00:00
Hey everyone, Mikki here, you're listening to Mikkipedia and this week on the podcast I speak to Dr James Dorlish. He's a researcher whose work challenges many of the traditional assumptions around energy expenditure, weight loss and personalised nutrition. Dr Dawling's research spans multiple large-scale studies including the e-mechanic trial and the e-calorie trial, both of which we discuss in depth on the show.

00:30
So these studies reveal that traditional metabolic equations often overestimate energy burn, particularly in certain populations. So we chat about that, we chat about differences in how men and women and people of different ethnicities respond to exercise in terms of energy expenditure. And this raises really important questions about the accuracy of fitness trackers and calorie calculations, which I know many people rely on to...

00:58
accurately assess the energy expenditure for the purposes of weight loss, weight maintenance, or weight gain. Beyond metabolism as well, we tackle the hype around DNA-based nutrition plans and the reality of individual variation in weight loss outcomes. So James is really involved in some pretty fascinating research. He is a lecturer in human nutrition at the University of Glasgow.

01:24
research focus on the impact of nutrition and physical activity interventions on obesity, metabolic health, and aging biomarkers. His work explores appetite regulation, eating behaviors, and how these factors change in response to lifestyle interventions. Dr. Dawling completed his undergraduate degree in sport and exercise science at the University of Bath before earning his PhD from Loughborough University, where he investigated the effects

01:53
and obesity-related genetic factors on appetite and appetite-related hormones. And we chat a little bit about that too. He then continued his research as a post-doctoral fellow at the Pennington Biomedical Research Center, studying the influence of calorie restriction and exercise on weight regulation, aging and metabolic adaptations. Dr. Dawling's work has been featured in leading scientific publications and podcasts, where he discusses the intersection of metabolism,

02:21
exercise and behaviour change. His research challenges conventional wisdom around weight loss and aims to refine personalized strategies for improving health outcomes. So if you've got any interest at all in areas related to metabolism, energy balance, weight loss, using caloric reduction or an increase in expenditure, I think you're going to really enjoy this episode. Before we crack on into the interview though, I would like to remind you that

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is to hit the subscribe button on your favourite podcast listening platform. That increases the visibility of Micopedia and amongst literally thousands of other podcasts out there. So more people get the opportunity to hear from the experts that I have on the show, including Dr James Darling. Alright team, enjoy the conversation.

03:14
James, thank you so much for coming to speak to me this evening, your evening, Thursday. You're looking at the future. Friday is looking bright, a bit warmer here probably than where you are. Really keen to chat to you about your research on metabolism. It's such a fascinating conversation. I don't know how much you're in the social sort of media world, but this is a topic that everyone is talking about.

03:43
Yeah, absolutely. Metabolism is absolutely critical in so many functions and so many diseases right now, namely obesity, but also other diseases like type 2 diabetes and cardiovascular disease. In the West, those issues are prevalent and I'm sure in other industrialized parts of the South as well. So yeah, metabolism for that reason is a critical area of study.

04:12
Yeah, and do you see, like if you are on social media and you see people talking about metabolism, are there things you see people saying you're like, if only they didn't say that or gosh, they've got that wrong. Like, does that something that comes up often for you as an expert in the field? Yeah, occasionally. I have to confess, I don't follow social media too much, mainly because there's just so much poor quality stuff out there and a lot of...

04:41
different camps and I don't think people will always consult the evidence to inform their opinions. Nevertheless, if we talk about diet and weight loss, which is the primary area that I'm interested in, it does frustrate me sometimes that people get in these camps of this macronutrient is going to help this to induce weight loss versus this macronutrient.

05:11
on the whole probably play a relatively small role in impacting weight loss. There are certain macronutrients which might make you a little bit fuller than others. But on the whole, it's about stimulating a calorie deficit. And sure, there may be a particular diet which is high or low in one macronutrient that might help you and might have helped you lose weight. But that doesn't mean that that's going to translate and help somebody else lose weight. So when I see

05:41
Just when I hear that in conversation with anybody really, it kind of frustrates me a little. Yeah, and I guess this is why podcasts are great and being able to chat to people like you is a really good thing because actually it's really common for me to talk to academics and researchers in this space who aren't out on social media, sort of putting those wrongs right, if you like, because of those sort of frustrations, but this is an opportunity for people to actually hear

06:10
from experts in the space. Now, I'm quite keen to kick us off James with you just giving us a little background on what got you interested in metabolism actually in the first place. Yeah, it's quite a long story, I guess. I mean, growing up, I was always super interested in kind of sport, exercise and fitness. I loved football or I don't know if you call it soccer down in New Zealand, but I kind of...

06:39
as soon as I knew that I wasn't good enough to be a professional, I kind of knew that I wanted to get involved in work in that kind of area, sport and exercise. So I did sport and exercise science in my undergraduate degree. While studying there, I kind of realized that working in sport was actually quite dog-eat-dog world and it doesn't pay you particularly well and the jobs are super, super precarious.

07:09
about the real fondness for kind of the influence of exercise and health, and how exercise impacted metabolism, and how it impacted certain appetite regulatory hormones. So that was kind of the link into my PhD. And really, I've been kind of sticking with that and studying that ever since my PhD really.

