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00:03
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.

00:24
Hey everyone, Mikki here, you're listening to Mikkipedia, and this week on the podcast, I speak to Dr. Amy Goss, Assistant Professor and Researcher at University of Alabama in Birmingham, about nutritional intervention for fatty liver disease. Specifically, how a low carbohydrate diet can help with this condition. So we begin by talking about non-alcoholic fatty liver disease.

00:53
how it develops and the problem with it in a pediatric population. We talk about how Dr. Goss' research shows that a low carbohydrate intervention effectively reduces fatty liver disease in both children and adults and we discuss how her diet interventions also improved diet quality and how this rolled out and what their findings actually were. We also discuss some other projects that Dr. Goss

01:21
is involved in including an LCHF approach with regards to improving overall health outcomes for metabolic health in adults and some surprising findings on how fattening french fries might be compared to say almonds, a health food. You guys know I love a french fry. A fat chip. Okay, let's be fair, a fat chip.

01:46
This is a super insightful conversation with Dr. Goss. She is leading the way with regards to this type of research. And it was such a great conversation. I really think you're going to love it. So Dr. Goss is an assistant professor of nutrition sciences at University of Alabama, Birmingham. She's also a registered dietitian and an early career investigator with expertise in conducting

02:13
randomized clinical trials to examine the effects of diet quality and macronutrient composition on risk factors of chronic metabolic diseases such as obesity, non-alcoholic fatty liver disease, and type 2 diabetes. The goal of her research is to identify effective, sustainable, and non-invasive dietary means of preventing and reversing disease with metabolic origins.

02:42
techniques for the assessment of fat distribution and organ lipid contact in both adult and pediatric populations and has recently conducted studies using the family-based controlled feeding experimental design aimed at proving outcomes in children with NAFLD. And you'll hear us talk about this in the interview about just what goes into running these types of trials. And my goodness, they are not cheap. But it's super.

03:12
encouraging to see the results of these research and how they are using those pilot studies to inform larger trials and that there's the support for that in their research funding which is really cool. I'll pop a link to where you can find Amy at the University of Alabama and also on Instagram so you can find more of her research.

03:37
Before we crack on into the interview though, just a reminder 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 the literally thousands of other podcasts that there are, so more people get the opportunity to learn from guests that I have on the show like Dr Amy Goss. Alright guys, enjoy this conversation that we have about non-alcoholic fatty liver disease.

04:07
Amy, thanks so much for taking the time to speak to me today. So I really enjoyed your presentation at Low Carb Denver. And then I sort of got looking into your other research papers and thought it would be an awesome opportunity to discuss metabolic health, non-alcoholic or metabolic associated fatty liver disease, I think is what it might be referred to now. And just some of your other sort of interesting papers. But...

04:37
Can we start with your background? So can you sort of tell me a little bit about how you got into, well, I guess medicine at first, but then of course, more specializing in this area? Certainly, yeah. So my background when I, you know, my undergraduate degree was in dietetics and I went to the University of Georgia and then following my bachelor's of science in dietetics, I moved to Birmingham, Alabama, where I went to the University of Alabama at Birmingham to do...

05:06
a dietetic internship. And I was really doing rotations as a part of that to become a registered dietitian is when I fell in love with the research side of nutrition, just feeling like we're counseling these patients on certain diets and just realizing how many questions I think I still had about nutrition and what we didn't know. And at that time, I was just learning about...

05:35
the rates of all these different chronic metabolic diseases that were skyrocketing, you know, that were then and still are now. And it really drove me to the research side of nutrition. So I decided to stick around. I did my master's and PhD there, just focusing during that time on looking at diet macronutrient composition and the glycemic load of diets. And while that affected

06:04
metabolism and physiology, but more specifically looking at sort of body fat distribution through imaging techniques and how we can image the body and different organs and measure lipid and where it's stored and how it was really that type of fat deposition. You know, sort of I published some papers during my PhD that looked at sort of the protective effects of certain types of adipose tissue deposition. So...

06:29
subcutaneous fat being more protective when it came to metabolic disease, not really being a causative driving factor. And then how other types of fat deposition in the visceral cavity and in organs was more so linked to risk of diabetes and risk of other chronic diseases that were sort of being driven by insulin resistance and poor metabolic outcomes. So that's sort of how I ended up getting into

06:59
this space in particular. So yeah, I've got a few. I was thinking as you were talking, I've got a few questions. When did you start your masters, Amy? It was directly after my internship year. So it's kind of a combined program where you have a couple of options. You can either do coursework and a non-thesis to get your masters in nutrition or

07:24
thesis option and because I really wanted to go the PhD route, I decided to do a thesis for my master's, which was looking at hormones and body fat distribution and post-menopausal. Interesting. Yeah, interesting. In what year was that? That was back in, oh gosh, I think I graduated my master's in 2009. Yeah, cool. Yeah. And what was the space like in terms of nutrient distribution of diet and what we learned made people gain weight versus

07:53
what may have been out there in social media. Like how, like what was the landscape like back then? Yeah, so I'll say this, you know, under in my dietetics undergraduate program, and then even into my master's, what you know, until before I started doing research during my PhD, I was completely unaware of like, research going on looking at carbohydrate restrictive diets, I think.

08:20
I was myself, I was familiar with low glycemic load because I'd been practicing it for a long time as someone who has type 1 diabetes. I was diagnosed when I was 2 years old. And so really like, you know, nutrition being a really large part of my life and the management of type 1 diabetes is what, you know, got me into the field to begin with. My family followed a pretty strict like what at the time was the diabetes diet, which was low fat.

08:50
You know, not really an emphasis on carbohydrates, even though, you know, granted every meal I ate, I had to count carbohydrates. So, you know, I think it was, I think I was like a senior in high school or going into my freshman year, I read sugar busters and it was sort of like...

