#615: Why Processing Doesn't Determine the Healthfulness of Plant-Based Diets – Alysha Thompson, PhD

0:00Hello and welcome to Sigma Nutrition Radio. This is episode 615 of the podcast. My name is Danny Lennon and you are very welcome to the show. Today we're going to be discussing a set of really interesting and often debated topics within nutrition science at the moment through the lens of a recent paper that was published that sheds light on some of these questions. And I think, as we'll see, there are many interesting questions embedded within the original research question. And so we're going to be taking a look specifically at a prospective cohort study that was titled Plant-Based Diets, Ultra-Processed Foods, and Risk of Mortality and Major Chronic Diseases.

0:41And so to walk through not only the paper, which is really interesting in and of itself, but some of the larger implications and some of the bigger research questions that it relates to, I'm going to be talking with the lead author on that paper, Dr. Alicia Thompson. Dr. Thompson is a research fellow at the Co-Center for Sustainable Food Systems and Institute for Global Food Health at Queen's University, Belfast. She has a PhD in nutritional epidemiology, and most of her work relates to working with large prospective data sets. For example, today we'll be looking at her work that used the UK Biobank, and she's involved in a range of work that relates to plant-based diets, flavonoids, and how some of these things connect to chronic disease risk like type 2 diabetes, cardiovascular disease, cancer, and kidney-related outcomes.

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2:41So with that out of the way, let's jump into this conversation between myself and Dr. Alicia Thompson.

3:02a very big welcome to the podcast to dr alicia thompson thank you so much for taking the time to come and talk to me thank you thank you for having me it's great i think as i mentioned to you as i'm sure we'll get to a bit later on after reading one of your publications i thought not only It was an excellent paper that we'll talk about, but also raises some really important points that are big topics in nutrition science at the moment. And so it's a good gateway into those types of conversations. But before we get into any of my questions, can you let people know a bit about your work, your research interests, anything else you think might be relevant to them?

3:35Thank you for having me here, Danny. My name is Alicia Thompson, and I'm a research fellow at the Co-Centre for Sustainable Food Systems at Queen's University, Belfast. And broadly, my work is within nutritional epidemiology. So I'm interested in how habitual dietary patterns relate to long-term health outcomes, particularly chronic diseases like type 2 diabetes, cardiovascular disease, cancer, and also mortality. So a lot of my work thus far has been on plant-based diets, but really trying to move beyond the simple question of whether someone eats a plant-based diet or not. I'm interested in the quality within the plant-based dietary pattern because two people can have very different plant-based diets.

4:21They eat quite different foods nutritionally within that as well. Alongside that, I've also worked on flavonoids, flavonoid-rich foods, which fit quite naturally into this area. So foods like tea, berries, citrus fruits and other plant foods that contribute to a range of bioactive compounds. and we're interested in how these patterns are also associated with better long-term health. And then more recently, this paper on plant-based diets and ultra-processed foods has come about. And again, we're just again delving into the area of plant-based diet quality and what contributes to this. So yeah, that's a sort of quick overview of my work so far.

4:59And as we'll get to this prospective cohort study that you've published, There's a lot of really interesting layers beneath it, as I'm sure I'll get to a bit later on. But from an overview level, when we're looking at not only this healthfulness of plant-based diets, but this interaction then with, in this case, a classification of ultra-processing or not, can you maybe lead off with, for you, what was the research question that you were trying to answer that went behind the design of the study in the first place? Yeah, great. So essentially, yeah, a lot of our work has looked at plant-based diet quality previously.

5:33And then obviously with this increasing trend of looking at ultra-processed foods, we thought, how does this fit in the context of a healthy plant-based diet? So our main question essentially was whether ultra-processed foods or the content changes or influences or modifies the association between plant-based diet quality and long-term health outcomes. So I would frame the study as setting the intersection of two active areas of nutrition research. So the first being plant-based diet quality, where the literature is increasingly showing that healthier plant-based diets are associated with better health outcomes and that quality does matter.

6:12A diet can be plant-based, but still quite different in nutritional content. A diet which in whole grains, fruits and legumes is quite different to one that's higher in refined grains and sugar-sweetened beverages. For example, the secondary of ultra-processed foods is growing in evidence, linking UPFs to adverse health outcomes. And we wanted to better understand how this fits in the context of plant-based diet quality. So is it the processing itself? Is it nutrient profile, energy density, palatability? There's so many different components and drivers of this group. So yeah, our question deliberately was more nuanced than are plant-based diets healthy or are UPFs harmful?