07:37
Has anything really surprised you along the way, James, with your studies in metabolism? If you think about, and obviously we're gonna come on to three of your particular studies, which I'm super interested to explore more with, but if you just think sort of big picture, was there something about the area that you sort of came into the field thinking that did not turn out to be true, or your research has sort of shown that wasn't the case? Like,

08:06
any of these sort of misconceptions that you had? Yeah, there's a few. I think one thing that coming in, like when during my education, you kind of, I was very much focused on kind of the impact of exercise on health and we'd get people, relatively healthy people from the university, during this is during my PhD, into the lab and we'd get them in these very nicely tight controlled environments and

08:35
would do these really methodical, mechanistic studies where we would measure their energy expenditure, measure their food intake, and then assess all these outcomes related to metabolism, appetite, and all that kind of stuff. However, well, and that kind of, you kind of develop an evidence base based off that and you say this caused this and that would translate into the real

09:04
study in Louisiana in the deep south of the United States. Now this is what we called a pragmatic trial, meaning that we were working with people who lived in rural areas of Louisiana, which is very much a very unequal society. And there's a lot of disparities when it comes to obesity, whereby people from poor backgrounds tend to have been at higher risk for developing obesity.

09:34
And we did this weight loss intervention in those that this group of people and we actually found that people who were what we call food insecure, so that is people who didn't have access to already readily access to a good quality nutrition actually performed less well in their weight loss relative to a group who were food secure and did have access to adequate food sources.

10:04
And then it's kind of, it jumped out to me then that there's so much more to understanding or influencing somebody's weight loss journey than just a particular intervention. There's so much social economic factors that can play a role and can impact how successful weight loss and your subsequent metabolic effects on top of that as well.

10:35
So it wasn't so much a surprising finding. There were people working on the trial who said that this would happen. But for me coming down to the chemist's lab background, it really was a striking and profound finding. So just to clarify, the people, so despite the fact that they may have been on similar calories, those in the less secure environments struggled more, or they just didn't have access to types of foods that allowed them

11:04
to be successful in their weight loss approach? Yes. So the food insecure people lost less weight than the food secure people. We don't actually really know why that was. We were all prescribed similar interventions and we tried to adjust certain confounding factors in the models. But they were losing less weight and they were performing.

11:33
less well in other outcomes as well, certain cardiac cardiometabolic endpoints. So yeah, we kind of need to understand why that is and kind of need to remedy that. But just seeing that was very much, yeah, it was a real eye opener for me. Yeah, super interesting. Like I talk a lot to people about diet quality, because you do have, I mean, like, obviously, at the end of the day, when someone needs to

12:02
or wants to lose weight, they need to elicit that calorie deficit, as you say. However, it is more than just protein, carbs, and fats. It's like, what are the nutrients do we need to support the body in terms of energy metabolism? I don't know. Or the ability to feel more satisfied. Or I'm thinking about fiber versus highly processed refined foods versus...

12:31
the same number of carbohydrate coming from foods, for example, that also contain fiber and vitamins and minerals. I often think about that food quality thing as well. But to your point, you're so right. There are so many factors that we just don't know, don't understand, and almost probably don't even know to measure either. This is why a lot of them aren't accounted for in the research laboratory.

12:59
It's an incredibly complex condition. The actual condition of obesity is highly, highly variable. And the causes are polygenic. There are multiple causes. There are physiological reasons why there's genetic differences between people that will predispose you to obesity because of slightly more hunger or maybe slightly lower energy expenditure. There's

13:26
psychological factors in there as well that play a big role, whether your quality of life is good and your particular mood. And as I alluded to, there's just luck when it comes to socioeconomic factors as well. So yeah, to say that there's one cause of obesity or that there's one cause why somebody is losing more weight versus another person.

13:53
is just a little bit reductionist and it's a whole host of factors. Yeah. Now, before we get on to your research trials, have you yourself ever thought about your own like food? Have you ever had to think about your food in the context of body weight? I know lots of people don't have to really worry about it, but... Yeah. Yeah. I mean, naturally being in the field, I mean, this varies among my colleagues, but I find, given that I study this thing,

14:22
24 seven and I encounter this the research every day that I do naturally kind of think about the kind of habits that I'm engaging with. I mean, as I said, I've come from an exercise physiology backgrounds and exercise has always just been a habit I've kind of taken up and it's just a natural thing that I do and try to fit in frequently.

14:48
When it comes to food, yeah, you pick up little pockets of information from the work that you do and think, oh, that might actually be a good idea just to kind of try and sustain my body weight in a healthy range. So, yeah, I try and watch my portion size, try and stock up on healthy foods, not buying too much bad types of foods, which may cause weight gain over a long period of time. But I'm not too rigid. There are occasions I do let my hair down.

15:18
and enjoy myself because that's, you could easily get quite excited on these things and it can actually be detrimental actually in terms of your long-term weight trajectory. So yeah, just a reasonable degree of restraint. Yeah, no, that sounds perfect and I wholly understand sort of where you're coming from. Like for people, like often in our field,

15:47
studied nutrition and my master's was in obesity. It's very easy to sort of be pulled in one direction and then it's sort of like you evolve your thinking as you sort of grow your knowledge base and things like that to be slightly more balanced and a bit middle ground. So if I turn to some of these research papers, James, which I've found super interesting from a geeky perspective, I mean, the first thing that stands out obviously is

16:15
It almost seems like in order to publish a study, you have to have a really good name for it. If I'm looking at your studies. Like there are some pretty clever people out there. Right. Yeah, yeah, yeah. They do a lot more creative and clever than myself. I tend to stay away from that stuff because I tend to be more focused on the scientific detail. But I mean, there are people employed at some of these places who's one of their key jobs is to come up with these names. So...

