into full training. And again, we just looked at some very basic sort of cardio metabolic outcomes. So insulin sensitivity changes in VO two max and things like that really. And again, showed that you could get similar.

benefits in terms of those cardio metabolic outcomes as you did with this sort of more typical endurance training. But the nice thing was that more, you know, when we looked at some of the psychological aspects, let's say, and motivation, I didn't leave that because that's not my expertise. So you collaborate with someone else. But we were, you know, we saw that you kind of, you're more motivated to do that type of exercise. People engage more with it. They adhered more to it. So that was quite a nice outcome really.

to essentially progress that work when I moved to Liverpool John Moores. Yeah. And is it because it's shorter that people are more likely to adhere to it? What did a hit session look like compared to say your standard endurance? Yeah. So in the lab, they are very, I will call them extreme in many ways, that you're doing, it's the Wingate type, 30 seconds of all that effort.

four and a half minutes rest and repeat that several times. And when we took that, we kind of softened that a little bit as we took it into the real world, if we like, where it might be sort of a minute, minute on minute off tile of high intensity and full training. And it was, it's all very self-selected, of course, in terms of effort. And you were just asking people to raise their heart rate to maybe 80 to 90% of their sort of max.

or working on how out of breath do you feel. So you're trying to make it a bit more in terms of a feeling, I would say. And that's what we've tried to do in the real world. And there's my colleague, Matt Cox, he's done a lot more work in more recent years on how that can be applied in more clinical settings. So we actually did some work in type one diabetes patients when we first moved to Liverpool, John Moores University and that was quite nice.

showing that the high-intensity interval training could kind of get rid of the hypoglycaemic effects of more moderate-intensity exercise. And that's why a lot of people who are type 1 diabetic might not like exercising because if you just walk at a moderate pace or run at a moderate pace, then you get a decline in your blood glucose essentially in those people. Whereas the high-intensity interval training, you stimulate glucose production by the liver because you're getting greater increases in adrenaline.

and then you're sort of in a safer zone from a glycemia perspective. But he's also taking that on now and doing some work in a number of different clinical populations, even in some sort of more paediatric sort of stuff as well. But yeah, it was an interesting time, let's say. Yeah. But I suppose the main reason people tend to prefer that is

that it's over quite quickly. Yes. Yeah. And a little bit more enjoyable than the monotony, I suppose, of the sort of more moderate intensity exercise, which is quite amusing because I quite like the monotonous stuff. Yeah, I know. I don't know that I can't. That's the thing, right? I'm an endurance athlete as well, and that sort of long and steady, like that really sort of hits a sweet spot for me, but.

I do. And also, like I'm thinking as you're talking about that sort of harder effort, it is hard at the time, but you do like, you do just feel like a little bit like you get a bit of a buzz and a bit invigorated when you do it too, I suppose. Absolutely. Yeah, absolutely. I mean, yeah, we still can't get away with just plodding around, can we?

Unfortunately. So Sam, it's interesting, you know, obviously you're interested in that insulin sensitivity piece because of course you've done a lot of work with the New Zealand Black Currant supplement currants and a lot of, as I understand it, there is research that sort of aligns with your initial sort of research space. Would that like, in terms of the health benefits of taking a supplement like that? Yeah. So I suppose.

That was one of the reasons we were, well, one of probably two reasons why we were initially interested in this supplement. So I should say, first of all, that the reason I kind of got into, or my interest in Curranz arose was through Mark Williams, who is based at University of Chichester, and he's led a lot of this work. You know, he's done much more work on this than me, to be honest. But he actually approached us.

He'd done a study with Matthew Cook, who was his PhD student at the time, and they showed that you could improve fat oxidation, fat burning capacity in layman's terms, with short-term supplementation with the New Zealand black currant extract supplement. And so he approached us because they'd done this work in healthy males and showed you

I think they were struggling to recruit females in Chichester, and I was semi-confident we could recruit some in Liverpool. So I thought on that challenge, I'd say. So yeah, we did this study up at LJMU, basically replicating one of the studies that Matt Cooke had done in males, and just were also interested if the effect continued into females as well. So that was kind of one aspect. And then...

from that we've developed this in, you start reading the papers in this area and you go, okay, so there might be some potential benefits to insulin sensitivity here as well. There might be some sort of more health, well, I suppose the fat metabolism is health as well, but also, you know, sort of more metabolic health related effects that we might be able to see with this blackcurrant extract as well. Yeah, and...