6:55We wanted to know whether the UPF content of plant-based dietary patterns influenced the associations with mortality and major chronic disease risk. And I'm sure as we'll get to much later on in this conversation, even that raises a whole host of other questions that are really interesting to consider in the fact that not only are we considering now healthfulness as this broad concept, and we can think of more healthful or unhealthful versions of, let's say, a plant-based diet. Now it ties in the question of if people are interested in this ultra-processed as a label, based Nova or not, is that the right way to make that demarcation between healthful or not?

7:34And so I'm interested to ask you a bit about that later on. But to give people the overview of what the study actually looked like, can you maybe walk us through the main elements of the study design, how you went about that? And then as we do that, maybe some explanations for why it was designed in the way it was. Sure. Yeah. So this was a prospective cohort study that we use, the UK Biobank. I think a lot of people are familiar with the study now. It's widely used across the world. So we assessed diet first and then followed participants for all-cause mortality, type 2 diabetes, cardiovascular disease and cancer.

8:10So I call that the core four because we've done this a lot in my research anyway, looking at these four core endpoints. So again, the study used the UK Biobank. It's a great resource, a great prospective study. And it was based in the UK. It recruited over half a million study participants between 2006 and 2010. And for this analysis, we included participants aged 40 to 70 years old. So it's a middle-aged adult cohort. And participants in our analysis were included if they completed at least two 24-hour dietary assessments. So the thing with the UK Biobank is that Great Resource recruited half a million people.

8:51And at baseline, all study participants completed a baseline assessment, which included completing various touchscreen questionnaires, providing biological samples and imaging, for example. However, in the touchscreen questionnaire, they asked several questions on diet and lifestyle. However, the dietary questions were very basic and minimal. And this was a food frequency questionnaire, and I think it covered 21 questions on diet. So this was very minimal, not very detailed for us to carry out detailed analyses. So a few years later, clearly researchers decided, oh, actually the dietary data isn't so great with what we have for all half a million participants.

9:34Let's implement more detailed and comprehend particularly chronic diseases like type 2 diabetes, cardiovascular disease, cancer and also mortality. So a lot of my work thus far has been on plant-based diets, but really trying to move beyond the simple question of whether someone eats a plant-based diet or not. I'm interested in the quality within the plant-based dietary pattern because two people can have very different plant-based diets. They eat quite different foods nutritionally within that as well. Alongside that, I've also worked on flavonoids, flavonoid-rich foods, which fit quite naturally into this area.

10:13So foods like tea, berries, citrus fruits and other plant foods that contribute to a range of bioactive compounds. And we're interested in how these patterns are also associated with better long-term health. And then more recently, this paper on plant-based diets and ultra-processed foods has come about. and again we're just again delving into the area of plant-based diet quality and what contributes to this so yeah that's the sort of quick overview of my work so far as we'll get to this prospective cohort study that you've published there's a lot of really interesting layers beneath it as i'm sure i'll get to a bit later on but from an overview level when we're looking at not only this healthfulness of plant-based diets but this interaction then with in this case a classification of ultra-processing or not.

11:01Can you maybe lead off with, for you, what was the research question that you were trying to answer that went behind the design of the study in the first place? Yeah, great. So essentially, yeah, a lot of our work has looked at plant-based diet quality previously. And then obviously with this increasing trend of looking at ultra-processed foods, we thought, how does this fit in the context of a healthy plant-based diet? So our main question essentially was whether ultra-processed foods or the content changes or influences or modifies the association between plant-based diet quality and long-term health outcomes.

11:36So I would frame the study as setting the intersection of two active areas of nutrition research. So the first being plant-based diet quality, where the literature is increasingly showing that healthier plant-based diets are associated with better health outcomes and that quality does matter. A diet can be plant-based but still quite different in nutritional content. You know a diet which in whole grains, fruits and legumes is quite different to one that's higher in refined grains and sugar-sweetened beverages for example. The secondary of ultra-processed foods is growing in evidence linking UPFs to adverse health outcomes and we wanted to better understand how this fits in the context of plant-based diet quality.

12:21So is it the processing itself? Is it nutrient profile, energy density, palatability. There's so many different components and drivers of this group. So yeah, our question deliberately was more nuanced than are plant-based diets healthy or are UPFs harmful? We wanted to know whether the UPF content of plant-based dietary patterns influenced the associations with mortality and major chronic disease risk. And I'm sure as we'll get to much later on in this conversation, even that raises a whole host of other questions that are really interesting to consider in the fact that not only are we considering now healthfulness as this broad concept, and we can think of more healthful or unhealthful versions of, let's say, a plant-based diet.

13:06Now it ties in the question of if people are interested in this ultra-processed as a label based Nova or not, is that the right way to make that demarcation between healthful or not? And so I'm interested to ask you a bit about that later on but to give people the overview of what the study actually looked like can you maybe walk us through the main elements of the study design how you went about that and then as we do that maybe some explanations for why it was designed in the way it was sure yeah so this was a prospective cohort study that we use the uk biobank i think a lot of people are familiar with this study now it's widely used across the world so we assess diet first and then follow participants for all-cause mortality, type 2 diabetes, cardiovascular disease and cancer.