16:44
credit to those guys for if you think the names are good. Yeah, they do a fantastic job. One of your first trials that I want to chat about is the e-mechanic trial. And it's a study on energy expenditure. Well, I mean, that's quite a big picture way to describe it, but looking at metabolic equations and how they estimate energy expenditure. So can you sort of chat through maybe just the premise of the study and then also, yeah, just maybe the

17:14
premise of the study first? Yeah, yeah. So the eMechanics study was exercise randomized control trial. For this study, we recruited about 200 participants and we randomized them to one of three groups. There was a control group who engaged in no exercise and then there were two exercise groups which differed based on the amount of exercise that they did. So there was one exercise group

17:43
who did physical activity around about the guidelines here, while it was in the US, so around about 150 minutes per week. And there was another group who completed exercise of around about 200 minutes per week. And that was a six month intervention. The reason why we conducted this study was because it's been known for a while

18:13
induces substandard weight loss. On itself, on its own, exercise does not tend for most people at the guidelines anyway to stimulate clinically significant weight loss of 5%. That's because generally the calorie deficits that you can attain due to exercise on its own are quite low when you compare it to diet. But there is a...

18:42
Prior to the study, there was a gathering evidence to suggest that there may be some form of compensation going on by individuals who exercise. It seems that there was some kind of compensatory behaviors that people post exercise were engaging with and that could be the reason why, or another reason why, weight loss is not quite as good as expected during training.

19:10
So yeah, so what we did was we basically got them on this training study and we assessed a whole load of mechanisms to understand what could be the reason why they are not losing as much weight as expected. So we measured food intake, other forms of energy expenditure and physical activity as well. Yeah, okay. So the compensatory behaviours could have been that they were eating a little bit more because they were training.

19:38
or they were less active outside of exercise because they exercised. But then also, were you looking at some sort of compensation in just physiologically, like are we turning the dimmer switch down on immune function or something like that? Were you able to sort of explore those elements in this trial? Yeah, I mean, we hope of a size that it was primarily due to energy intake changes.

20:08
And our evidence seems to support that, that the primary compensatory mechanism, the reason why weight loss is pretty poor in response to exercise on its own is energy intake. But we also did some really nice measures in a group of participants in the study. We got them in what's called a metabolic chamber.

20:32
and we measured their activity and we measured their energy expenditure in a really controlled environment to see whether maybe they were not, maybe their resting metabolic rate actually went down or was altered in some way. We didn't actually show too much. There was a slight reduction in the energy expenditure through physical activity. So this is the activity that was outside of the exercise itself, but not too much.

21:01
We also took estimations of physical activity for all of the participants outside the lab. Again, for those who lost very little or showed an increase in body weight, because there were some people who actually gained weight, there was a slight reduction in physical activity as well. But on the whole, in general, it was the increase in energy intake, which was the primary driver

21:30
or weight loss. Okay. So were they hungrier? Yes, for some people there was an increase in hunger. It wasn't quite as clear cut as what we were expecting. And the reason why I don't think we saw quite a clear cut increase in hunger in some participants is because I think there's an element of kind of conscious

22:00
rewarding that's going on by the participants in response to exercise. I never forget there was a time I was involved in a study during my PhD and it was a HIIT training study. So a very short amount of exercise and I was chatting to one of the participants and at the end of the one of these sessions I said, what are you up to for the rest of the day? And he said, well, since I've gone training, I've started just going off to my local fast food restaurant and picking up a big

22:30
just as kind of, just to kind of cool down. And I was thinking, oh, did you feel like, that you feel, does your body feel like you need that? He says, no, I just kind of been doing that just to kind of give myself a pat on the back at the end of training. So I think that was kind of a bit of a light bulb moment and go, okay, actually there's some form of conscious compensatory behavior going on that can occur irrespective of the physiological hunger that you're actually experiencing.

22:57
So to answer your question, yes, there are some people who kind of show high levels of hunger, but there are some people who just kind of consciously reward themselves for engaging in the activity and just give themselves a pat on the back. Yeah, that sort of the more uncomfortable you are during that session, probably the higher that sort of reward factor might for some people come in. And I often talk to people about having about, you know,

23:24
I don't think necessarily, and this is actually a bit off topic, but I don't necessarily think it's a bad thing to have the extremes that reward, particularly at the start if someone's just beginning to get into exercise. But I try to say to people, can we make it align with your goal actually overall? Is there something else you can do that's not like a big old thick shake? Which actually...

23:48
I've just come in from a run, James, and that right now sounds really good, because it sounds really cold, which is quite nice. So your study also found actually, from on reading it, that the traditional metabolic equations overestimate energy expenditure, especially in certain populations. I think this is interesting because almost all of us have either sport watches, or we've got maybe...

24:18
work bands or we're looking at what the exercise cycle tells us in terms of calories burned. And then of course, you've got my fitness pal saying you need to eat back your calories. So what did your study sort of tell us about energy expenditure with regards to that? Yeah, this was a really nice sort of supplemental analysis. One of postdoc at Louisiana State University.

24:46
University, Rachel Matthews and supervisor Neil Johanson, they made a really interesting observation that the equations that are typically administered by the American College of Sports Medicine to estimate energy expenditure during exercise, they were derived from a set of studies that only included a handful of people.

25:16
males who were white. Young? Relatively young. I can't recall the age up the top of my head, but yes, quite young and probably quite fit, although I don't have that data at hand. But what we started talking about was that there's a huge degree of variability in just natural energy expenditure between groups of people. Men and women differ.

25:45
males and females differ quite significantly in their energy expenditure. And there's also a lot of variability in racial background as well. So differences between white and blacks. And we had quite a heterogeneous sample. So there was quite a good mix of people. So what Rachel did was she did an analysis where she tried to see whether the American

26:13
and equations to measure energy expenditure during exercise were aligned with actual energy expenditure which we had during the trial. She showed two really nice findings. The first was that the equations generally overestimate the amount of calories that you burn during exercise. That overestimation tends to get worse the more training you do.