Can we, like Sam, I've had Fleur on the show a couple of times, actually, which is brilliant, because she's obviously, as sort of co-founder of Curranz, she's very knowledgeable about the mechanisms of which it works. Can you remind us of some of the mechanisms which would make Curranz this urkogenic aid? Yeah, so I think for me, in terms of its erogenicity,

I think one of the things to say straight away is that, let's be clear that, you know, it's essentially a polyphenolic compound. Yeah. It's found in, you know, fruit and vegetables essentially, and as all polyphenolic compounds pretty much are. And so if you have a higher intake of fruit and vegetables, then there's definitely a, you know, that's great for health, let's say. And we know that full well. The New Zealand black currant.

extract is quite interesting because it's, well you've got polyphenols kind of at one level and then that splits off and you've got flavonoids and it's a flavonoid subclass, so you've also got other flavonoids like catechins for example that you find in green tea or something like that. What you, in terms of its sort of ergogenic effect, it largely seems to stem from its sort of anti-inflammatory or antioxidant sort of capacity of the black grunts themselves.

That's part of the mechanism. And when we kind of look in the literature and there's sort of the cell work, where there's been a lot of efforts to try and understand the mechanisms by which anthocyanins themselves might work and specific anthocyanins. In those cases, the raw product.

has been applied to cells and then we see things like an increase in glucose transporter expression. So we think, oh, it might be able to support glucose uptake into cells. Or one of the other things that we see is it increases the expression of endothelial nitric oxide synthase. And so that's important for the production of nitric oxide. So we also think it might be important in regulating blood flow and that might be one of the mechanisms.

I don't really think we know the precise mechanisms by which the extract itself will work. We have an idea from some of the cell work and I guess this is what we're trying to do at Liverpool John Walls University now and have been for the last few years is look at what the benefits are but ultimately answer why. We see some of those benefits as well. Yeah because I guess when you're doing like a petri dish

type study, you're looking at cells in isolation from the entire like organism, if you like. And so, and things don't generally work in isolation. Is that, would that be how you sort of see it? Yeah. I mean, so there's, there's that one aspect of it, but one of the things we, we, well, I suppose anthocyanins themselves are fairly, or their bioavailability is fairly low. So when you ingest anthocyanins, something like 12 to 15%.

what you see in the circulation and they peak after like one or two hours and then they're out again pretty quickly. So if you think about the ergogenic effect of that or potentially it's quite short-lived but we still see some benefits you know to fat metabolism or insulin sensitivity or recovery from exercise or whatever it is and so what we think is happening is that the anthocyanins are metabolized themselves in in the body and

you can measure those metabolites in the blood plasma or serum and they remain sort of elevated for sort of 24 to 48 hours. So it's and again, what we believe is that it's these metabolites that are having the sort of purported beneficial effects within the within the, you know, within the body itself. So going back to the kind of cell work that people have done previously.

It's been great because it suggests that these antisinins might have, you know, benefits and gives you an idea in terms of the mechanisms by which they may work. What we're starting to do at Liverpool John Moores University, so I've just got a PhD student starting on this, is basically rather than applying the raw product to a cell in a dish, like we say, we're going to provide people with the extract, take blood.

for sort of six hours afterwards, periodically, and then separate the serum and then apply that serum to the cells. So you're getting the metabolites, you're exposing cells to the metabolites and then you can look at those mechanisms but actually a little bit more closely aligned to what the tissue in vivo would actually see. Yeah.

be exposed to. So that's the idea of some of the work that we're just actually started in the last few months at Liverpool. Nice. And Sam, what was the outcome of your female specific study with fat oxidation? Yeah, so I was, I'll be honest, I was a bit sceptical when we first did it, which is nice. I think that's probably the best way to be a lot of the time. And so, as I said, we sort of spoke to Mark about it and we're like, right, we'll go for it.

What we saw was we saw an increase or an improvement in fat oxidation, essentially, in the females. So they did two hours of prolonged exercise, just moderate intensity exercise, sort of 65% of BO2 max. And we measured whole body rates of fat oxidation during that two hour period. And they did it following a placebo supplementation period of seven days or a black run extract supplementation period of seven days. And it was the...