09:10
focusing on low glycemic, which was like kind of like a light bulb moment for me, like, oh yeah, like that makes sense. Learning how much easier it made it for me to manage my own glucose levels and, um, and that sort of thing. So then fast forward to, you know, years later when I was doing my PhD and ended up with a mentor that had a funded NIH study to look at the effects of a low versus high glycemic low diet on fat distribution.

09:39
beta cell function in adults that were at risk for type 2 diabetes. Oh, interesting. Yeah, so it all kind of came full circle for me when I was, you know, started in the PhD program at UAB. Yeah, and did that sort of knowledge change your own practices around your diet? I mean, you mentioned obviously the glycemic load, but later on, like, how has your own personal diet sort of changed with regards to carbohydrate restriction and things like that? Yeah, I mean, I...

10:07
Being a scientist, I like to experiment. But I'll always sort of fall back on sort of this low glycemic approach. Like for some days, you know, it's always some form of carbohydrate restriction, not necessarily very low. Because I really feel like from the research that I've done, I've seen very low carbohydrate diets work for certain people with certain metabolic phenotypes, right? Yeah.

10:37
And then for others, not necessarily. So I think it's like the way, you know, this is sort of speaks to precision nutrition and the way in which we can sort of figure out who's going to benefit most from which type of diet pattern. So for me, I'm like, I'm convinced that I'm, you know, I'm in a happy place when I'm doing just like a low glycemic load type diet. Some days, obviously, I'm like probably eating less carbs than others.

11:06
Um, you know, so I don't really like that sort of my general, you know, rule of thumb and what I follow. So. Yeah. And I love that. And it's like, you know, I spoke to Andrew Kootenach on the podcast, maybe two years ago now about his, um, type one diabetes and sort of discovering the low carb and, you know, even though his diet practices himself puts him in that low carb camp, he was also much like you, you know, you've got to work with, you know, individuals have to find out their.

11:35
what's a sweet spot for them, you know, and to keep their metabolic health and their energy and you know, much less stress and just a whole ton of factors must go into it. And you can't just go, oh, low carb for everyone or don't worry about, you know, that kind of thing. Yeah, that's something I, you know, I've been asked that before, like, and I try being like a scientist, I try not to like.

12:00
Sometimes I'm just like, do I share how I eat? Because I don't want people to think like just because I eat this way doesn't mean it's right for you. Yeah, yeah, yeah. So I think there are like general principles around like what, how you prevent disease and what a diet looks like to do that. But like then also what I've learned like specific disease states may need to approach diet differently if the goal is to like reverse disease and that sort of thing based on sort of like your underlying metabolic phenotype and genotype. So yeah.

12:29
Yeah. And you know, it's so interesting with that, because I do have a couple of questions about subcutaneous fat, and I will get back to them, but with what you say about specific disease states, because you know, the latest stats out of the US, and I don't know what, I can't recall where this comes from, although I even was just looking at it a couple weeks ago, like 93% of adults, apparently, or something like quite dramatic, have some level of metabolic dysfunction. Like, is that?

12:59
And you're looking specifically at disease states, and it sort of seems like we're talking to the majority of the population. Is that how you see it? Yeah, I mean, I hadn't heard that high. It was, you know, did you say 93%? Yeah, I think it was like 92 or 93. Like the last, it was 88, and then it had been revised to 93, and equally, like they're both pretty high. Yeah, they're both really high. Yeah.

13:27
Yeah, it's definitely something we see, you know, really often, like you've said, I've focused on both pediatrics and then also adult populations. And right now, I am funded to look in kids and it's just, you know, what we're seeing in kids right now is rather alarming, right? So, so, you know, as high as 40% of children, maybe higher than that, because it goes way under diagnosed have fatty liver. That's kids with obesity that also develop fatty liver, but then

13:58
I've heard a number higher than 20% of all adolescents and kids have pre-diabetes. So it's really just a shocking number. And what's kind of even scary about that is what we're seeing from lots of data that these diseases progress, it's a rapid progression in kids, right? Even more rapid than what we're seeing in adult populations. So it's something that I think...

14:26
I've been encouraged to see the level of funding that are in the United States in particular, like the NIH is willing to sort of fund these studies so we can look at these different diseases in kids and look at diet and different ways that we can address it through different types of interventions at the family level is what I'm really interested in. But yeah. Yeah. No, that's awesome. So I did my master's looking at childhood obesity back in 99.

14:56
And part of it was it was the, I think, what was it? It was doing some sort of scoping exercise to figure out, you know, how to intervene at an environmental level. So we were sort of in the environmental space, which like, obviously very difficult, but regardless, like part of the process was asking parents about their children. And so we had had the anthropometric measurements, so we knew how many children were overweight. But then if you were to ask the parents,

15:24
Like one third of the parents who had overweight children didn't recognize that their kid was overweight. And it was in fact, at that time, it was if you were what might have been considered of a healthy normal weight, if it was say the 1970s, like if you were that kid, you were actually deemed the skinny kid. Like the whole normalization, I think, of, or at that time, there was this normalization of this excess sort of...

15:52
body weight, I suppose. Do you have any thoughts or opinions on that side of things? Yeah. I have read papers around that topic. It's definitely not my area of expertise, the psychology that goes behind that normalization of what once was considered the standard versus we have a whole society that it looks different now.

16:21
So it's sort of this, it's what people are now used to, right? And it's, and that's not to say, you know, part of our research too is looking at sort of this healthy, metabolically healthy, overweight and obese category that it does exist. You know, and like I've kind of, I've hinted to earlier when we were speaking about the body fat distribution, like, you know, you can't necessarily attribute

16:49
metabolic disease to obesity per se or to the fat deposition because I believe those two things can coincide, but it's not necessarily certain types of body fat storage that are driving metabolic disease. I think it's sort of like the diet environment interacting with the genes and the phenotype to result in these chronic diseases that we're seeing.

17:18
And I am aware of it as well that the subcutaneous fat is a protective mechanism of the body to protect the bloodstream from having too much glucose or too many fatty acids and the complications there. So is there, is what you're saying that...