13:52So I call that the core four because we've done this a lot in my research anyway, looking at these four core endpoints. So again, the study used the UK Biobank. It's a great resource, a great prospective study. And it was based in the UK. It recruited over half a million study participants between 2006 and 2010. And for this analysis, we included participants aged 40 to 70 years old. So it's a middle-aged adult cohort. And participants in our analysis were included if they completed at least two 24-hour dietary assessments. So the thing with the UK Biobank is that great resource recruited half a million people.

14:34And at baseline, all study participants completed a baseline assessment, which included completing various touchscreen questionnaires, providing biological samples, and imaging, for example. However, in the touchscreen questionnaire, they asked several questions on diet and lifestyle. However, the dietary questions were very basic and minimal. And this was a food frequency questionnaire, and I think it covered 21 questions on diet. So this was very minimal, not very detailed for us to carry out detailed analyses. So a few years later, clearly researchers decided, oh, actually the dietary data isn't so great.

15:14with what we have for all half a million participants. Let's implement a more detailed and comprehensive 24-hour dietary assessment. So this was called the Oxford Web Q dietary assessment, and it was issued three years after the initial recruitment. And it went on between 2009 and 2012. So for the course of about four years, up to five dietary assessments were issued to the participants. However, this was in a subset of participants. So this leaves us with around 210 ,000 participants who've completed at least one dietary assessment. So I find that a little bit disappointing because compared to the half a million people we could have been working with, we're now sort of brought down to that smaller figure, but a great resource all the same.

16:02So yet in this analytical sample for this study, we were left with just under 125 ,000. And this was because we restricted our analysis to those who completed a minimum of two 24-hour dietary assessments. And this was just to remove a little bit of the noise associated with one dietary assessment and how this may not capture a great idea of participants' habitual dietary patterns. So we included those who completed a minimum of two for that reason. So, yeah, the participants reported what they ate and drank over the previous 24 hours. and we averaged the intakes for the food items that we required for our scoring system across all five of the dietary assessments that were eligible.

16:46And after characterising participants' diets and following them using the linked health records, we then were left with the outcomes that we decided on, which were all-cause mortality, cardiovascular disease, type 2 diabetes and incident cancer. and our follow-up ranged from about 8.3 to 10.5 years depending on the outcome and our statistical analysis approach was using Cox proportional has regression models and these models were used to estimate whether people in the higher adherence group of the dietary pattern had a higher lower rate of developing an outcome over this follow-up period compared to those in the lower adherence group.

17:25Can you maybe speak a bit more for people about what you ended up having then for those dietary patterns at the end and that kind of interaction of both the nutritional quality side of it and then the kind of processing emphasis as well and where that left you with these different patterns. Sure yeah this is where it gets a bit complicated and actually if you take a look at the study it's quite mind-blowing there was a lot of different dimensions to this so to break it down simply hopefully we combined the two frameworks so the plant-based diet indices which were previously created and published by Harvard colleagues back in 2016 and we used this scoring approach the plant-based diet index or PDI as I'll probably refer it to as and we replicated this in the UK biobank so again using these this indice first and then we brought in the NOVA classification system to capture the processing level of the food items that were included within each food group included in the plant-based diet index.

18:23So that was crossing the two dimensions, which gave us four different dietary patterns. So this left us with a high UPF HPDI, a low UPF HPDI, a high UPF UPDI and a low UPF UPDI. And each score was characteristic of different healthier plant foods or unhealthy plant foods. and just to note that within this dietary pattern and within this plant-based diet index although this is a plant forward or a plant rich dietary pattern this is not omitting animal based foods at all so I think that's a bit of a misconception that's had whenever we talk about plant-based there are so many different types of plant-based diets and not all of them omit animal based foods and this was quite nice within this scoring approach is that we didn't have to exclude people who consumed or reported consuming animal-based foods.

19:20This included everybody, but the scoring system was catered towards positive scores for those consuming plant foods and negative scores for those consuming animal-based foods. And then this was broken down again based on whether it was an HPDI or UPDI. So this was how the scores broken down just to detail within the second dimension of the processing level we classified the foods according to NOVA we separated the foods into UPFs and non-UPFs or low-UPFs as we'll describe it because within this group we also include groups that are included for NOVA 1 to 3 so yeah for the purpose of the modified scores UPFs were NOVA group 4 and non-UPFs were NOVA groups one to three.