I think about a 27% increase in fat oxidation following the black or comparing the black currant to the placebo condition, which was, yeah, I was quite surprised to see. Yeah. Yeah. Is it clinically meaningful? I think this is where it becomes tricky. I suppose what I was interested in initially is that that was, I think, almost exactly the same as...

one of the studies from Matt Cook, where they showed an increase in fat oxygen. I think one of them also reported a 27% increase. I know there was another one that I think was like a 22 or 23% increase as well. So we're getting, you know, in the realms of, you know, we're repeating this in different labs and seeing the same sort of thing, which is nice. If I compare that to some, you know, exercise training studies,

It's difficult, you can cherry pick a little bit here, but I don't know, if I think back to my PhD and some of the ones that I looked at in more detail, some of the sort of highly cited ones, three months of sort of low intensity, moderate exercise in sedentary individuals and that increased vaccination by about 35%. It's not too far away from that. So I think it's meaningful in that regard.

in that we're able to elicit similar, or surprisingly I suppose, elicit similar increases in whole body rates of fat oxidation compared to some sort of more, you know, typical training studies that we might do, endurance training studies, which is, yeah, pretty, I think, pretty interesting. Yeah. I think it's also important to look, and that's the relative change of course that we're interested in there, but I think it's also important to consider the absolute change.

And that's fairly moderate, I would say. And, but that being said, and one of the things that we're, I suppose we want to do now is like, how meaningful is that change? And to go back to your original question, and I think for me, it's like, if we are improving our ability to burn fat, then hopefully from a performance perspective, we're suppressing, or sorry, reducing glycogen utilization.

carbohydrate oxidation and therefore if we can do that and that small or moderate increase in fat oxidation is sparing glycogen then ultimately we should be able to improve performance and that's actually one of the studies where we're just finalizing the results for at the moment. So again that was the PhD student who's just started now with us, Lawrence, that was his sort of master's project.

We did that in males rather than females, I should say. We were very controlled, a lot of dietary control to ensure we started with the same levels of muscle glycogen. We did depletions before and things like that to really normalize glycogen. Again, we saw, I think this time, a 24% increase in whole body fat oxidation. So again, you know, within what we've seen before. And one of the things we're doing at the moment is doing the glycogen analysis, because after the two hours of

prolonged exercise. In this latest study, we just did an exercise capacity test. So basically, you cycle for as long as you can at 150% of lactate threshold. It's fairly short, but it's ultimately dependent on muscle glycogen levels. And I think it was something like of the, I want to say 11 participants, I think nine of them improved their performance with the currents. So I can't remember the exact numbers in terms of what that was.

But that suggests that, or to me at least, that there might be some sparing effect on glycogen there. But yeah, I suppose all I can say is watch this space because we're kind of finalizing that analysis at the moment. But I think that potentially, in terms of performance, could be one of the benefits for the current supplement. Yeah. And Sam, were these in, it sounded like the female cohort was an untrained cohort, is that?

Yeah, probably we had a bit of a range. There were some cyclists in there but then some people who were, let's call them, I wouldn't say sedentary, more physically active. They were still exercising and they were accustomed to endurance exercise but they weren't serious cyclists let's say. So a bit of a range in that respect. I think it's worth saying that

Certainly Mark Williams at Chichester over the last few years has done some of this work in, yeah, certainly sedentary individual, males and females. And again, they show that there's improvements in fat metabolism during walking in those people. So even across that sort of spectrum of physical activity, we're seeing similar benefits to fat metabolism at least. Yeah. And do we think then Sam,

If I'm thinking about your triathlete or ultra-runner who is well trained, are we thinking that it would still be an additive effect or do we just not know that yet? What's your gut feel on that? Yeah, so I don't think we really know that yet. Again, I'll refer to one of the papers recently from Mark Williams. So they did a case study and they took an ultra-runner.