17:40
and we'll just speak about kids because that's what I want to move on to as well. But kids who might look a little bit bigger, it might be that they've got this protective mechanism in place that might be better for them in the long run with regards to where they can store fat. Yeah, I think subcutaneous fat is so fascinating because it's like having healthy subcutaneous fat that functions well. The purpose of it is to

18:08
store lipid and store excess. And that's sort of the appropriate physiological response to over consumption or over nutrition or a positive energy balance, right? It's when that subcutaneous fat stops functioning properly and storing lipid the way it's supposed to is when you start to see this deteriorating metabolic environment and metabolic health. So it's just a very interesting,

18:37
untangle what's happening with obesity versus how diet's directly affecting the metabolic health side of things. Yeah. And what causes a dysfunction in that subcutaneous fat? Is it the diet? Yeah. I think there's a lot to be learned here because we know that it can become fibrotic. It can...

19:03
can be infiltrated into the subcutaneous fat that does affect the function. And I think there's just like a lot of factors that can affect it. And I think it can be a direct effect of a poor diet quality. That sort of, you know, part of it, like I said, is genetics, right? Like there are, men tend to deposit less subcutaneous fat, more abdominal fat, also at higher risk of diabetes. And then...

19:30
across ethnicities, there's different types of body fat distribution patterns that we see. But it's pretty clear that like once that subcutaneous fat, if you can store a lot of subcutaneous fat, you may be protected from metabolic disease for quite a while. Yeah, yeah, yeah. Yeah, it's interesting. I know that they've done studies on sumo wrestlers. So clearly, like, I have this like amazing ability to store.

19:56
incredible amounts of subcutaneous fat yet they're very metabolically healthy whilst they are competing you know whilst they're still training and stuff like that super interesting. So Amy can we sort of shift gears a little bit and talk about metabolic associated fatty liver disease and the sort of problem in children and of course your research in you know what might help in this area so what is metabolic fatty liver disease?

20:26
Yeah, so I guess like in the literature right now there's a sort of a debate on what we should call it. Yes, what's interesting about the metabolic associated fatty liver disease and speaking with a lot of patients and patient advocates of folks who have had non-alcoholic fatty liver disease and even have liver transplants, they really they don't like it being called metabolic associated fatty liver disease, which is interesting. They prefer...

20:55
non-alcoholic fatty liver disease, just because from their, in certain demographics and their perspective of this condition, they want it to be clear that this is not alcoholic-associated fatty liver disease. So they actually like that terminology.

21:10
I've seen debate about what we should actually call it, but that's sort of beside the point. That's interesting. Yeah, it's interesting. I know in some areas of the field, they are trying to move towards that because it is associated with metabolic outcomes. Essentially it's liver fat deposition that's considered pathological, anything really above 5% lipid deposition.

21:36
that's not driven by alcohol, but it is technically driven by a number of factors, including dietary intake is the primary driver, but that when that's combined with sort of fatty acids that are being mobilized from adipose tissue and a suppression of fat oxidation in the liver causes this pathological deposition of liver fat. And it's really anything over 5% if you're measuring it by like an MRI or using that for spectroscopy.

22:04
So it's a very low threshold, right? It's like either you don't have it or if you get over 5%, you have it. And we've seen anywhere upwards of like 50%. So I mean, it's a wide range of liver fat deposition that we see clinically. But also once you start to deposit liver fat, it's thought that that's going to be the primary driver of hepatic insulin resistance. So the liver is sort of like, you know, a major site for...

22:32
glucose metabolism for insulin clearance in response to a meal, once insulin secreted in response to a meal. So there's a lot of things. The liver is like this metabolic driver, right? It's the primary site of fat oxidation. So once you're kind of shifting toward fat deposition and away from this fat burning in the liver, that's when we start to see these like metabolic abnormalities start to emerge. Yeah.

23:02
Obviously, we've sort of talked around and talked about some of the risk factors for dysfunctional fat tissue. Are they the same risk factors for fatty liver disease? Yeah. So with fatty liver, as I mentioned, like the diet drivers, essentially, it's like a high glycemic diet that where essentially like your insulin levels high, you're shutting

23:31
and engaging in hepatic denobulibogenesis, which is contributing to this suppression of fat oxidation, which is the manufacturing of lipid in the liver from other substrates. That lipid is more likely to be stored when you're suppressing the fat oxidation in the liver. Again, yeah, like so as you were mentioning about the subcutaneous fat, if there's sort of this background of insulin resistance in peripheral tissues like adipose tissue,

23:59
where insulin is no longer suppressing lipolysis like it should, and you're mobilizing lots of free fatty acids, the liver is being exposed to all of this, right? So then you just have kind of the perfect storm for liver fat deposition. And over time, you know, we used to think this was a condition that we only would see in adults later in life, but it's happening really quickly in these kids that really can be, you know, I think it's being driven by poor diet quality and really high intake of

24:28
of different types of foods with lots of added sugar, sugar sweetened beverages, fructose, you know, all these things are kind of like creating the perfect storm for this to happen. Yeah, does activity play a role at all, Amy? Like, so is it, or are active kids protected? Like, what's the relationship there? Yeah, that's a, I know there are plenty of studies showing that exercise is, can reduce liver fat.

24:56
And I think, you know, being physically active for some people can play a role in protecting against this. But then, you know, we have plenty of kids that are, you know, they play sports, you know, that sort of thing, still have fatty liver. So it's not just like a blanket. You know, these kids are all very sedentary because they aren't necessarily, you know, so I think.

25:22
you know, physical activity is really important for these kids to focus on as a part of like a healthier lifestyle. But also like the in my mind, the primary driver has got to be this addressing the diet. Yeah, yeah. And, and just do you have any opinions on I mean, it's such a not a loaded topic because there are so many places I mean, so many reasons why people eat what they eat and and what kids eat what they eat. But any thoughts around that? Like, what is what?