26:42
the longer the training goes on for. And two, there was quite a degree of variability based off race. And actually, black women actually in the trial did, there was a large degree of overestimation. So the equations did not work so well for that group of people during the trial. Which then really calls into question how...

27:11
accurate they're going to be for a whole bunch of different populations, I guess. And what was the degree or do you like, do you have an idea of the degree of overestimation sort of at its worst? Like, what are we talking? Yeah. So I think Rachel did an analysis, which basically showed that for kind of a 30 minute session, if you were to get kind of a white person on a kind of a treadmill at a particular speed.

27:40
and first as a black person and for about 30 minutes or so, you're talking about a 40 kilocalorie difference between the overestimations of the equation. So, I mean, if you're kind of somebody who is black or is a black woman in particular, and you're using these equations to kind of estimate the amount of energy that you're expending.

28:08
That equates, if you're following the guidelines of about an overestimation of about 200 kilocalories per week. That's not monumental, but it is over a long period of time that could play a role. And then if you add on to that the fact that there could be these other compensatory mechanisms as well, you really probably...

28:34
from that group and you're engaging these added behaviors and you're using these equations, you can very easily see why weight loss might not be as good as you expect. Yeah, and I guess this is one of the reasons why sort of best practice, I guess, people out there in the field would never say, eat back the calories that you lose that are reported during that exercise session because it's such an inaccurate measure. And I imagine that

29:03
fitness level has got to play a role as well. The body, I've been running for 30 years, the body, my body's very efficient at what it does now compared to someone who might do a similar session and have a similar effort, despite us being maybe of a similar age or a similar sort of body composition, it could still vary quite a bit, right? Oh, yeah, certainly. I mean, as I said, one of the findings did suggest that these equations

29:33
and tend to overestimate the amount of calories that you burn to a great extent the longer the training went on. So it was almost as if this efficiency that you spoke about was developing very quickly in these participants, because they were sedentary going into the trial, but the longer the trial went on, there was a greater discrepancy between the amount of calories that they were burning versus the amount of calories that these equations were predicting.

30:01
So that there could be multiple reasons for that. This was a treadmill training study. So these people were walking on a treadmill throughout the study. There could be this kind of biomechanical efficiency that's being developed during the trial. There could be some metabolic processes going on. Don't particularly know why, but yeah, I think you're right. Fitness is certainly another factor that could play a role.

30:28
how habitually active you are could also be impactful. Yeah, how aligned is your work with the likes of Herman Ponce's lab, James? Yeah, so Herman Ponce's work suggests that there's a kind of an upper limit of kind of energy expenditure during extreme exercise workloads. I wouldn't say our findings are really aligned at all.

30:56
We didn't really see any clear decline in energy expenditure because remember we actually did measure the energy expenditure. We weren't using the ACSA everquakes to actually assess the differences but we didn't see too much of a decline in energy expenditure if I'm honest but Herman Ponza's work, I mean he uses a completely different set of people for his studies.

31:26
who live in rural areas, who are physically active all day and are kind of up on their feet. We were dealing with predominantly a sedentary population living in America. If you've ever been to America, most people are sedentary. They kind of go to their office job and that's it. So yeah, I don't really think our findings in any way kind of align with his.

31:53
but they are two different studies at the same time. Yeah, yeah, no, that's fine. I was interested because of research in the field of metabolism looks at, I guess, multiple different populations and answers multiple different questions. And even if it sounds similar, like clearly that's quite different. I'm interested, just this is related to what we're discussing, but you know the MEPS.

32:22
So you know, if you're looking at estimating calorie requirements, and then you add on a physical activity factor and you use the metabolic equivalence, like walking is 1.1 and gardening is 1.2 and lying down is 0.9. Do you know those numbers? And is that something? Yeah. So how accurate are these numbers? Because I know many people go on to try to...

32:50
figure out for themselves what their energy requirements are, and they use these numbers to determine how active they need to be. Do you have any opinions on that? Yeah, I mean, for me, would I wholly trust that these metabolic equivalents that you speak about are accurate? I'm highly skeptical. We've talked about...

33:18
several reasons why or several factors that could influence how accurate they are. And just in the mechanics study there, there are probably a whole host of genetic factors, things like race and sex that do influence the accuracy of those equations. Nevertheless, I do quite like the idea of having some kind of resource for the general population to access.

33:46
to kind of get just a rough gauge of how much activity or how much an activity is burning at a particular point in time. Even if you're not getting accurate calorie estimates, it's still good to know that you're gonna burn more calories if you go out for a 10K kilometer an hour run versus doing the gardening. So, they're still a useful resource, even if they don't always.

34:16
give you accurate estimates of calorie expenditure. Okay, and that makes sense, I guess, because you look at sort of trends and the direction of certain things, rather than trying to pin a particular number and knowing that this spin class is 600 calories. Well, because it's maybe 50 minutes long, you're gonna burn more calories than maybe that 30 minute class that you did, but that doesn't really matter. Yeah, yeah. And another critical thing, like we haven't...

34:46
I haven't really spoken about this thus far but exercise on its own is not a fantastic way to lose weight by itself but it is a fantastic way to stimulate other metabolic health benefits. So even if you don't lose huge amounts of weight, it's likely that if you're sedentary, you will still gain significant health benefits. If you'll become a lot fitter, which is related to mortality.