They did basically seven days of currant supplementation and they looked at substrate use before and after that period. So no placebo condition in this case. And this was an N of one, of course, as it's a case study, but they did see improvements in fat metabolism just with the seven days of currant. So I think there's more work to be done in that space for sure. And whether those benefits are realized to the same extent, if at all, in the sort of, yeah.

higher end athletes, let's say, compared to you, sort of moderately trained people that you're doing this work in. Yeah, and I mean, anecdotally, I know a lot of people take it and a lot of people love it as well, and I take it also. Sam, what dose was used in the studies? What is that sort of suggested dose? Yeah, so the studies we've done, again, is a lot based on what Mark's done,

600mg which is basically 210mg of anthocyanins daily. Again another study from Mark led by Matt Cook, they did a dose response study so they compared placebo to 300, 600 or 900mg capsules. I should say that that's just over 100, just over 200 and just over 300mg of anthocyanins which is the active bit.

and they didn't see an increase from six to 900. So 600 milligrams is typically what, at least for fat metabolism as the outcome, is what we sort of aim at based on that work. Yeah, and is there utility, Sam, in taking repeated doses of the current supplement throughout a really long session?

That's something that I think we need to look at in a little bit more detail. So I've talked to Fleur about this a little bit in the past because we actually supported a guy last year doing a deca, for example, and we got him to take the, because he was out there 14, 15 hours every day, we made sure that he was taking that periodically through the day. I think it was every six hours in the end we were looking at.

just to try and maintain the metabolites to a greater extent. I think one of the things that we, if we think that the metabolites are having this beneficial effect, my assumption would be that exercise would increase the turnover of those metabolites. So, supplementing more regularly is probably.

in those longer sessions. So I'm thinking, you know, some of the ultra-endurance events where they go in, you know, eight, nine, 10 hours plus that we might need to start and start to supplement more than, you know, more than once essentially. But I think there's more work to be done in that space, or at least I'm not aware of studies that have really done that. Probably anecdotal evidence and Fleur shares some of that with me.

that's what we should be doing but it's like everything with this isn't it the science normally catches up and answers the question as to why people are doing these things in the first place. Yeah for sure and am I right in thinking there is a recovery element to black currents that has also been studied for sort of higher performance athletes? From a higher performance perspective yeah so there's a sort of few things.

I think a lot of, again, this is based on anecdotal data that people who've been taking it sort of suggest. So I know there's a lot of ultra-runners taking it, or like mountain, people doing mountain racing, mountain bike racing, certainly triathlon, things like that, where there's, you're putting a significant strain on the body essentially for a prolonged period of time. And there's some sort of anecdotal reports that the current helps to.

would help you with recovery there. One of the more, I suppose the research studies to kind of look at that was led by Julie Hunt and Ralph Mander, so they're at Surrey University in the UK. And they actually did a very basic study because we wanted to, I suppose they wanted to know essentially whether there really was this benefit to recovery. So one of the...

experimental models that you can do to test that is eccentric loading of a muscle and make it really localized. So they did. I think they were bicep curls or it might have even been forearm exercise. I can't remember off the top of my head now. But very localized damage that they were inducing with this eccentric exercise loading. And they showed that you could, with the current supplement, then you would improve recovery. So

sort of there was some subjective measures in there. So, you know, how saw on a visual analogue scale, but also some markers of recovery as well there. So they measured creatine kinase and we can probably argue there's some issues with creatine kinase, but the currents seem to all or allow sort of, or keep creatine kinase, circulating creatine kinase concentrations almost sort of a baseline level.

And you've got significant rises when you weren't taking it. So that's, I think, something that needs to be followed up in other sort of recovery based studies moving forward. But I think. Any, probably any sort of exercise where you are. Inducing sort of, yeah, or using eccentric loading and thinking things like even like fell running, you know, downhill running, if there's that aspect to it and.

even like cross country, sorry, just downhill skiing or something like that. CrossFit, I think is probably a big area as well, potentially. I think there could be a real utilisation of the currents there, as well as some of the, you know, at least based on the anecdotal evidence that we see from the ultra-runners or the triathletes or people from mountain boxing and fell running already, where they sort of support that.

recovery aspect as well. Yeah, nice. I think I saw a study looking at the neutrophil function in rowers that was a, that sort of suggested that after some high intense rowing exercise, to be fair, the rowing machine, what else would it be if it's rowing? I mean, it's always gonna be high intense and horrible and something everyone wants to avoid, or at least I do, want to avoid. But I believe there was that enhanced neutrophil sort of function. I don't have.

details in front of me though which might which may be a different mechanism or a something else with regards to the immune system that might be helpful maybe. Yeah I suppose we always talk about recovery and we think about recovery of muscle function but I think recovery covers many different aspects really and you pick and choose what you want to study in that respect so yeah the muscle function aspect is one but also you know we