25:52
Is it just that the diet is just so different now than what it was 30 years ago? Is it school lunches? Is it the issue in school lunches? What do you think? Right. Yeah. So, you know, it's hard for me. I know with school lunches, there's some problems there with, you know, the guidelines that schools have to adhere to. But ultimately, that's part of the problem. It's...

26:20
There's also what kids are exposed to outside of school that's a problem. You know, I mean, it's a lot of it is drinking regular sodas all day. And there's only so much I think schools can do to address it. I think there are minor tweaks that could happen there, right? Like not focusing on avoiding fat in natural foods, right? Like milk and cheese and eggs and not sort of taking this approach that like low fat milk is OK if it has.

26:48
sugar in it, but whole fat milk is not okay. That seems a little backwards to me. Yeah, totally. And really just trying to emphasize getting less ultra-processed foods in the schools. Even though they might meet some other guideline like being low fat or being a certain calorie level, I think trying to move towards a system that could emphasize more whole foods that are low glycemic, higher in fat that are naturally occurring.

27:17
could be beneficial in the schools. Yeah, and just have more nutrients. That's the thing, right? All the other nutrients required. It's interesting, Amy, I was at Costco. It's just arrived here a year ago in New Zealand. Yeah. And at Costco, you can feed your kid for $3.50. You could have dinner for $3.50. You get a hot dog, you get two free refills of some sort of soda thing. There is Pepsi Max.

27:47
So there is a sugar-free option, but the majority of them are sugar beverage and fries and the rest of it. And there were just families sitting there eating at Costco and food is so expensive. And the type of food that is available to people is just, it's even more so, it feels even more so now than it has ever. Has it ever been? Oh yes, that is so true. Like it's a challenge, right? It's expensive. You know, I...

28:16
I can go into talking a little bit about our family-based intervention where we're trying to feed families their groceries for months and trying to follow a really nutrient-dense diet that's whole foods based is really expensive, especially if you're a family of four, five, six, seven. You're looking at...

28:39
thousands of dollars worth of groceries over a month, like lots and lots of money. It's much more cost effective to rely on, you know, the more processed foods that may not be as healthy. But, you know, so it's definitely a challenge to figure out how to address this. But, you know, it's something that's definitely worth trying to do this research to figure out how to make it more accessible to families to be able to eat this way.

29:07
So Amy, on that then, can we talk about your research and your family intervention? So what, so yeah, give us a little bit, obviously we've had a bit of the background, but talk us through what you did. Sure. So we did a pilot study several years ago that I think we published results in like 2021, 2020 or 2021.

29:29
where we did a pilot study, where we did a family-based intervention with two phases. There was like a short controlled feeding phase where we fed the family groceries for just two weeks and then a six week sort of free living phase. And then our purpose was to, it wasn't a weight loss diet. So we wanted to weight maintain the children, but just simply manipulate the macronutrient composition of the diet. So we tested two diets, one that was,

29:58
moderately carbohydrate restricted, so like 90 to 120 grams of carbohydrate per day, higher in fat versus a low fat diet that was higher in carbohydrate. We held the protein constant on both diets. So the diets were both designed to be like minimally processed, high quality, so we could really just kind of get at if there's some unique effect of like the carbohydrate fat content of these diets.

30:26
And what percentage, Amy, sorry, of calories would have been from carbohydrate in those two scenarios? Yeah. So the lower carb, so the percentage varied a little bit depending on the calorie level for the kids who really wanted to clamp it at like less than 120 grams a day. So it was probably around like 15% carbohydrate. It was under 25 for each kid. But yeah, so around like, so it was pretty low. Yeah.

30:55
And then, and obviously you're going to have the same variation with the high carb diet, but what, what like more up around the guidelines of 55 or 45 or? Yeah, I think it was 55% that we aimed for that for that diet. Yeah. So yeah, so it was, we would like, we measured their resting energy expenditure to try to get like a really robust sort of direct, it's not direct, but a close measure of energy expenditure.

31:22
So the families are randomized to one of these diets. We did MRI and like a fasting blood draw baseline and eight weeks. We did a DEXA scan to look at body composition of the kids. And then the kids were expected to attend one session per week with a dietician with one family member to sort of just check in, see how they were doing with the diet and adhering to whether or not they were adhering to it and that sort of thing. So.

31:50
After eight weeks, we found that our carbohydrate restricted diet did in fact induce about the kids on that diet lost about a third of their liver fat in just two months. Amazing. Which was great. I know we were so excited. But what's interesting about this too is that those kids actually sort of self-restricted energy. So even though we didn't want them to, they still calorically restricted. Yeah.

32:18
And how old were these kids, sorry, Amy? I think our youngest was eight years old. So it went all the way from eight years old to 17. So it was sort of that adolescent period, but younger. We're seeing it in pretty young kids, like six or seven. We didn't include those, but we had some that tried to enroll. So it's appearing in pretty young ages. Yeah, so.

32:46
So we're really excited about those results. They did, you know, this group, they lost weight, they lost the liver fat. They had, you know, improvements in other outcomes like their insulin resistance that we measured by HOMA, which is like sort of a rough estimate of hepatic insulin resistance, since it's calculated from fasting levels of insulin and glucose. So it's sort of considered like a reflection of hepatic insulin resistance. Improvements in their blood pressure.

33:16
lost abdominal fat mass. So we just across the board saw these like really great outcomes in just two months in these, in these kids. Um, which, you know, we were surprised like this, it's sort of an age group that's really tough to do an intervention with. Um, yes. Were the entire family following the same approach? Yes. That's what we asked them to do. So like the grocery delivery delivered enough for the entire family, um, to have meals together.

33:42
and do that. And it's sort of, you know, we didn't have the money to do it longer, but in which we do now in our in our larger intervention that's ongoing now. But at the time, this was like a pilot study. And we sort of thought of it as like, we'll deliver groceries for two weeks, sort of get them accustomed to like the types of foods they should be shopping for. We'll provide them all the menus for the entire eight weeks, the recipes.

