Distinguished Colloquium Speaker Series

Description of the video:

Thank you for coming and it's bed to see you. It is truly a privilege and honor and a special treat to introduce today's guest. And you know, these introductions, I don't want to read someone's CV. You can read it. I'm sure online. You can go to Link and find out where he got his degrees and all that. But I think giving a sense of the person as a scholar and we have a wonderful scholar, and as a leader, and we have a superb and as a human being, M. Good introduction. And this point is because this is an exceptional person. I've had the privilege of knowing doctor Passacos for at least a year or so now since he joined the NIH as the director of the office of dietary supplements in 2022. This is closer to two years. The field of science is one that many personalities make important contributions in different vantage ones. There are those who enjoy the beauty of exploring ideas, perhaps most typified by the mathematician, G Harding, who in his day was the preeminent mathematician who probably seen his character played by J Jeremy Irons in the movie, the man affinity. And he prided himself and wrote in a mathematician's apology that he had never done anything useful. And he thought that was important because he said useful mathematics is of I only look on things that are beautiful that are just about the ideas. It's actually not true that it was not useful. He came up with among other things, party win book equilibrium, which is one of the most important things used in the field of genetics. But it was so simple mathematically for him that he published it in science, not a math journal because he was embarrassed that math friends would see this very similar thing he did. That's sort of the selfish view of science. Let me just indulge. It's not necessarily a bad thing because brilliant things have come out. Right Newton indulging and coming up with Optics and the calculus and the universal law of gravitation in his spare time. People who've indulged have done great things, but there's another side science and it's science that recognizes the surface to others and the immense responsibility we have not just to get our protocols, IRV approved for ethanol standards. But to accept stewardship of privilege we given funds b, which all come from taxpayers like my mom and your mom and dad and so on, who pay their taxes, not so we could be famous, so we co sit around and scratch our heads, but so that among other things, we can make contributions to the betterment of humanity. And we see that in nutrition science for a long time, the Spirit of Florence Nightingale, who many people think of as a nurse. But in fact, was also a nutrition scientist who recognized that soldiers died more often for infection and hypothermia and malnutrition than they did from bullets and bombs. And she worked on that and she became the first woman member of the royal Statistical Society. She was a statistician and theologist and nutrition scientist advocated for good nutrition for military nursing. It was Widowson and McCants, a very famous scientific team who nearly killed themselves in the early 20th century, experimenting self experimenting with ingested food documents. To protect again the military and the general public so that they could prepare the healthy diets for the UK population during work. We could go on. There are many who have seen that fall to duty. At 20 years ago, little after 911, who was a young man in Connecticut, and he was working in his father's restaurant and learning how to run things. As any of you who have ever been in or seen or worked in a restaurant? No. There's a lot of moving parts, and there's a lot of knowing how to make things happen in a restaurant. Then something else happened in the world. That was 911. That young man felt called That young man who had been to college in appreciable way at that point, said it's time to go. It's time to make a difference in the world, and that young man went to college, go, from there went on to graduate school. And from there joined the Native Army Resource Center as the director of programs. That young man was doctor Stephane Asia. And he worked there for years and understood operations and his restaurant experience helped him understand how to get state and done. And he understood the intense Responsibility at a still a very young person with a budget bigger than most of us will ever oversee. That budget had to be used well for the protection and service of our military personnel and protect would serve us. From there, he said I'm going to protect American Public further and advanced science further, Joint NIH as the new director of the Office of Dietary Supplements when doctor Paul Cokes, who many of you know, because he's on our Agile faculty, retired from acquisition, doctor Pasi He is known as a great scholar himself in the area of protein energy requirements, amino acid, metabolism and effects, muscle injury, prevention, rehabilitation. And we are very lucky to have rescue. Analysis. You do that every morning. I think my days would be more motivated and that was outstanding. Thank you so much. Really thank you for the opportunity to come out today. Share a little bit about what we're doing at the Opposite Dietary Supplements and take you give you a story, a story that the analys already shared about why this topic is important. Why I chose the route I chose, and how did I end up here and why is rigor reproducability and transparency so important, I believe in the field of dietary supplements. I hope you do that today over the next 45 minutes or so. So we'll go over a little bit more about my introduction and overview of the office. Because