We know that if you do very hard exercise, and particularly over a long period, then you get this kind of drop in circulating neutrophils. And that's what's leading to that immunosuppression. And I think it was a study from Roger Hirst in New Zealand at Plant & Food that you're referring to. And they showed that, yeah, after that rowing exercise, that you kind of maintained the neutrophils levels in circulation essentially. So in theory, you should be.

reducing your risk of any, or reducing your risk of picking up any sort of infections there. So, and I think that's an important aspect of recovery, but especially if we think of it in an applied perspective where you might have cyclists doing a week long tour, something like that. Even as basic as taking a group of age group triathletes on a training camp and they're increasing their training volume. Everyone probably doubles their training volume for that week.

And they come back absolutely obliterated back into work. But, you know, ultimately they're at greater risk of picking up something. And how many how many times you see people, you know, go on a training camp and pick up an infection on the way home or something like that, even from racing as well. So I think there's there's definitely application, at least based on the work that Roger's done there in terms of maintaining neutrophil function and levels with the currents.

then there's definitely application from a recovery perspective there as well. Yeah, nice. And of course, Sam, you know, we're all athletes in some way, shape or form, aren't we? So all of the performance benefits, I always often think, how is this going to be applied in that health setting? And of course, a lot of your earlier research and your continuing research is in that space as well. So are they the same mechanisms at work that could potentially help improve health outcomes as well?

And I guess this is one of the questions that we're trying to answer. Yeah. First of all, I guess we tried to say, well, does it improve insulin sensitivity? That was kind of the first study that we took in that space at Liverpool John Moores University. And I suppose that was ultimately based on the fact that, yes, we see some antioxidant and anti-inflammatory sort of effects of the...

the New Zealand black currant extract itself. And also some of the cell work that I talked about earlier, one of the outcomes that we've seen in that sort of work is that it can increase that nitric oxide synthase protein. And that's important for improving blood flow. And if we improve blood flow and delivery of nutrients to tissues and particularly muscle, then that would improve in theory, create a greater capacity to take up.

glucose into the muscle and store it and that would be an improvement. It ultimately improve glycemia and insulin sensitivity. So that was kind of the rationale for doing that investigation. So we did seven days of currents, supplementation versus a placebo, and this was in overweight and obese individuals. So they were inactive. We actually tried to recruit sort of what we call office workers, so people who were just sat.

in front of a desk for eight hours a day for most of the time and then do very little when they leave as well. And what we showed that you could, or what we showed quite nicely was that the Curranz supplement improved whole body insulin sensitivity just after seven days. That was quite nice. One of the, and that was assessed in the lab, so we do something called an oral glucose tolerance test. And again, it's sort of a clinical

test, if you like a very basic clinical test, you provide 75 grams of sugar basically or glucose and then after two hours of you take serial blood samples and you look at the glucose curve that is generated and you're looking to see how quickly that glucose is cleared from the blood as a kind of marker of glucose tolerance and insulin sensitivity. So that's nice.

quite a controlled environment. But what we also wanted to do is look at that outside of the lab and say, well, how does that affect, you know, if you had a high carbohydrate meal in the day, hopefully that also shows that you get less of a glucose response or less of an increase in blood sugars and it's cleared a little bit more quickly as well in kind of real life. So in that study as well, we used continuous glucose monitoring systems.

certainly in response to, I think it was the breakfast and the lunch on that kind of experimental day, although it was at home for those guys. They improved those sort of post-prandial responses to those two meals. We didn't see an improvement at dinner, but I think the carbohydrate content of the dinner meal wasn't particularly high actually, as it turns out. So that was...

potentially one of the reasons, but it was nice to be able to see that it works and we could show it worked in the lab and it also worked when people went home and were just going about their daily business as well. So that was really positive. Yeah. And I think from a mechanistic perspective, we weren't, we're still not entirely sure on what is driving that. And that's what we're trying to kind of figure out, figure out now really.