34:04
the grocery list, but we can provide the food for at least the first two weeks. Oh, amazing. So post that two week grocery haul, they then went on to eat, to buy their own food, et cetera. Yep. We tried to design it to be like relatively budget friendly. They were given every detail like this is the food to buy, this is the menu, this is how much the child needs. And so

34:34
So we're excited that even though there was like a six week free living phase, we still saw significant results with the kids. That was amazing. And what were the families, obviously, after you guys, when they were doing their own food, like, did you get any feedback on how difficult it was to adhere or a cost issue or just even the meal plans? Like, how did what's some of the feedback around that?

35:00
Yeah, so I mean, our families were so great. You know, we obviously would have, we've had dropouts, right? If the kids are just too picky, you know, there are just reasons why they would drop out. But a lot of the kids that were in the study, they just, they would tell us this was so much easier to follow than we thought it was going to be.

35:23
They enjoyed the food. The parents would come in being like, we feel amazing. We've lost weight. Even though we weren't really collecting data on the other family members, there was sort of this trickle-out effect or whatever. They were all sort of having these positive benefits from what they were doing. So it was all very encouraging. So in general, we get great feedback from the kids.

35:51
They don't think it's that tough and it's a lot of food. You know, once you sort of strip away a lot of these like calorically dense foods that are, you know, highly processed, it ends up being like a lot of food to eat, like a weight maintaining diet. So I think, yes, they feel satiated. You know, so I, you know, we just get a lot of positive feedback for the most part. Yeah, amazing. And then you use the results of your pilot study to inform your, now.

36:19
Larger study. Yes. Yeah. So we once we got this pilot data published, we went in for an R01 grant, which is, you know, it's a grant from the NIH that it's over five years and it's roughly like 500,000 a year. So about 3,300 over $3 million grant. So we went in back in 2020, and it was successfully funded. And so we started recruitment.

36:47
about a year ago on that. So essentially with the larger trial, it's instead of, you know, this first one was just eight weeks. This one's going to be a six month trial. We have the funding to feed the families for the first three months of the study. So we have dietitians, they design the diets, they meet with the families, they they schedule like grocery delivery through Instacart or ships every.

37:14
I don't know if you'll have that. I know what you're talking about. We don't, but I know what you're talking about. Yeah. So they get their weekly grocery delivery and sort of the same sort of framework that we use with the pilot. But it's just like sort of we're trying to recruit 80 families over the five years. We're doing, you know, we're still doing the MRI at three different time points. So we do baseline after that feeding phase and then.

37:39
another three months where we're calling it like a free living phase that they're expected to continue on the diet. So we're just kind of seeing if they can maintain it after we're not providing food. And will they still have dietitian meetings in that free living phase as well? Yes, what they do less frequent. So I think at that point, it's twice a month they check in to kind of see how it's going. And we try to collect food records to see what they're eating during that phase and that

38:09
So, and I think, you know, it's interesting this new study too, we're doing some more sort of more rigorous metabolic testing with the kids. So at baseline and then it's at three months after this controlled phase, we're doing a euglycemic hyperinsulinic clamp with tracers. So these labeled glucose tracers, so we essentially can figure out specifically if the liver...

38:37
insulin sensitivity is improving with depletion of the liver fat. So I think that's going to be some really exciting data to get. And then also one of our aims is to sort of look at the plasma metabolomics, sort of like untargeted metabolomics where we can see if there are any sort of like signatures around different metabolic pathways that may be changing in response to these different diets that's linked to liver fat and depletion of liver fat. So...

39:05
I think we're going to end up some really nice sort of data from this. And what would that tell you, those plasma metabolites? Yeah. So the metabolites, our hope is that we can identify some biomarkers that either are really closely associated with degree of steatosis and then also that track with change in liver fat. That could be like a non-invasive and inexpensive way of like tracking liver fat long-term.

39:33
and over time with these kids. And then the metabolites are the end products of these metabolic pathways. So we can get at what these diets are manipulating to cause the digestion of liver fat. So yeah, so it's untargeted. So we have certain things we are looking at, but it's a fishing expedition to see.

39:58
or what's associated with what and that sort of thing. So, yeah, amazing. You know, it's, I'm really interested to know how, you know, how would parents know if their kid had non-alcoholic fatty liver disease? You know, like, so what kind of signs and symptoms would these families have then caused them to go to the doctor to then have the diagnosis? Right, and that's the thing is it's just like, it's a pretty silent condition. Like most people can go.

40:25
their whole lives without knowing they've had it. And I've heard stories about people that have, maybe over time they've gotten their blood work done, their liver enzymes have been elevated, but they were never sent for like an ultrasound or anything like that. And then they end up with end-stage liver disease and needing a transplant because it was sort of something that was kicked down the road for so long.

40:50
And part of the reason that happens is because there isn't a drug to directly reverse it, right? It usually does present individuals with overweight or obesity. So a lot of times these kids, they will go in for like a primary care type visit with a pediatrician. And the over time, if there's persistently elevated liver enzymes, sometimes they'll be sent to do an ultrasound.

41:16
But not every time. So we work closely with UAB. Well, so Children's Hospital of Alabama, which is the largest children's hospital in the state, is like right across the street from our department at UAB. So we get to collaborate with them pretty closely. The physician's over there and it's, you know, unless you're in a big city like that where you're seeing specialists and that sort of thing, sometimes it just goes undiagnosed for a long time.

41:46
And Amy, are triglycerides and insulin and glucose, like are these blood markers at all helpful that you've seen? Like is there, yeah. Sometimes not always. And what's so interesting, I think that's why we like desperately need some sort of biomarker that's reliable, right? Like he's even that liver enzymes can be very like unpredictable and not necessarily reflect.