it's important for many of you, if you're not aware of what the office of Dietary Supplements does, I want to show you that today. But more importantly, I want to show where we're going. O the last year, we've put all of our time and effort in redesigning and reorganizing the office to be more flexible, adaptable, more agile to be able to respond and urgent demands. I want to spend a little bit of time about focusing on what the office has done in terms of product integrity. That's one small piece of rigor reproducibility and transparency. Then shift ears a little bit and talk about the current state of trust and the limitations associated with dietary supplement science. All of that to say that our office is now putting together a new initiative called reproducibility and integrity guidance, optimize research for dietary supplements or more athlete called rigor. That's a new initiative that we're getting up and offering. So you heard a little bit about this. My path is very similar to many of you. Yes, I went through, undergrad, master's degree, PhD. But I did so after years of running small businesses, and I understood the importance of accountability. Understood the importance of setting the example. When I got out of school, I took those principals with me and joined the army as a medical service officer in the US Army Medical De They assigned me to the US Army Research Institute, Environmental medicine, and if they didn't, I had no idea what I was going to do. I draw my eggs in one basket the user because I was dead set on using the skills that I acquired during graduate school to apply those to address questions specific. During that time, I've had the opportunity to run studies all over the world. A variety of military installations here in the US overseas with our NATO partners on top of mountains in cold weather operations, where you have no access to anything but so. It was a very good experience where I've got to take what I learned in the laboratory and apply it all over the place to try to answer important questions for the service. So my research really focused on protein requirements. Specifically, protein and amino acid requirements to support recovery and minimize muscle mass loss in periods of extreme stress and in the environments in which our service members are operating. They typically don't operate in a gym. They don't operate with plenty of food around them. They operate in austere locations with very limited access to food, and those conditions can precipitate seminal muscle loss and also physical and functional decline. And we don't want that to happen. We have this term in the military sure your husband is aware of readiness. A soldier needs to be ready to perform at any point. And when they can't, that's a big problem to the army. Our job as military nutrition scientists is to use nutrition and what we know about metabolism and molecular biology, to develop interventions that offset those declines. A lot of the evidence that we generated over the next 15 years led to policy updates and also combat rational development. So in 2022, I was a chief of the military and Performance Division. I kind of switched gears. I was leading a division of about 90 individuals, about 30 PIs, whose mission it was to design Appropriate and accurate and valid interventions to mitigate musculo skunal injury risk in soldiers. And one of the biggest issues in the military is soldiers constantly become injured. The trip from the army right away from basic combat training that has a loss in terms of finances and also a loss of personnel, and they become injured more and more and more over time. You can see the snowball effect that might have on an individual's career and the subsequent health care costs that places on the VA, and the external system wants to get out of service. But in May of 2022, I got an e mail from the search committee chair for the Office of Dietary Supplements Director position. And I was kind of intrigued. You know, I am a nutrition scientist, dietary supplements wasn't necessarily my spin, but I did work in the context of dietary supplements in the form of amino acids. And I saw this as an opportunity. What really bothered me about my field is that no matter what you say in your paper, no matter what you say in a presentation, and get misconstrued and used as saying that I am all for this or I am all against this, and this is going to cure everything you have or this is snake oil it's not going to work whatsoever. I felt that this was a unique opportunity to come in, bring a level of objectivity to the office dietary supplements and really hold in on key issues of importance to public health and drive objective and strong science forward. So after a year or so, I got the offer and lo and behold, I'm here. A lot of change has happened over the office since I've been on board, and I'll share a little bit about that today. So the history of the HF and dietary supplements, it was formed in response to a law. So in 1994, there was a Dietary Supplement Health and education Act. That act was an amendment to the Food Cosmetic Act, which really said that dietary supplements are now going to be regulated as food. Now how that actually happens is that the FDA is associated with the regulatory policies of dietary supplements. They do have certain forms of regulation. They certainly don't have the regulations associated with pharmaceuticals, but they are regulated in the context of food and food ingredients. We on the other hand, the partner office to FDA's Office of Dietary Supplements at NIH, our job is to promote dietary supplement science and do so making sure science that is being done is of the up utmost quality so