What we did see was during the oral glucose tolerance test, because as well as measuring glucose, you also measure insulin. And so if you get less of an insulin response as well, that suggests that whilst you are feeding the same amount of glucose, 75 grams, there's less insulin required to actually deal with that. So that suggests tissues where you're trying to.

dispose of glucose into, and that's mainly skeletal muscle, then it's more sensitive to any increase in insulin, basically, and would drive that glucose into the muscle and out of the circulation. So that's, yeah, that's, I guess, what we're literally starting to kind of figure out now. And we're taking a kind of two-pronged attack, let's say, at that. So we're trying to look at the mechanisms that are driving that.

what we call like conditioned serum. So basically, blood that we've taken from some participants, volunteers, should I say, after they've ingested the current supplement. And so we're getting increases in the anthocyanins and the metabolites, and that's what we're exposing the cells to. So then we look at some of the sort of molecular outcomes that are potentially driving that improvement in glucose tolerance and insulin sensitivity.

But we're also starting a dose response study there as well. So trying to figure out what the optimal dose is. And yeah, again, doing that in overweight and sort of obese individuals. And we're actually trying to. And also looking postmenopausal females, so with people who are sort of a bit more metabolically challenged, let's say, compared to younger, younger sort of overweight or obese individuals, that you sometimes don't always get that.

metabolic disorder showing its face quite yet. Yeah. So that's where we're going with that work, yeah. That's awesome, Sam. So, and just a few questions. One, was the dosing, did you do the sort of CGM monitoring alongside the dosing? So for that seven day period, they were taking the Curranz supplement, or did they take the Curranz supplement prior to for seven days? Yeah, so they took it.

prior to, and then it was actually on the eighth day that we looked at the CGM information, the CGM outcomes. I think, yeah, looking forward, if we repeat that sort of work, it'd be interesting to see how it, yeah, look at it over that seven day period, or however long we supplement for, and I suppose that's one of the things that we ultimately need to figure out is, all these studies are seven days. Yeah, yeah. But, you know, what happens if you take it in the longer term? Yeah.

whether that's for a performance outcome or whether it's for a health outcome, that's certainly an area that needs further work. Yeah. And then I wonder as well, you talked about the metabolites being present in the bloodstream for about six hours. So I wonder whether, I mean, it doesn't sound like unless they took the supplement on the eighth day, I was just thinking about the dinner meal. And you explained very well why there wouldn't be such a response, but I wonder if it would make a difference if they were as a double dose or something. I'm not sure.

Yeah, well, so the metabolites themselves will probably be in the circulation for about 24, maybe up to 48 hours. Oh, cool, cool, cool. Yes. That's the work that guys at another university in the UK have done. That's typically what we see. So that's right. You were talking about exercise for the six hours because we go through them a bit more maybe. Yeah, that's right. Yeah. And that's just my opinion on it. There's no evidence to back it up.

everything turnover in the body is much faster when we exercise anyway, so we'd assume that that's the same for the metabolites. But yeah, so I think one of the things that we're trying to look at here is whether you get this acute effect occurring. And we tried to do it in the study that I described, but it was probably a bit messy in reality because we tried to mimic sort of a...

what we might think of more typical feeding in maybe, or a meal that overweight obese individuals doing, we took quite an experimental approach to that. So we had like 50 grams of fat and 75 grams of sugar, and it probably, the fat just completely interfered with the glucose and made it really messy. So we didn't really see anything there. But one of the things we're gonna try and do in this next study is go, well, is it just that, just one dose?

the current is that having an impact on the blood glucose responses or is it this build-up over seven days or even longer if we want to extend this out ultimately? Is it that accumulation of the metabolites and do they accumulate over time that is then driving the improvements in insulin sensitivity or in any of the other cardiometabolic outcomes that we might think it might have an effect on as well? Yeah, nice. Sam, before we leave,

and I know, and I'm mindful of your time, are there any mitochondrial benefits from, because mitochondria is huge right now in terms of this sort of health science space? Yeah, so something that I've probably started thinking about in the last few months, because we've been quite lucky at Liverpool, John Moores, and got some nice new equipment to measure mitochondrial functions. Oh, lovely. So immediately you think, well, what can we do with that? And so, yeah, how can we play with that? And yeah, I think there is some...

potential effects on mitochondrial function for currents as well. Again, I think with our cell model that we're developing at the moment, that's one of the things that we'll be able to look at. And maybe we just measure some simple markers of mitochondrial function in the first instance, something like a creatine, sorry, a citric synthase assay or something like that, or just changes in PGC-1-alpha as the sort of master regulator of mitochondrial biogenesis.