35:15
improve certain kind of metabolic related endpoints, things like blood pressure, your blood glucose regulation, and that's all very important. So yeah, these tools and these resources that give an estimation of how much weight you could lose or talk about the potential of weight loss are great. But if we can get people to exit even do just a little bit of exercise, it's a really will have huge impacts for a person if they are sedentary start with.

35:46
James, can we talk about the calorie study? Of course, yeah. Yeah, yeah. Talk to me about, give us the premise in the background of that study and what you did and what you found. Yeah, so calorie was a two-year calorie restriction intervention. So this like a mechanic was a randomized control trial. We had a control group who for two years were told to just consume their habitual energy intake. And then we had a calorie restriction group.

36:16
who we put on a calorie restriction diet for two years. What was really intriguing about this study was that the participants were not obese going into this intervention. And the reason why we were not to recruit individuals with obesity is because we were looking to see the influence that calorie restriction would have on

36:43
a relatively healthy group of people and how it would impact markers of aging. So there's evidence to suggest that if you adopt calorie restriction relatively young in life, so I'm talking like early adulthood, that you can delay or even prevent age-related diseases and you can extend your lifespan. That's evidence from animals. And so we were

37:13
would investigate whether chiropractic was indeed effective at stimulating these age-related benefits in a relatively young, healthy population. What markers did you look at for that? Because obviously the ultimate end marker is not possible to measure. Yeah, you're absolutely right there. So we took a whole bunch of measures in this study. So we looked at

37:40
a bunch of inflammatory markers. So that includes C-reactive protein, TNF-alpha. We also looked at your traditional cardiometabolic measures. So as I've spoken about already, systolic blood pressure, blood lipids, blood glucose, blood insulin. But we also took measures related to body composition and psychological health as well. And also how their eating habits outside of the lab changed.

38:08
That was an area I was particularly interested in. And we found that calorie restriction was effective. The people did lose weight and they saw significant improvements in inflammatory markers and improvements in certain cardiometabolic disease risk markers as well. And what's really, what I find really interesting is that going into this trial,

38:36
these people were not obese and their cardiometabolic measures were within healthy ranges going into the study. So they had healthy blood pressure, they had healthy blood glucose regulation, but this calorie restriction intervention was still very potent at improving those measures further. And so what we think, what we kind of posit based off this is that if you kind of adopt a kind of a healthy calorie restriction like diet.

39:06
and sustain your weight at pretty healthy levels during kind of young adulthood, you can delay or even potentially prevent all those kinds of diseases that come and hit you later on in life. So things like cardiovascular disease, things like type 2 diabetes and cancer, and ultimately we think extend your lifespan. So that was, it's kind of in a nutshell what

39:35
what the study was about and what was found. Yeah, and what level of restriction are you talking about? Because as I understand it, if I'm looking at the rodent research, they appear to put the mice on like 30% less calories or something that sounds quite miserable and they live a bit longer, but I mean, would you really want to do that? Yeah, yeah. So in the trial itself, we aimed

40:03
to stimulate 25% reduction in energy intake. We achieved about 20% at six months. So we were pretty close at getting 25% early on in the trial but naturally as we often find during these types of trials adherence wavers a little bit and you get this kind of.

40:31
weight regain phase where people are coming, the waist coming back up and they're not sticking to their calorie targets quite so much. When we did the overall maths at the end of the trial, we found that we think that on average there was about 11% calorie restriction over the two years. So, about 10% calorie restriction. And that was still, even though we didn't

41:01
a very effective intervention at triggering all these beneficial health benefits. Did their weight change? Yeah. Yeah, the weight loss was seen compared to the control group. It went, I think it was about 10%, about six months and I think it may have, it wasn't on 10%, I think it may have been about 8%.

41:27
the difference between the control group at the end of the two year intervention. Yeah. And what does that tell us, James, I guess, about the normative ranges with which we're told to sort of shoot for in terms of body weight, in terms of blood lipids, in terms of glucose metabolism? Are we just a little bit shooting for mediocre in everyday life and in fact, we need to just sort of dial it in a little bit further? Like, do you have any thoughts on that?

41:57
Yeah, that's a good question. I, you know, these kinds of the thresholds that we have in society, at least here in the West, I mean, they're there for a reason they do. They are related to disease. So, for instance, if your blood pressure is above 120 over 80 millimeters of mercury, you know, you're probably going to be at increased risk of

42:25
cardiovascular disease relative to someone who's lower than that. What I think it shows is that even if you meet certain thresholds or certain normative values that you can still do a little bit better. Even if you do a little bit better, that's still going to improve your risk further. If your blood pressure is 119 over 80.

42:54
That's fantastic and you're probably going to do pretty well relative to a lot of other people in the population. If you reduce that to 111 over 80, you're gonna gain even greater benefits and it's likely that your risk for cardiovascular disease will be even better later on in life. So I think those are the things that I kind of...

43:20
think about when I talk about the kind of colour results and how it could affect society at all. Yeah, so I mean, you used machine learning models in your study and it showed that's like a really good level of accuracy in predicting weight loss success. So what are some of the most actionable predictors that an everyday person can focus on to maximise success based on the results of your study, do you reckon James?

43:49
Yeah, so this was a really interesting and novel piece of work led by a group in Germany who got involved and thought that they would try to apply this machine learning. Just as a backdrop to that this kind of analysis, researchers have been investigating if there are certain things going into an intervention that can predict whether somebody's going to lose weight or not during a particular weight loss trial.

44:20
Is there something about the environment? Is there something about your genetics? Is there something about your characteristics that can give us a firm indication whether you're going to lose weight or not? Because there's quite a lot of variability. And generally, these studies have been pretty unreliable and they haven't been able to identify factors reliably. This particular study tried to kind of...