20:10So when we crossed the two dimensions, we were left with the four dietary pattern scores. So this meant that instead of only asking whether someone ate a more healthful plant-based diet, we could then ask whether the healthful plant-based diet dietary pattern was higher or lower in UPFs. And I think the important thing to mention here is that these are research indices. So a phrase like high UPF, healthy plant-based diet sounds quite strange in ordinary language, but technically it means a healthier plant-based pattern, whether the foods contribute to the score or classify as ultra-processed or not.

20:49So it doesn't necessarily mean that every UPF is healthy in this context. But I do think it raises an important point that I'm sure we'll get to later on, where now, particularly in a lot of mainstream messaging, we're seeing oversimplified messages of basically equating the amount of UPFs with whether it's healthy or not. And as we can see, there's a lot of nuance here that I'm sure we'll get to. One of the specific questions, just as you mentioned, the NOVA classification, and you mentioned the use of the Oxford WebQ as well, given when a lot of this dietary information would have been collected, and then the ability to go and then assess that, and then knowing some of the nuances, and there's still debate within the utility or not the utility but how we assess certain foods on NOVA if it's not specifically designed to do that it can be quite a challenge from a research perspective to accurately put it in one of those categories can you maybe talk about how you went about that and was that indeed something that was difficult to classify what people had reported eating back when that data was collected yeah sure that was definitely one of the challenges and limitations of the study.

21:55So again, a huge challenge with the work. NOVA is useful in some parts. So applying it to self-reported dietary data isn't always straightforward because these recalls often lack full product and ingredient level detail that we require in order to categorise these foods into NOVA group four. So foods reporting in large cohorts involves some uncertainty always, especially within the plant-based diet index as well across different cohorts it's just although we're trying to replicate there's no such thing as perfect so again participants report with the aid but they may not always provide details on the brand the full ingredient list preparation method or whether a food was homemade or packaged fortified sweetened and this is quite important for the upf or nova categorization so nova pacification only requires information about the extent and purpose of the processing and for some foods this isn't straightforward so for example fruits and vegetables or legumes are clearly not upfs and sugar sweetened beverages and or those drinks and confectionery type products are usually easier to classify as upfs because usually they are all in that category but some foods sit a bit closer to this boundary so we found that a little bit tricky when it came to some of the food groups within the plant-based diet index.

23:19For example, fruits. We couldn't classify any fruit item as a UPF in the UPF category. So this meant that later on in our adjustments in models, we had to adjust for fruit whenever we were looking at the sole dietary pattern of UPF. So this is another limitation of the study and something we just had to consider and we're very transparent about. So again, the classification involved a lot of judgment, a lot of subjective judgment. And I think this is what's seen across many studies that are applying the NOVA system to dietary data. Yeah, it's not unique in our study. It is a broader challenge of UPF research.

24:00And it just means that transparency and sensitivity are important in carrying out these sensitivity analyses to better understand how UPFs fall within this broader idea of diet and habitual diet. But it also means that NOVA shouldn't be interpreted as a perfect measure of diet quality. And I think this is where we have got a little bit mixed up in recent research maybe is looking at UPFs as a measure of diet quality. And essentially it is, but alongside or in parallel with other measures, I think that's important. And I think a balanced position would be that NOVA adds useful information about food processing, that traditional nutrient profiling may miss, but applying it to real world dietary data sets requires careful judgment and cautious interpretation.

24:50And I think sometimes the media grabs hold of that and runs with it. And I do want to return to that point later on, because there is much to discuss about not only that misinterpretation, but the implications and for not only research, but public policy going forward. But if we return to the study, so we've talked about this study design, these different patterns, and we can look at from a top line level, what were some of the main results around your kind of primary outcomes, as well as for you, any of the results that are important to raise to people or that stood out in some way? Some nice and interesting findings from the paper.

25:25So essentially the broad pattern was that healthier plant-based dietary patterns were associated with more favourable outcomes, especially all-cause mortality and type 2 diabetes, whether or not they were higher or lower in UPFs. And that's the interesting thing to note, is that we find these beneficial associations, regardless of whether the healthy plant-based dietary pattern was higher or lower in UPF. So more specifically for all-cause mortality, we find that higher adherence to healthier plant-based patterns were associated with lower risk. And that was true for both high UPF HPDI and low UPF HPDI.

26:04and the hazard ratios were very similar between the two dietary patterns when it came to risk of all-cause mortality comparing highest to lowest adherence groups. When we looked at type 2 diabetes, again, we found very similar associations but a little bit stronger in the strength of association. The findings for healthier plant-based dietary patterns were that we found this association with lower risk but the strongest associations were for the low UPF HPDI. So this also, again, emphasises that whenever the underlying dietary pattern and nutrient density is high, there is an additional benefit of low UPF diet in the context of type 2 diabetes risk.