And then ultimately look to see whether we're seeing changes in a functional measure of mitochondrial function as well. And then if that's the case, well, let's take it into humans and take some muscle biopsies because that's our favourite thing to do. And then see if we see the same thing in vivo and that'd be brilliant if we did. And whether there's even things like an additive effect with exercise or...

maybe it's more for people who don't do so much exercise. Can we enhance the effect of that exercise by supplementing with currants alongside that? But these are all open questions for the next few years. That sounds awesome, Sam. There's a lot going on. Do you take currants yourself? Of course, yes. Yeah. Of course. Same, totally. Yeah. So Sam, now just very briefly, and this really will just be a bit of a wrap up because I'm going full circle.

Is there anything that, so obviously we know what you're excited about in that black current space. And whilst you are sort of part of a wider team in the carbohydrate fuel for the work required space, but is there anything exciting going on in that space that we should be aware of coming out the next couple of years or? Yeah, I think, yeah, so for me, the, I'm really interested in that carbohydrate.

fat metabolism side of things because it's immediate application to athletes that you work with and you're going brilliant, like can we, you know, what's going to work and what's not essentially. And I think we've moved a little bit away from this, we understand that you, you know, periodizing carbohydrate is the way to approach these things for a lot of people. And some of the work that James and Mark Keiris has led in the last few years, showing that it's not really

The starting level of glycogen that's important, it's the finishing level of glycogen. So if your session is longer, intense enough, and you go below this glycogen threshold of about 300 millimoles, then you should see enhanced, at least signalling responses to exercise and whether they transpire to become an effect performance down the line. If you do that for weeks and weeks and months, then probably we don't quite know that yet.

They're very difficult studies to do, of course, in that world. So I think for me, the application of the carbohydrate periodization really comes down to knowing what the carbohydrate cost and the glycogen cost of typical sessions are. So we've kind of done a little bit of work in that space. Again, Sam Impey led this work. This was actually pre-COVID.

And it was quite nice because, again, we tried to take some of the stuff that we were doing in the lab in these very controlled environments to say, well, actually, what's the carbohydrate cost and glycogen cost of these sessions when we do them in the real world? So we took a lot of biopsies to look at this. And we did a big study where we had males and females, and they did three different running sessions that were what we couldn't...

at least understood from our links at the English Institute of Sport, that they were sort of typical 10k run sessions that people might do into, you know, who were training for that distance. And so one was like a 10 mile run. Then there was an eight by eight hundred sort of VO2 max session on the track and then a three by ten sort of LT1 sort of session. Again, we did that on the track as well. So many, many evenings were spent at the local track watching people run and then

taking muscle biopsies and we took biopsies from like the quad, but we also took them from the calf as well because we know that the glycogen data is a little bit cleaner from running purely through the, you know, you get greater activation of the calf and the gastrocnemius in particular. And so we started to build a picture of how much carbohydrate was required for those sessions. And of course, if you know that, then that informs how much carbohydrate you then need to feed or.

much you can or what's the minimum you can kind of get away with if you like to employ some of those periodization strategies. So I think there's work still to be done in that area and starting to understand that. But I think the other thing to understand and again this is goes back to the application is understanding the effect of feeding carbohydrate during exercise and is that going to influence any glycogen sparing and again we've kind of done a little bit of work in that area

least at the level of the muscle and probably the sparing effect is at the level of the liver. I think Mark, Kieris and James are just starting some work on that actually at this point in time where they're going to start looking at the effect of carbohydrate and feeding on and look at how that might spare liver glycogen using MRI scanning essentially and to measure liver glycogen levels. So that'd be quite neat but I think that has

application for how we fuel sessions because, and this was one of the issues when you first start doing this low carbohydrate work, it's impacting the quality of the session that you're doing. So yes, you're exercising with low levels of muscle glycogen, but you can't ride for as long, or you can't reach the same intensity, which we know is also important to drive the performance benefits that we want to generate from the type of training.