44:46
take an objective approach and just put everything together and see if there were variables that were related to weight loss. As you said, there was pretty successful identifying a whole bunch of factors, some of which were surprising and some of which were not so surprising. In terms of answering your question about, are there things that somebody could do?

45:16
One of the things that we've shown quite reliably is that the degree of weight loss that you lose early on in an intervention is actually a good indicator of whether you actually lose weight loss in the long run. We've shown this in exercise studies and we've shown this in dietary-based studies that those who generally lose the most weight early on tend to lose the most weight.

45:45
years later. I mean, these are the kind of big long term studies have shown this. We recently published work which showed that during a weight loss intervention, you can predict after about two weeks who is going to lose clinically significant weight loss of about 5%. So, we found with pretty good reliability that those who lost 2.7% of their body weight after two weeks were able to...

46:11
had a good chance of actually attaining 5% weight loss after two years during a weight loss intervention. That is still, I think, if I'm asked to provide recommendations for people to track how well they're doing or try and predict how well they're going to do, that's still probably the best way. These analyses, these machine learning tools,

46:38
They're pretty good, but these are still very much in their infancy. And we've produced a nice little study, which I think scratches the surface and identifies some variables that may be predictive of success. But I don't think I would, given how kind of small, relatively small the analysis was and how much more these machine learning tools have got to develop, if we're quite at the stage where we can say, before an intervention,

47:06
okay, you've got this particular characteristic, you're going to do well versus this other person who hasn't got this characteristic, they're not going to do well. Yeah, and I guess, you know, it's interesting listening to you talk about weight loss and listening to the percentages that you're throwing out there in terms of what's successful, what's successful long-term, et cetera. And many people might be listening to this going, 5%, you know, they might be sitting there thinking, I've got to lose 20 kilos, which is...

47:35
a whole lot more than the numbers that James is talking about, but you're looking at this from a health perspective and there is some clear evidence to show that even losing 5% of your body weight, if you carry excess body weight, has really quite profound impacts on health, right? Absolutely. Yeah. So these thresholds, these targets, this 5% number, it comes off the

48:05
studies which suggests that in individuals who are overweight and obese, if you get to 5%, you're going to see significant health benefits. So you will get improvements in kind of blood glucose control and your blood lipids will improve, blood pressure will go down. Things like quality of life as well, certain psychological factors also improve at 5%. This is a whole group of studies that have kind of shown that. So that's kind of like the...

48:34
the clinical threshold that is applied in general when somebody is on a weight loss intervention. Now that's not to say that even greater weight loss shouldn't be targeted. And indeed, there's quite often during these studies, particularly before my time when I was involved in science, they would try to get people to reach for 10% because generally for a lot of these kind of health outcomes that are related to obesity.

49:04
the more weight loss you achieve, the greater benefits you're going to get. So if you lose 5% weight loss, that's great. You're probably gonna get an improvement in your blood lipids, but if you lose 10%, those blood lipids are gonna improve even more. Your quality of life is going to improve even more. So yeah, we have this 5% clinical threshold, clinically significant weight loss that suggests that if you meet this target, you will see some benefits, but...

49:33
for most people with overweight and obesity, it's generally suggested that you should maybe target more. Yeah. And James, you mentioned that you were particularly interested in the psychological piece of the calorie study and those psychological markers, because, and I sort of throw it through in there quite flippantly, the 30% miserable mice models that, you know, also showed benefits in terms of longevity. Like any...

50:02
anything that stood out for you in terms of the psychological element of that calorie restriction, which in the end, doesn't sound like a hardship to be honest, like, you know, 11% of calories or whatever across two years. Is that what you also found? Yeah. So by and large, when you look at a whole bunch of psycho behavioral measurements,

50:32
to kind of eating disorder symptoms. The calorie restriction intervention didn't really affect any of those negatively. When we compared those to the control group, things like mood and sleep, this is self-reported, but nevertheless, it did actually improve in the calorie restriction group. So yeah, there may be this kind of this notion that if you adopt...

51:00
a really restrictive diet, that you're going to stimulate all these negative consequences and you're just going to feel miserable eating your celery and all that kind of stuff. It's not like that and our results don't really suggest that. In fact, for most people, they may actually just actually feel quite a lot better. They've lost a bit of weight, they're seeing these metabolic improvements. It might actually be beneficial.

51:30
100%. I mean, your study does a great job at providing proof, if you like, that long-term weight loss at a level which is sustainable, so it's not too aggressive, can actually improve the quality of life. And people just feel more in control and not feel so deprived. And they're getting a lot of the benefits from it.

51:58
feels like it's a real win across the board actually. Yeah, yeah, it is. And I mean, you said at the start of this section of the conversation that it does sound miserable. And if you translate that into kind of how much life expectancy or how many extra years or months of life you actually attain, it may not be worth it. But as I said, what we suspect, and we don't have the data for this in humans yet.

52:28
But what we suspect is that what the real potential of calorie restriction is that will increase what we call health span. So, these are the years of your life that you are free of disease. Okay? So, these years you won't have your cardiovascular disease, your type 2 diabetes and cancer, all these things that generally occur later on in life for most people. We think those...

52:56
those diseases and your risk for those diseases are dramatically reduced if you adopt a calorie restriction diet or you just adopt, keep yourself within a healthy weight throughout your adult life. And I think that when you frame it like that and you think, yeah, actually, no, I don't want to spend the last fifth of my life, last 20 years of my life in and out of hospital with type 2 diabetes, going to the doctor's every so often.