26:48So although we find that a high UPF healthful plant-based diet showed lower risks of type 2 diabetes, we find a stronger association for the low UPF HPDI. So this association shows that there might be an additional benefit of consuming low UPF products in this context. Moving on to cardiovascular disease. So this was a little bit of a complicated finding and maybe one that people would question why. We found that the high UPF HPDI was associated with lower risk, whereas the low UPF HPDI was not clearly associated in fully adjusted models. This result sounds quite counterintuitive. So I would explain it by, I suppose, returning to what the high UPF HPDI captured.

27:38So this meant that participants were consuming higher whole grain intake, lower refined grains, sugar-sweetened beverages, sweets, desserts and animal foods. So we can propose or suggest that these more beneficial associations we see with cardiovascular disease risk were potentially driven by the higher whole grain intake that we see in the UPF category. So this covers breads, whole grain breads, these cereals like muesli and these oat-based cereals as well. So that's all we can propose right now because we haven't carried out additional or more mechanistic analyses to look into these specific associations.

28:20But that's what we can propose and that's what we found. When it comes to cancer, again, like many previous analyses looking at this endpoint, the findings were less clear. The healthier plant-based dietary patterns were not clearly associated with total cancer risk. Again, this might be because total cancer is heterogeneous as an endpoint. Different cancer sites have different causes and dietary relationships. So total cancer can mask site-specific associations. So maybe in future studies, it would be more interesting to look at different subtypes of cancer rather than total cancer overall. However, in this study, we didn't have capacity to do this.

29:01Following on from that, the flip side of these associations is also important. So less healthy plant-based patterns were generally associated with higher risk. So this comes back to the initial point of not all plant-based diets are equal. Just because you consume a plant-based diet doesn't necessarily mean that it's a healthy one. And so when we split it into healthy and unhealthy plant-based diets, we see differing risk outcomes in these large prospective cohort analyses. So, again, the main message here is not simply that plant-based diets are protective. It's the quality of the plant-based dietary pattern that matters strongly.

29:39Another analysis that's worth noting or another sort of section of the paper was alongside plant-based diet indices and NOVA classification, we also used a modified nutrient quality index or MNQI which we refer to it as in the paper and this allowed us to look at whether the high and low UPF versions of the plant-based diet pattern differed nutritionally. So this index included positive components like fibre and protein and less favourable components such as saturated fat, total sugars and salt. So it gave us a way of asking are these high and low UPF plant-based patterns actually very different in nutrient quality or are some of them more similar than the processing label alone might suggest so what was interesting was that both the high UPF and low UPF healthy plant-based indices had similarly high nutrient quality scores so you can see in the paper in figure two this is a really nice bar chart where we compare the nutrient quality of the high and low UPF PDIs and you can see that there's really no difference between the two.

30:49This helps us explain why high UPF healthy plant-based dietary patterns could still show favourable associations because of this underlying nutrient density of a healthy plant-based dietary pattern despite it containing UPF food items. it's not simply that a diet high and low quality it's more than simply a diet that's high or low in upf so looking at this nutrient density gives us an additional nuance and into this idea of plant-based diet quality and then on the again the flip side and contrast when we looked at the unhealthful plant-based diet indices these had poor nutrient profiles including lower fiber protein, calcium, vitamin B12, particularly in some of the lower UPF variants.

31:36But again, comparing the high and low UPF unhealthful plant-based diet indices, these nutrient profiles look quite similar between the two. So this was a really interesting finding. Although nothing complex or hard to carry out, it was just quite nice to see what does a high and low UPF plant-based diet look like when it comes to nutrient density so there's a lot to work through and i think the first thing people will see here is that if we are again there's nuance within each of these different outcomes and i don't want to reduce any of that but from an overview level we can see that perhaps it might be fair for someone to think if we are looking at those distinctions between the healthful and unhealthful patterns those are relatively straightforward and sit with what we know from wider literature as well, that those healthful plant-based patterns are consistently shown these associations with positive outcomes relative to the unhealthful versions.

32:33Where it starts to get interesting depending on the outcome is this question of whether thinking about the amount of UPFs or category 4 ANOVA foods adds any refinement to that or gives us any extra information than rather just looking at the nutrient profile or a categorization of a healthy an unhealthy pattern. And at least for some of those outcomes like diabetes, there could be some signal there. But again, there's still a lot of work to get to it. And you started doing some of that work to try and distinguish why we might be seeing that. So I guess from your perspective, given the various hypotheses that are out there, what do you think may be good potential hypotheses to explain these potential differences?

33:17And if they really are inherent to NOVA classification or not? And I realise that's such a broad, wide question, but feel free to go in whatever direction you think might be useful. Yeah, a really good question and complex to answer. So again, it's hard to distinguish what among the high and low UPF diets may be driving the association. But what we can say is that whenever we looked at the food group analysis, there were specific food group. So we broke it down to the food group level and we carried out several sensitivity analyses within this paper, including a subgroup analysis, breaking down each of the 17 food groups that make up the plant-based diet index.