42:14
the degree of liver fat and how serious it can be. So, I think the fasting insulin could be a great marker in some people, maybe not everyone, because it can reflect that insulin resistance that's associated with the fatty liver. And then also, yeah, the triglycerides are frequently elevated with non-alcoholic liver disease. So yeah, those are some more. I know there's some like...

42:43
surrogate when there are studies of published different surrogate ways of measuring liver fat with these different blood markers. I think there's still a lot of work to be done, something that we can hang our hat on that it can be a great tool for clinicians. Yeah, for sure. I'm thinking about the load of carbohydrate in the restricted group. It's actually like if you're coming at it with a low carb

43:12
lens, it's actually not that low carb compared to say, a ketogenic type diet. Like I, um, what kind of carbohydrate intake would these kids or would kids in general normally be eating? Do we, do we have that data in New Zealand? We don't know what we eat. Like last nutrition survey they did was 2008, 2009. So, you know, very out of date. Yeah, I would say, I mean, gosh, I, I can't, I'm trying to think of something that's in publishing kids to sort of give an idea of what

43:41
the general population is eating. I would say, I mean, I'm assuming it's really high carb because that's what when we collect baseline information on our kids that enter the study, it's, you know, it's high carb, it's really high. So I would be surprised if it was anywhere near like moderate to low, you know, that kids are typically eating. You know, that's, yeah.

44:09
And I guess, you know, if you can get the success with this moderate carb intake, then there's no real requirement maybe to lower it further to see what a ketogenic diet would be. Cause then that would just, you'd have, I imagine issues with adherence and a whole host of other things, I guess. Did that ever, when you were designing the study, you were ever thinking, ah, I wonder what this would do? Yeah, yeah, that was a major consideration. Cause I've done studies with ketogenic diets

44:39
And we've prescribed it clinically in our department to people. So I've seen firsthand the major metabolic benefits that can come from that in certain populations. So in designing the kids study, we just thought it would be like a tough sell. And that it's this push and pull, like you said, with adherence. Right? Like how...

45:04
How drastically do we need them to change the diet to see the benefits that are gonna be clinically meaningful? We were able to pull that off with like, allowing the kids to have like 30 to 40 grams of carbohydrate with each meal, which is still, and it's granted they're low glycemic carbohydrate sources. Like, what are we talking lentils and- I mean, we're talking like- Bismarie or? I'm trying to think what kind of stuff we had like,

45:34
They would get some carbs from like, like really high fiber, like pitas or wraps. Everything just had to be high fiber and low glycemic, like some like sweet potato maybe, or we tried to keep like the white super starchy stuff off the diet, you know, so it wasn't rice or like white potatoes or pasta. So we just, but we had to focus more on like,

46:01
The non-starchy vegetables got plenty of those, probably got some carbs from like yogurts and things like that. Carbs from fruits that were pretty low glycemic and that sort of thing. Yeah, nice. And Amy, with metabolic associated fatty liver disease, are we just not aware of what an issue it is? You know, like I don't feel like it.

46:29
gets a lot of airtime out there where, you know, the focus is on, you know, obesity and type 2 diabetes and things like that. But this is a real concern or it feels like a real concern. Right, right. I know it's the numbers we see with fatty liver, you know, I feel like there's so much lower than what they really are. Like there's so many people walking around, they don't know they have it, you know, you wouldn't know unless you're going to get an MRI and you know, that sort of thing. So

46:58
I think the numbers are much higher than we think. I think it's a precursor for a lot of the diseases we see. The hepatic insulin resistance is sort of a driver for a lot of different metabolic diseases. And again, the liver is the primary place where fat oxidation occurs, right? So if we're talking about body weight, if your liver is not oxidizing fat, then you don't stand a chance of losing weight or like maintaining your body weight.

47:28
So I think liver health is like something that's sort of not talked about enough, like you said, you know, and how we like optimize diet and optimize lifestyle to sort of keep the liver, you know, metabolizing things the way it needs to. Yeah. And, and for, and I guess this is for both children and adults alike, like once they have reversed their fatty liver, are they now required?

47:56
to be low carb forever or for an adult, like if they reverse their fatty liver, are they never able to enjoy a glass of wine again? Like what is the implications of having it to begin with for your sort of long-term practices? Unfortunately, there's like no long-term data on this. So I think it's, you know, definitely questions I have about what that looks like, you know. My suspicion is that

48:23
this is a lifelong condition. If you've developed fatty liver, you have to the rest of your life be cautious, right? And you can't go back to possibly what the way you were, you know, your lifestyle prior to reversing it, because you might end up with it again, right? Because there's a highly genetic component to it. You know you've got sort of like the underlying physiology that puts you at risk for it.

48:51
I'm thinking if someone uses a very low carbohydrate diet or is very restricted, there's a chance that once they reverse it, they can sort of loosen the reins on that a little bit and maybe eat more carbohydrate, continuing to focus on low glycemic load sources. I think that's a great question. We need more evidence to suggest what the maintenance phase looks like once you reverse disease. And I think that's the case for a lot of metabolic diseases like type of diabetes.

49:21
once you reverse it, what does that look like to maintain that for the rest of your life? Yeah, that's like a critical question that needs to be answered. Yeah. Oh, interesting. So when does that particular study end? So you got the grant in 2020, was it? And then are we looking 2025, 2026? Yeah, we're looking probably 2026 is when we'll wrap up recruitment and try to get...

49:49
the first publications out from that data. So have a few years to go, but- Yeah, yeah, yeah. That's always the hard part is like wanting the data soon and then having to wait for the pub to come out. But yeah, so we're excited. We have some more studies wrapping up where we are looking at sort of the effects of very low carbohydrate diets compared to low fat diets and weight maintenance conditions and type two diabetes. So in the absence of weight loss.

50:18
We were looking at specifically pancreatic lipid to see if low carb would deplete pancreas lipid and cause the beta cell to spring back to life and restore first phase insulin secretion and beta cell function in patients with type 2 diabetes. Really trying to get at that EDL, that underlying beta cell function issue with type 2 diabetes. It's the driver of type 2.