53:25
That's where I think the appeal of colour restriction and the attractiveness of colour restriction is where it really lies. Yeah, I totally agree. And I was thinking about this this morning, actually, because I was listening to a podcast talking about, I mean, these types of topics. And I remember hearing in a conference last year that in the UK, that a woman who lives to the sort of the expected lifespan

53:55
of being in poor health. So that's the gap between healthspend and lifespan. And for a man, I think it's like 16 years or something, which is crazy long. Yeah, it is. It's a long time and I mean, it negatively affects your quality of life. But from a societal perspective, it puts a huge strain on health services as well. There's going to be issues. I mean, this is a whole other podcast, but there's going to be huge issues with global aging in the coming years.

54:25
Here in the UK, if you walk into a hospital, I mean, we have a public health system here in the UK. It's filled with people who are in the later stages of life and they all have, well not all of them, but most, a lot of what's prevalent for a lot of these people are these obesity related diseases. So I have said them countless times here, things like cardiovascular disease, cancers, type 2 diabetes.

54:53
all things that we think we can maybe delay or prevent and or at least reduce the severity of fruit diet early on in life. If we could make a dent and improve that, that would be huge for our healthcare systems throughout the globe.

55:23
of brackets, I think we're slightly different in terms of our ages, but I feel like a lot of people sort of kick that can down the road because they're not seeing in real time what impact their diet and their exercise habits are actually having on their health. It's just something that they're going to have to sort of deal with later on, but it's very easy to ignore if it's not in the here and now. Yep, yeah, absolutely. And there's a lot of work in animals to suggest that actually the earlier

55:53
The earlier in adulthood, so once you get to about the age of 30, the earlier you adopt calorie restriction, the more benefits that you are likely to attain later on in life. So if you are kind of in your mid 30s and you adopt a healthy diet that's relatively low in calories, you're more likely to completely prevent any kind of age-related disease and would be more likely to enhance your lifespan later on in life.

56:23
versus say someone who's 50, kind of developed obesity, and then your dog's carrier restriction at that stage, they're likely to gain less benefit. They will gain some benefits still, but it's the amount that they can achieve in terms of their health span and lifespan is likely to be less. Yeah, nice one. James, I'm mindful of the time, but I do just wanna ask you a couple of last questions based on the points study.

56:51
which I also looked at and which is obviously clearly speaking to the same topic on diet and sort of the best diet for someone if you like. And one of the reasons why I do want to just have a quick chat about it if possible is because there are so many different recommendations out there for diet and increasingly we're looking at this real personalized nutrition based on our genes.

57:20
I've been through a course to look at genetics and the impact that certain gene polymorphisms or someone's sort of genetic makeup and what it tells us about their propensity to inflammation or maybe what the cholesterol does or their propensity for weight gain. Can you talk us, just give us a brief outline on what the points study looked at and then how this relates to this sort of personalized

57:50
diets that we can get based on our genetics. Yeah. So, I mean, as you alluded to that, given the kind of the variability that you see in response to weight loss, it's always been postulated that genetics does play a role in kind of how somebody loses weight. So in this particular study, we got a group of people who were overweight and obese, and we utilized a set of genetic polymorphisms.

58:19
tend to be specific. We categorize them as what we call carbohydrate responders or fat responders. Based off literature that's been acquired to date, the carbohydrate responders should theoretically respond well and by respond I mean lose more weight on a high carbohydrate diet. Whereas those who are fat responders should lose more weight on a high fat diet.

58:48
So what we did is we got those groups of people and then we randomized those people onto either a high fat diet or a high carbohydrate diet to see whether the categorization as a fat responder or a carb responder interacted with the diet to improve weight loss. Yeah, and so the...

59:10
The markers that you were looking at to determine whether someone was a carbohydrate responder or a fat responder, are these markers that anyone can just go and get? They are, yes. So you can get just standardized kind of, these kind of ancestry-based tests. You can take a little blood sample. The kind of the standard.

59:35
outcomes or the outputs of these types of tests don't provide you the information, but I think if you do a little bit of digging, you can try and determine precisely what these polymorphisms are. Yeah. And when you're talking about high fat versus high carb, what percentage of the diet were the participants targeting to be in those particular groups? Yeah. So if a participant was on...

01:00:04
randomized to a high carbohydrate diet, they would consume a diet which was about 65% in carbohydrates and 20% in fat, 15% in protein. For the high fat diet, protein was still 15%, but fat was 40% and carbohydrate was 45%.

01:00:33
65 more in that ketogenic range? So in terms of I'm talking about the diet that was provided here. Yeah, yeah, yeah. Exactly. So the 65% carbohydrate in the high carbohydrate diet, as opposed to 45% in the high fat diet, 20% in the high carbohydrate diet, 40% in the high fat diet. Nice. And they're getting tongue-tied. No, you are. You are. So give us the rundowns. What did you find?

01:01:02
Yeah, so we basically once we categorize these people as carb or fat responder, we then sort of split them up and then randomize half those people into a high carbohydrate diet, half those people onto a high fat diet. And we actually found that amongst all of the groups, weight loss was exactly the same. So all the groups, we put them on these diets that will

01:01:27
on a calorie deficit of about 750 kilocalories a day, but they differed on this macronutrient composition. They all adhered to the diet and they all lost clinically significant weight of about 5% over three months. But the actual weight loss that they achieved was the same regardless of whether they were a carb responder or a fat responder and regardless of what diet they were put on. What does that tell us then about

01:01:57
genetics that play into whether or not we're going to tolerate carbs or fat more. So what it suggests to me is that currently with the knowledge that we have, we probably can't categorize somebody as kind of a carb responder or a fat responder and then put people on diets based off relatively simple information that we have to date.