34:02So what we found here were that there were specific food groups that drive these associations that we see. So coming back to a lot of the literature again and a lot of the papers I've published previously have shown the same thing especially when it comes to type 2 diabetes it's the sugar sweetened beverages that typically drive the adverse associations and it's the whole grains that and fruits and vegetables that typically drive the positive associations that we see with type 2 diabetes specifically but again it's quite a broad it's quite a broad message that we've seen in previous literature too when we broke down each of the food groups into their high and low UPF counterparts.

34:46And actually, again, it emphasises what we concluded in our paper was that high and low UPF whole grains were beneficial for these hard endpoints. The likes of meat was adversely associated, whether it was high or low UPF, especially for type 2 diabetes. We didn't find any associations for the likes of dairy, eggs. We found a beneficial association for fish in the high UPF category. So it was very mixed with the associations that we found in the end when we broke it down to food group level. But whenever we carried out additional sensitivity analyses, which were vast, we carried out a leave one out analysis again to emphasise which of these food groups may be driving these associations that we see, whether they're adverse or a positive association.

35:39And again, with the Leave One Out analysis, although these results were pretty consistent with what we saw in the main analysis, again, we found that when we removed sugar-sweetened beverages, this is what sugar-sweetened beverages seem to be driving a large part of the adverse associations or the positive associations because lack of sugar-sweetened beverages could have a beneficial impact on our associations. We also carried out additional sensitivity analysis looking at independence of associations from nutrient quality. So we adjusted for this modified nutrient quality index in our primary analysis.

36:20And again, our results were broadly consistent with what we saw in the primary analysis. We also looked at the ratio of low to high UPFs against the PDI scores to see whether higher UPFs against low UPFs may be, there may be some differing association. And again, there were no consistent associations with the outcomes and we carried out this additional analysis. We also carried out potential modification between PDI scores as a raw score and UPF intake to see whether the HPDI and UPDI was modified by total UPF intake. And again, we found no significant effect modification by UPF intake. We then went on another level.

37:09We looked at effect modification by sex and assessed through sex stratified analyses. We had consistent associations with our primary results. So again, we went through these different levels of sensitivity and subgroup analyses to really dive into and discover what might be driving these underlying associations. And it really just points to this basic message of there are specific food groups within a plant-based diet and within the NOVA classification system that do drive these associations that we see. And that's why it's important to not just look at the NOVA4 as one group in isolation, but to consider them alongside diet quality, alongside nutrient quality.

37:59Context is really important. Looking at the food environment. Why are people consuming these foods? I think we need to ask more questions rather than just taking it for face value. And I think that's what we have concluded from this paper is that there's so many more questions to ask and so many more analyses to be done to really pull this apart and see what more is there to do with NOVA diet quality that we can figure out and analyse. And before I return to your specific study to maybe one more question pondering on this utility of NOVA, because this is a huge debate within nutrition science right now, all the way from, in some cases, people who are very much on board with the use of NOVA for all sorts of things, to the other extreme of very, I would say, in good faith, putting forward very good points around maybe not only a lack of utility, but putting us even in the wrong direction, and then a whole host of opinions in between.

38:59And so we've seen some other work from various groups that has indicated some of the things that you've touched on where the level of processing or whether something is in category four or not doesn't explain differences we're seeing. And so maybe isn't refining that message. But then again, there's other people in that point to just these associations we're seeing with ultra processed foods and how can we completely negate this? And so foreseeably, there could be people coming across your study now and maybe listening here that have, depending on their belief or position, could try and interpret it in two different ways, right?

39:35One could be that, well, maybe whether something is high or low UPF still does give us this additive piece of information and we layer it in on top of some of this other stuff and it's useful. where someone else might interpret it to say well really is it adding much more than once we know the food groups that determine healthfulness or not and we account for those and we know that's going to be driving much of these associations what foreseeably could be in a plant-based diet that would fall into this healthful pattern but still is high upf that is going to cause a problem or vice versa we could point to examples where that's clearly not the case right and on an individual food level.

40:16And so given that there's these different types of interpretations, at least from the data you've put forward, what do you think is the fairest interpretation people should come to? Or which one of those ends of the spectrum, let's say, do you find yourself falling more towards? Really good question. And yeah, there seems to be two sides at the moment, but with what we were trying to understand with this paper was a very neutral story. And I think that's what is shown with the paper with our interpretation I suppose and really what we want to conclude is that whenever the underlying diet quality is high UPFs can fall into a healthy dietary pattern whenever this underlying diet and nutrient quality is high I think that NOVA can provide useful information but I don't think it should be used alone it's a useful lens but not a complete measure of diet quality.