50:48
Yeah. And what are you finding? Like, is it too early to ask you what you're sort of finding there? Yeah, we don't know yet. We don't have the data analyzed. We're wrapping up recruitment in the next couple of months. So we should have papers out soon and abstracts and like conference presentations with that data soon. So I think it's going to be really exciting stuff. Yeah, nice. And that's a very, so is that more in that ketogenic space that you're like 50 grams or below, 25 or below? Yeah, it was, I think it probably is.

51:18
was like less than 10% carbohydrate, so it was pretty low. And I think the participants were technically in ketosis. So yeah, it was similarly a three-month controlled feeding study in adults with type 2. So we'll have that data pretty soon, which I'm excited about.

51:38
That sounds awesome. Amy, it's funny, I've got two other papers here. I'm like, oh, I'd love to talk to Amy about these. But I'm very respectful. I want to be respectful of your time. I know a lot of actually with one of the papers, we have probably talked a lot around some of a similar information, but particularly with the LCHF as a strategy for central fat for middle-aged adults. That was a paper which I found sort of interesting. Can we just...

52:07
What is the utility there? Like what, what, what is your research sort of looked at? Yeah. So this goes back. So we did, I saw the paper you sent. That's, that was one of the clinical studies we did. We've done a couple more controlled feeding studies where we've looked at. Sort of. So that one was, I think the, where we saw middle-aged adults.

52:31
that were attending a clinic where they either were prescribed a ketogenic diet or a low-fat diet. And then we looked at sort of over time, we did DEXAs on them to look at like changes in body fat distribution, and we did C-selective depletion of the abdominal fat central adiposity. So we did that on the heels of a couple of other studies that we did that were controlled feeding and not necessarily clinical.

52:58
Yeah, so we did, and this was one of the first trials I worked on. It was a weight maintenance study over two months where we did a high versus low glycemic load diet that was, it wasn't like very low carb. It was probably 40% carbohydrates, so still pretty high. So in gram amounts, and again, obviously this is going to change individual to individual. Yeah. Is it what, around two? It was a lot.

53:26
over 200 probably, depending on their energy needs, you know, because we clamped it at the percentage. So it's going to vary in the grams. But we found that in two months, the participants without weight loss on the low glycemic diet lost, I think it was 15% of their visceral fat. And that was measured by CT scans. So specifically that fat that's around the organs and the abdominal cavity,

53:57
We were like, where the fat? Yeah. And so is that like, obviously significant, but is that like in absolute amounts? Is that quite a change in what you can see? Yeah. Well, what's interesting, so like, you know, relative to total body fat, the visceral fat cavity in that age group is like, it's pretty small when it's talking absolute amount. But, so they didn't lose weight. So we...

54:23
speculate one scenario that could be true is that they are technically redistributing that lipid somewhere to more metabolically healthy depots because of the diet, because insulin's down, potentially affecting inflammation and a bunch of different things. So that was one study we did. And then another one we did that was controlled feeding with the same diet. So low glycemic, high glycemic.

54:50
controlled feeding, this was a crossover study. So all the women consumed one diet for eight weeks and then switched to the next diet for eight weeks. And again, we measured like beta cell function, insulin sensitivity, the body fat distribution. And we found with the low glycemic diet, the women selectively depleted their visceral fat, their intermuscular fat was depleted. And then also that low glycemic group retained lean mass, whereas the high glycemic group lost lean mass.

55:19
And again, this is weight maintenance. So it's just like the change in body composition and fat distribution. And then also we saw improvements in insulin sensitivity and beta cell function in response to the low glycemic diet. And it was really doing those two studies that kind of set us down the path of looking at more restrictive carbohydrates diets. So we did the low glycemic and then followed that up with several ketogenic diet studies looking at how that affects body fat distribution.

55:48
also beta cell function, insulin sensitivity, and all the metabolic outcomes in different populations. Yeah. Did you find an enhanced response? Yeah. Well, so what's interesting about it, the one study we haven't published yet where it's designed to be weight maintenance, so we haven't published that yet, but the one we did with ketogenic diet in older adults, with a ketogenic diet, it's so hard to weight maintain somebody.

56:15
on the diet and they lose weight. So it's virtually impossible to keep the body weight maintained to look at specifically if there's some unique effect of the low carb, high fat, and the absence of weight loss. Because the one older adult study we did, they lost tons of weight. They did deplete a lot of visceral fat and a lot of intermuscular fat, improve their insulin sensitivity as you expect.

56:41
retained their lean mass. So that was, we published that study several years ago. But, you know, that was one of the ones where we didn't control the feeding though. So with this new study, we're hoping that like providing the food could actually, hopefully we can weight maintain them and see what happens, you know, in the absence of... Yeah. And do we just think that if you're going to lose weight at the same time, it's going to be more potent sort of effect?

57:09
Yeah, it's possible, right? So I think in the real world setting, people, you know, weight loss is a good outcome, right? But when we're like, when it's an experimental question, that we're trying to like, answer a scientific question instead of like, implement it. Yes. We kind of want our condition to be, you know, achieve that weight maintenance and that control. Yeah. Yeah, so interesting. And you know, I think when you talk

57:38
Like because of course out in the public and social media when we're talking about weight loss, which I know actually you're not trying to make or maybe healthy diets, maybe healthy diets is a better way to sort of put this. Then there is arguments for, you know, you know, as long because the calories, the most toxic. Um, part of the diet. So as long as you're in energy balance, then health should just, you know, your health should be fine. But from what you're saying, if maybe if people do.

58:08
they are still in weight maintenance, then maybe it's not the calorie per se, but it's where the calories are coming from if they've got metabolic issues. Oh, yeah. Yeah. It's so hard to tease apart. I think because certain diet patterns just put you at greater risk of being in positive energy. So it's hard to tease all these things apart, because one thing affects the next and a diet that's sort of...