that the public can have credible evidence that they can make the right informed decisions about dietary supplement use. NIH is huge. I don't know how many people if you have seen the campus. Is the college campus in and of itself. There are 27 institutes and centers. And then there are a bunch of offices within the office of the director, and that's where the office of dietary supplement is fixed. So I fall under the immediate office of the director in the division of Program coordination Planning and Strategic Initiatives. That's a now Eckes is what they call that. Okay. I don't know if this wasn't in front of me that I could actually say what the division is called without it being right in front of you. So Nila say they are working on a name change for that. The only problem was that is that it has to go through Congress for any kind of change for that. There are a number of offices within DPC. They all have the same job. Our job is to really coordinate science across the ICs, get the ICs engage in research, stimulate innovative research, pull people together, meaning resources and expertise, and identify what those critical needs are in science and put out the funding initiatives, manage large scale programs to really move things forward and make a change. We are one office within that program. What do we do? So the mission of the office of Dietary Supplements is the coordinated collaboration of innovative and cutting edge dietary supplement research across NIH ICOs centers and office office VNO A other federal agencies to foster knowledge and optimize health across the lifespan. We do that a variety of different ways. Our primary way by which we do that is we support research, use a variety of df fund Unlike an IC NDK or National Institutes of Aging. The DGs offices do not have direct funding authority. We use a variety of other mechanisms actually fund work. So if you were to submit a fund grant application for an RO one to NIDDK that had a dietary supplement component in it, and they score it very well and they were going to fund it. They would come to us and look to us to help co fund that grant over the life of the grant. That's how the DPGpzi offices help support science in the true funding of grants. That's one of one Other ways we do that is through contracts, government contracts, through interagency agreements, and also by coordinating large scale programatic efforts, where a lot of ICs should have been money to really go after a big effort together where you can get much more or bigger bang out of your buck when you have much more in the bank than you do with one DCC office alone. That's what we try to We also prioritize trying to advance the workforce. We have a number of different training opportunities for individuals interested in learning about dietary supplement science? We have a research practice that goes over a course of two days. I basically takes you from sim to nuts on how dietary supplement science actually occurs from all the way from product formulation, the analysis of that product, to running the studies, all the way out to the market in the trade organizations lobbying for dietary supplements. How does that whole piece work together? One of the most important parts of our office is communication, people take dietary supplements. Some of the estimates are on average in foster population around 58% of the population will use at least one dietary supplement. Of that, a significant amount is obviously multi vitamins and mineral supplements, but there's much more. As you increase in age and between sexes, those rates increase dramatically and individuals over 70 n and women report using about 70 or 80% of men and women report using dietary supplements. So nearly all older adults report using some form of dietary supplement, and the underlying reason that they take it is to improve their health. And our job is to understand whether or not it actually does that at all. So when I got there, I sat down in my boss's office. This is 2 hours after getting my ID. Sat down with his deputy director and he goes, we're so happy to have you here. We understand your last job. Put a lot on your plate. They asked you to make a lot of changes. Well, we know you can do it, and we want you to do it. I said, I just walked in the door. So what are you looking for? We want you to bring ODS package be fold and make it a powerhouse here at NIH. There is so much work. I'm going to show you in a subsequent slide. So much work being done in the area of dietary supplement. This is not enough coordination. We can do better if we work collaboratively, and that's one of the main things I've always did when I read my own. The first thing I had to do was develop a strategic plan. That was the bulk of my first year. That strategic plan is now online. It has about two more days left in public comments. If you go onto our website, there's a link for the strategic plan that's in draft form. Once we get all the comments back, that will be revised and it will be out published and it will be our active strategic plan by which we will operate for the next five years. Let me just give you a big picture overview of what we're trying to do here. I wanted our office to be fundamentally based on scientific priorities. We are a very small office with a medium budget. We can't be doing everything and we can't have N of one silos doing research. We need to come together as a group and identify what those priorities are and put our heads together and get some work done. Identify three broad categories and those are diverse population, healthy lifespan and resilience as our scientific priorities. Those priorities build upon the accomplishments of the office also