41:14And it's maybe, again, as I mentioned previously, it's maybe being used that way. But again, there's limitations to every study. But its strength is that it does capture something traditional nutrient profiling often misses. So that's what was interesting in our study, that we could then split these UPF, high UPF and low UPF foods according to the food groups that are present in the plant-based diet index. So that was a nice nuance to the paper however coming back to the limitations of the study trying to split these food items into how they are actually categorized as UPF is quite tricky when we don't have the formulation information the ingredient information we have a basic 24-hour dietary recall and that's what we're working with and our output is only as good as the input so I think that's important to emphasize that we are just using the dietary data that we're being provided with and that's the best that we can do.

42:12So that's why it's important to keep running additional analyses, asking more questions in this area and I think for nutrition research NOVA can help us ask questions that nutrient-based approaches may miss alone and for public health I think it can help describe patterns in the food supply and identify how industrial or industrially formulated foods contribute to population diets, but its limitation is that NOVA groups together foods that may be very different nutritionally. So again, a sugar-sweetened beverage or confectionary product is very different in fibre, protein or saturated fat. So my position would be is that NOVA does not explain everything and NOVA is not useless, but the useful question would be is what does NOVA add beyond nutrient quality, food groups and dietary pattern analysis and when does it improve our interpretation of diet disease relationships and I think these are the key questions we should ask when running these analyses and breaking these analyses down.

43:15Great point and I think that refers to what you'd previously said about many of these questions we still need answers to because NOVA may be picking up something but right now we actually don't know what that necessarily is. And as you said, we have these really heterogeneous groups. And so really we're bucketing things together that maybe isn't the case. If we're saying it's down to the degree of processing, well, there's other ways to assess that don't take into account the intention behind it. And so maybe we need a different way to assess that. But lots of really interesting open questions.

43:44I did want to return to one thing about your particular study, because as in any of these cases, when we see a prospective cohort study, the way that adjustment is done for a number of these factors is crucial and you guys did a really nice job on some of this covaria adjustment can you maybe talk a bit about that how you went about that given the complexity of the exposures that we're talking about here this is a complicated point and something that our group does have a lot of experience in and we have looked at these endpoints previously when it comes to plant-based diet quality but again when we're pulling in this additional dimension of ultra-processed foods, that's when things change a little bit.

44:23So we adjusted for a wide range of socio-demographic lifestyle, health and dietary factors to reduce this confounding that we talk about, while recognising that some variables can also sit partly on the causal pathway. So in, again, observational research, as many of your listeners will already know, people with different dietary patterns often differ in many other ways. People with healthier diets may be more physically active, less likely to smoke, have different educational or socioeconomic profiles or drink alcohol differently, use medications differently or have a different baseline health status.

45:03And those factors can really confound this diet disease relationship or associations that we see. So we adjusted for this broad set of covariates based off of a literature search and we update this literature search frequently because we're in the area of research and the papers are coming out vastly all the time and we have to keep up to date with what covariates are important when it comes to our endpoints and our exposure. So we adjusted for the key confounders in addition to the likes of medication use or polypharmacy, long-term health conditions or multi-morbidity, the number of dietary assessments that were completed by the participants because again someone who has completed all five dietary assessments is probably more interested in their health.

45:51So these were other confounders that we had to consider but also it's an important point to make and one that we have made in previous studies is the mediator question and this is more nuanced again and in previous studies we have ran mediation analyses. It would have been quite nice to actually run mediation analyses in this paper too however for capacity reasons. It just would have blurred the lines and possibly made the paper a little bit more hard to interpret than it already is because of the different layers and dimensions of the scores. So this mediator idea, it's something that may lie on pathway between diet and disease.

46:31And BMI is a great example for this as it's typically this mediator, it plays this mediator role and it can confound the association because body weight is related to both diet and disease risk but it could also mediate the association if diet influences body weight and body weight then influences type 2 diabetes or cbd risk for example so this means that adjusting for bmi in our case probably attenuated the associations and may have produced more conservative estimates if part of the effect of diet operates through body weight and this is the same conceptual issue applies to lipids inflammation glucose metabolism or other biomarkers depending on the research question and timing however mediation in this case for our paper wasn't wasn't part of the question or hypothesis so bmi was considered as a confounder alongside the other health lifestyle medication confounders as well that's really useful and i think it's something that people can keep an eye out for when reading Annie paper that this concept of confounders and knowing the difference between that and these mediating factors, but not only that, how that connects to the actual research question.