58:34
bad for your metabolic health is going to make you more hungry, is going to affect the way your food choices and it's going to affect a lot of things in a real world setting. I think the hunger part, the way a diet affects appetite and hunger is a huge consideration. It's all very interesting. Yeah, I agree.

59:03
I mean, now very quickly, because I don't think this will take much discussion anyway, but I am a fan of not French fries per se, but I do like a pub chip, you know, a nice big thick pub chip. And so I was really intrigued by your study that looked at, hang on, what's going to happen whether or not we eat French fries versus almonds, for example. I know. I love this study. This was a very, you know, an interesting study that, you know, I was not a lead on this one.

59:33
I was fortunate enough to get to be a part of this team. So David Allison and Daniel Smith were the PIs of this particular study. But it was sort of wanting to prove, there were so many epidemiological studies coming out saying potato consumption was such a major driver of obesity and weight gain, right? So with like increasing servings of potatoes per day, you were increasing your likelihood of having obesity. And really like,

01:00:02
There's so many problems with sort of singling out individual foods like that when it comes to looking at how food affects health. We know it's an overall dietary pattern, right? You can't really kind of demonize one food in particular. So, we designed a study. David Allison has done so many studies like this where you take a myth, what you would consider...

01:00:26
something that is sort of accepted as something that drives obesity, whether it's like not eating breakfast or things like that and sort of actually designing a randomized clinical trial to test it, right, to see if it's actually true. So

01:00:41
they had the idea that we would do a randomized clinical trial and actually feed people French fries every day to see if it affected their body weight and their fat mass. So what's interesting, almonds are widely considered a health food, that eat almonds instead of these other things. So that was our control. And then so they fed, had people eat French fries every day for, I think it was three months? Yeah, I think it was three months.

01:01:11
to look at changes in- 30 days. Yeah, yeah, yeah. So yeah, so you know, they found that these, so I'll say this too, a lot of these folks were healthy. A lot were college age students that were like on our college campus. So they were healthy folks, right? But what we found that there was no weight gain, right? Over these 30 days from eating fries every day, which is an interesting outcome, right? Yes.

01:01:39
But it didn't differ from the folks that ate almonds every day as a snack. So I think, you know, what that kind of spoke to is that some people, you know, you can feed them these types of things and they do compensate calorically. They didn't eat something else because they ate the fries. So that it's just like a very unique question that no, and these people, the fries did not cause them to gain weight. Yeah. And did you know, I found it interesting because.

01:02:05
you know, as a nutritionist and, you know, and it's interesting in terms of macros, like I have, I only really got interested in macros maybe three years ago, even though I've been a nutritionist for like, you know, 25 years. But in my head, I used to catastrophize things like enjoying every once in a while, like I say, okay, every week, all right, you know, fries at a pub and I would completely avoid them because of that kind of

01:02:34
belief, I suppose, that there are just going to be certain foods that are going to be uniquely fascinating compared to others. Right. That's an important point, yes. We talk about these dietary patterns and I think the background of all of that is you still have to enjoy food, right? Like you said, if you want to have fries or chips, you know.

01:03:01
as a part of like your diet, you know, it's just important to keep in mind, like, to not be too restrictive, like allow yourself to do those things, but also keep in mind like what you're doing, maybe 80 or 90% of the time probably needs to be look a different way, you know, 100% yeah. What is someone's what does someone I follow someone in there like there are no there are

01:03:24
There are always trade-offs. I don't know. In nutrition, there are always trade-offs. And so if enjoying makiki fry means that I miss out, that I just decide, choose not to have cheesecake or whatever, actually that's fine with me. Yeah. Cause that's a pattern thing anyway. Right. Exactly.

01:03:45
Amy, you're involved in so many interesting studies and I'm really looking forward to sort of following along with your research as it unfolds. Can you let us know where we can find more about your research and your studies? Where's the best sort of port of call? Yeah, so we are currently about to release a website called Diet for Diabetes. It's affiliated with our UAB.

01:04:13
page, but it's an independent URL. It's just like, I think it's just dietfordiabetes.com, I think. And so it's going to go live here shortly. And it has information about past studies, ongoing studies. We put our publications there. You can see information about our team. And then also, I do have like a Twitter that I try to...

01:04:37
push out publications as they come out as well and like new grant funding and stuff like that. I'm not great about it, but I try to do it like remember to do it as much as possible. And that's at Amy M. Goss. And then I also have an Instagram where I'm posting some things too that I recently started. So that is awesome. Yeah, that's at Dr. Amy Goss. Dr. Amy. That's lovely, Amy. Thank you. I will put the links in the show notes. And that.

01:05:04
website will be super interesting. And I think also for people who might want to have, you know, if they go to the doctor and they've been looking for solutions, like even them alerting their doctors to, to, you know, these types of resources is just great for that. Yeah. And we're going to try to post sort of menus and information about the diets that we're using in our studies as well. And then also we eventually will have like a virtual

01:05:34
um, counseling option with our study, with our dietitians on staff too. That is so great. This is a lot going on. That's amazing. Amy, thanks so much for your time this morning. I really enjoyed chatting. Thank you so much for having me. This was great.

01:06:02
Alrighty, hopefully you enjoyed that. I certainly really enjoyed chatting to Amy and I'm really excited about the future of this space with regards to the types of trials that her and her team are running. Next week on the podcast, I have back on the show with me my really good friend, Michelle Matangi, all about mindset and her new course to help people get to the bottom of their resistance when it comes to weight loss and their success in this space.

01:06:31
So I don't doubt that you'll look forward to that conversation. Until then though, you can catch me over on Instagram, Twitter, and now threads @mikkiwilliden, Facebook @mikkiwillidennutrition, or head to my website, mikkiwilliden.com where you can book a one-on-one consultation with me. All right guys, you have a great week. See you next week.