01:02:26
said to you, we used 10 polymorphisms to determine whether somebody was a carbohydrate responder or a fat responder. I suspect that there are hundreds, if not thousands of other polymorphisms which could play a role influencing whether somebody is more likely to stick to one particular diet versus another. And I suspect there probably will be differences in how well they.

01:02:53
or genes that influence how well people respond to different macronutrients too. We found that in this study, our results suggest that genetics don't really play too much of an impact in how well people respond to particular diets. I still think that there could be a role for genetics. I think one day I can fit them.

01:03:21
a scenario in the future where people are giving a blood sample and taking a bunch of other characteristics on their lifestyle, on their socioeconomic status, and there will be diets tailored to those factors, including genetics. But right now, with the current information that we've got so far, we're not quite there to administer these personalized diets. It's all about

01:03:51
just trying out different methods and just trying to find a diet which suits you and which you can kind of see results fairly quickly. That's probably a diet. And you can stick to. And you can stick to. That's probably the best. It's a dull answer. It's one we kind of... People are kind of a bit disappointed when I tell them this information. When I tell them that I study genetics, I say, oh, yeah.

01:04:19
I thought you had something a bit more sexy to say, but unfortunately, we just don't have that information at our hands yet. I do think there will be a time where we will be able to make sophisticated diet plans that are very personalized and well evidenced and may play a role at stimulating improved body weight regulation for people over time. But we're not there yet. I feel like it is quite funny, isn't it? Because

01:04:48
You know, there's a ton of research in the field of what it takes to elicit meaningful weight loss and also weight loss that people are able to maintain. Like, you know, this is a question that so many people are trying to answer via various methods, but at the end of the day, we're still sort of the number one message I'm getting from you, James, and a lot of other people I talk to is...

01:05:17
what can an individual adhere to over an extended period of time that also elicits that calorie deficit required for fat loss. And whilst, which I think probably is quite a, it might almost be a relief for a lot of people who think, damn it, now I'm going to have to go and get my genetics measured and it's quite an expensive exercise and then pay all of this money for all of these other supplements because it is quite complex and albeit things are very...

01:05:45
complex when it comes to obesity, but potentially the solution at an individual level really is just more simple than it's, I don't know, than what we can be led to believe sometimes. Yeah, you just said that really nicely. Sometimes you might have to experiment a little to kind of identify what is the best strategy for you, not just the best diet, but the best

01:06:16
way that the diet works, the way that it fits into your lifestyle. I'm a big advocate of just tracking body weight. Some people, it makes them a little bit uncomfortable. And I do understand that. But the proof is in the pudding, you can very quickly see whether a diet is working for you. You should start to see weight come off relatively quickly. But you're absolutely right. The key is

01:06:45
strategy, a diet and a routine that will trigger this calorie deficit. And with that calorie deficit, you will see weight loss. That will over time, you can't keep losing weight, the body responds with very effective mechanisms to fight back. You may have to adopt different strategies at different stages of a weight loss journey, once you kind of hit a plateau, which is very common for a lot of people. But

01:07:15
Yeah, if you can adapt and you can kind of adopt these strategies, it is possible. It's not easy. And a lot of people will struggle to kind of sustain weight loss over time. And that's perfectly normal. But it is achievable. It is doable. And I feel like sometimes we are sold this lie that it should be effortless. But in fact, there is always effort in anything that requires, you know.

01:07:43
that is worth doing, you're always going to have to put some effort in and instead just try to appreciate the fact that you're able to actually do the thing. I don't know, I always think like that too. It's worth the effort, so don't complain about it, just get on with it. Yeah, right. I mean, and give it a try. I mean, we're seeing a lot now as well with .. There's a lot of new strategies that come out. I mean, we haven't spoken about it, but a lot of pharmacological agents is a bit out of my wheelhouse.

01:08:13
These are hugely effective tools and very useful tools for a lot of people who've gone and tried a lot of diets and haven't had much success and they've made a real positive impact as well. But I still like to see data suggesting that we can trigger a lot of health benefits and we can trigger long-term weight loss with diet and with lifestyle.

01:08:41
I still think that should be at the forefront of a lot of strategies to help people sustain a healthy body weight. For sure. And I guess maybe in 10 years time we can expect that you will explode on social media because you have hit the magic bullet when it comes to the exact genetic makeup required for this particular diet. But until such times, James...

01:09:10
where is the best place that people can find out more information about the research that you're doing in your research lab? And of course, I'll put links to the studies we're talking about in our show notes. Yeah. So I'm on Twitter or Hexas is called now. The tag is at James D PhD. I'm also on

01:09:37
search for my website on the University of Glasgow webpage or any in any search engine just put my name and University of Glasgow and that should come up with details of my publications and everything. Yeah, no, it's a great resource actually that's how I got your papers. James, thank you so much for your time this evening. I really appreciate it and really look forward to.

01:10:04
what's next for you and your lab in the next couple of years. My pleasure. Thank you.

01:10:24
Okay, hopefully you really enjoyed that. I really enjoyed talking to James, such a great guy. And you know, I'm really interested to see where this research is leading over the next five to 10 years, particularly as we begin to rely more on AI and wearables and things like that. Next week on the podcast, I chat to Dr. Alex Bartle, all about sleep. You are going to love that conversation. Until then though, you can catch me over on

01:10:53
threads, Twitter and Instagram @mikkiwilliden, Facebook @mikkiwillidenNutrition, or head to my website, miikkiwilliden.com, and book a one-on-one call with me. All right guys, you have the best week. See you later.