47:41And as you perfectly put it, that in some cases, depending on that research question, it would be categorized as this confounder and we have to adjust for the, maybe in another situation, we may not do that. And so understanding that particularly in such a complex exposure that we have, and especially when we're looking at chronic disease outcomes that are again complex as well to to look at trying to get enough control from appropriate adjustment without over adjusting is this fine balance so you guys did a really nice job of that so alicia when we think about where this work then leaves us from some of the takeaways that you not only had from that but then those other research questions that it maybe opens up that either you have planned for your group to do or maybe you'd like to see other groups take on what do you think are some of those pertinent next research questions that over the next couple years hopefully you can start to see some work try and answer yeah so i think it's a really exciting space now in nutrition research despite the upf story and narrative being taking over a little bit there's so much more to look at and there's so much depth in that too so i think future research needs to move beyond the broad labels especially for plant based diets we need more detail on quality nutrient adequacy processing level affordability and substitutions i think that's a really interesting area now although it's quite a it's not a new thing substitution analysis i think it's coming back i think we see these trends in nutrition these different areas come back again and again so for upfs i think we need to look at subgroups rather than total upf intake alone and this these analyses are coming through now in the literature.

49:22I think, yeah, that's one clear direction. I think total UPF intake is useful, but it can hide this heterogeneity, you know, that we see across the different food groups. A second direction, substitution analysis. I think in nutrition, the comparator really matters. And if someone reduces one food, what are they replacing it with? And that's the key question. And that's just, that's real life context that we're maybe missing a little bit in nutrition science at the moment. The third direction is nutrient adequacy. I think in our nutrient data or dietary data, we need to consider this nutrient element.

49:57I know nutrients are now old-fashioned and we're looking at whole foods as one and dietary patterns, but I think nutrients play a key role in addition or in parallel to these dietary patterns. We need to look at how these dietary patterns actually, how they look when it comes to nutrient adequacy. fourthly I think we need to point in the direction of applying these analyses to more diverse populations and I think again us researchers are saying this all of the time we much of the evidence is coming from the high income predominantly white cohorts and we need research across different cultures food environments socio-economic contexts and types of plant-based products as well the food environment has changed massively especially from a lot of these this cohort data the dietary data that we're using which for example in the UK Biobank was reported between 2006 and 2000 or 2009 2012 the food environment has changed drastically since then and that's another limitation of applying this nova framework to this old dietary data is that our food environment is very different now and this data maybe doesn't capture this UPF framework that we are trying to apply it to.

51:13So that's a challenge in itself. I think we'd also like to look on a deeper level, especially within our group, we also look at which of the components of a plant-based diet or a healthy dietary pattern may be driving these associations, not just on a food group level, but on a compound level. So looking at polyphenols, more specifically flavonoids, our group does a lot of work into flavonoids and different health outcomes and has done so within the Harvard cohorts and UK Biobank. And this is just another level. And I think what would be really interesting now is to pull in the omics. What does your protein signature look like?

51:51This proteomic signature, biomarkers. I think there's so much more than just diet. I think we can look at this underlying biological, these underlying biological mechanisms too. And I think there's so much more in this area to discover. And it's quite an exciting space at the moment, especially with the high quality data that we have access to and can work with. Absolutely. As you said, there's no shortage of really interesting research questions. And I think there's lots of groups doing some really nice, elegant work on that. So hopefully the next couple of years, we'll continue to see more excellent work answer some of these questions.

52:26Before I get to the very final question, Alicia, for people that are listening, is there anywhere you could send their attention towards if they want to learn more about you or your group or any of the work that you guys are doing? Yeah, sure. For my work, I mostly keep LinkedIn up to date. I try my best posting papers that we've published recently. If you want to look at some of the Co-Centre for Sustainable Food Systems work, which covers not only nutrition, but the whole food systems, which is also important and something that obviously we don't have enough time to talk about today, but another area of research that I'm also looking into with regards to healthy and sustainable diets.

53:03If you want to point listeners to the Co-Centre for Sustainable Food Systems website, that will keep you updated with what we're doing in Belfast and what's going on here and all of the exciting things to come. So that will be linked up for everyone listening in the description. And of course, I will link to the study that we have discussed throughout this episode today. I highly encourage you go and read the full text of that and go through that in more detail. So with that, Dr. Alicia Thompson, we get to the very final question that I always end the podcast on, which can be completely outside of what we've discussed today.

53:35It's quite a broad, open question. So apologies for putting you on the spot. But it's simply, if you could advise people to do one thing each day that might have a positive impact on any area of their life, what might that one thing be? Oh, wow. Through me. You've thrown me now. Let me see. So I think not related to nutrition or work. Let's keep it away from that. I think, to be honest the the secret to a good life is realizing how good it already is so that's something i like to live by look up be thankful and don't worry too much fantastic a perfect way to round this out dr alicia thompson thank you so much for first of all giving up your time to come and talk to me today for the excellent explanations you've given and more so for your wider work and the excellent work that you're doing so thank you for that it's really been a pleasure thanks so much

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