And so if you feed carbohydrate during those sessions, what effect is that having on muscle glycogen concentrations or liver glycogen concentrations and ultimately the adaptive response as well? So I think there's, yeah, kind of work to kind of do in that area. And then probably one of the things that I'm most keen on is, people joke because it's using microscopes. So I do a lot of microscopy work. Yeah.

proper science, isn't it? When you're at school, looking down the microscope is science. It is. And so, I've ended up doing that, which is great, but you end up spending a lot of time in dark rooms, which isn't so great. But we've started doing some work using electron microscopy and some of the... Yeah, ultimately, we're interested in looking at the compartmentalized glycogen use. So, the different... In muscle, you have different pools of glycogen. And

They probably play different roles in fatigue and self-singling and things like this. And so it might be that, yes, on a kind of whole muscle level, we don't spare glycogen with carbohydrate feeding, but it might be that a specific pool of glycogen is being spared. And that's something that we're just working on now. So.

some of the samples that we've collected from previous studies, we're starting to look at that using the electron microscopy. So that'd be quite neat as well if we were able to answer that question. Yeah, for sure. It's so interesting that blood, that muscle glycogen sparing story. So whenever we're having carbohydrate, when we're training, it's hitting the bloodstream and we're utilizing it as fuel, but that's not slowing down the rate with which we are converting the glycogen into to be also used as fuel.

Yeah, essentially it's a weird one. I think it's like a funnel. I always think of it like a funnel. I mean, it's interesting that you're kind of, yeah, you're putting your muscle glycogen and also your blood glucose into that and they're both going down at the same rate. Because when I compare that to the lipid story, where we know that you've kind of got your muscle lipid and your plasma fatty acids, well, actually, if you pour more plasma fatty acids in, it stops and starts to suppress the fat.

that you're using in the muscle. So I think that's, it's quite almost paradoxical in some ways that that's what we're seeing. But yeah, starting to understand why that is, I think is probably, yeah, certainly where that work's going to go. And hopefully I can stay involved with a little bit of that as well. Yeah. And Sam, finally, you've got, you're taking a lot of muscle biopsies to sort of figure out these, the answers to these questions.

for the athletes that are in this study, how then might just your general endurance athletes take that information to be applicable to them who probably not gonna get their legs sort of like, I don't know, chopped in or whatever. Yeah, they don't particularly like doing it, to be honest, as you can imagine. But no, so I think it's more about understanding for me

someone a certain level of carbohydrate, then we can make a good estimate on what level their muscle glycogen is going to be at. And then if we know, you know, if we say that, you know, someone goes for a 10 mile run and they, you know, on average from our study, you might say, well, they're burning X amount of carbs. And you see that as a reduction of, you know, X amount in terms of glycogen, is that going below the threshold is probably an important question, but how much in general?

you can start to think about how much glycogen you need to start that. And we know that you can, from the studies that Mark Harris has done more recently, you can really understand how much glycogen is used based on your kind of starting amount of glycogen as well and exercise. So it's just all going to build a picture in that respect. So when we start to, as nutritionists, we start to say, well, for this session, we'd need to

fed this much carbohydrate in the 24 hours before because we know that you're going to use X amount and that's going to lead to a certain level and we also need to be looking ahead of course what's the next session people are going to be doing but I think that'll come in time as we start to really understand the sort of carbohydrate cost of those sessions and build that into how we support athletes with that. Nice.

Sam, thank you. You have been a wealth of information in all of my areas that I'm interested in. Can you just let the listener know how they can find out more about what's going on in your lab and the research that you're involved in? And of course, I will pop the link in the show notes as well. Yeah, so I'm not a big social media fiend. I've got to be honest, so Instagram and Twitter, I'm not big on that, but a lot of the stuff is coming from there.

PhD students but typically all the information is on the Liverpool John Moores University webpage that is my webpage so a little bit more information about what's going on on there really is the main way to find out some. That's awesome. Sam, thanks so much for your time this evening, really appreciate it. Thanks, thanks very much.

Alrighty, so, I mean, what a geek out on loads of things that I'm super interested in and I really hope that you enjoyed that too. And do not forget your opportunity to get Curranz for 25% off your first purchase with their original 30 capsules using my name, Mikki. And also, I would remind you that the legend that is Simon Cochran, Ultraman, he mentioned them on this podcast.

and credited them for part of his recovery process. So, you know, they are used by legends like Simon and me as well. All right, team. So questions, comments, queries, all the things you can catch me over on Instagram and Twitter @mikkiwilliden. You can catch me on Facebook @mikkiwillidenNutrition or head to my website, MikkiWilliden.com and purchase one of my plans or book a one on one consult with me.

Alright guys, you have a great week. Talk soon. Bye.