emphasize our ability to pull in ICs who do research in these areas because they are broad enough. From there, I needed to build the foundation by which we operate. That really is the academic disciplines that we hold as strength within the office and the individuals that we collaborate as biological sciences, population sciences, and analytical sciences. And from there, I worked out from there, building the infrastructure. What infrastructure did we need to make our office actually function well. But we needed to advance methodology needed to apply all the skills we had, and we needed to reach out and branch out and figure out new ways to make the feel stronger, we needed to be really strategic on how we used our funds. We don't have money like National Master Institute. We really don't. We have a very small pocket of money, so we need to smart and strategic and how we invest that money. From there, we have our operations programs. Who keeps the office moving and running on a day to day basis? And that's all the programs on the outside. The key tenets to the strategic plan, I just want to call out are those highlighted, more trans IH, proactive versus reactive posture. Rather than wait for someone to come to the office with an idea for dietary supplement. I want to go out to the ICs and say, this is what I think is an emerging need that needs to be addressed. I have done that so far with several ICs, and we're starting to generate interest and some shared interests that I think are going to go forward into new initiatives. Regular reproducibility and transparency, that was one of the things I parked on during my interview process. Obviously, it's here in a strategic plan. The one thing that really I could never do if I was a leader is maintain status. Now, I'm not a manager. I know I have to manage and manage people. But my goal for the office is to provide vision, provide that big picture vision, provide those high level areas and motivate bide opportunities for my staff to go after those and be creative and curious to really address those the best if they can. I won't be keeping things as it is. That's really not my style. So going in there is about shaking things up a little bit, about really getting the office to the next level of prominence. So just a little bit more information about our cross spending priorities. For diverse populations, this is pretty straightforward. I understand the use of dietary supplements and their effects on health requires investigation into their use and impact in diverse population in the various intersection of these groups within the United States. Lifespan so should be pretty straightforward too to understand the association between dietary supplement use, disease prevention, and health optimization at different ages and life stages in the biological mechanisms through which dietary supplements impact health. And resilience, was kind of a budding area when I first got into the office. Vern Brown led a trans NA workshop to really define resilience for NIH, to define a research framework for resilience, resilience to the body's ability to respond to stress. So they led that initiative before I got on board. And when I got on board, I said, you know what Vern, I managed the portfolio on resilience in the EOD. I'm all for this. I understand that needs a heck of a lot of work for a DP, a more prominent area in the field. But a lot of people are using the term. I'm not sure if they use it all right, but a lot of people use the term. Let's do something and really make this intent. Resilience is one of our three pies. I want to quickly highlight a couple of emerging areas that we are going to act on. There are a good reason why we're doing that. Asesimated that about ten women will turn to dietary supplements to help offset the sichematology of going through medics. The efficacy of using those dietary supplements is unclear. Also how they use those dietary supplements, the exposure, the doses. We don't know very much about how dietary supplements are used in this population. We don't know how they're used across the disparate population in the US. You may be aware that a year ago, the president signed the Women's initiative Women's Health initiative, and that is being led out of the office of Research on Women's Health. We are working hand in hand with them to develop new scientific initiatives that look for non pharmacological treatments to help women at different life stages and menopauss being one of them. We are in the beginning stages of this. They just got their budget execution for FY 25, and we're working towards developing a workshop, and then the next steps will be what the funding requirements will be or funding announcements might be that come in. Now, one that's kind of near and dear to me, not because I'm a big GLP one receptor agonist person is because the misrepresentation of sinus. At ASN past year, American Sci nutrition Demos and chaired a session that was specifically on GLP one receptor agonist. It was amazing how many sessions at that meeting focused on this medication and focus on a variety of gals. I'm not interested in GLP one for its ability to improve insulin sensitivity or its ability to induce weight loss. I'm interested because the dietary supplement market is already decades past where the field is in terms of understanding how these drugs work in different populations. And this is a picture here from GNC. They already have all walls of dietary supplements that are meant. For GOP one. You're dealing with GOP one side effects, we got cure, and here they all are. They're just repurposed dietary supplements, I would assume that are just being said, well, this can help with nausea, this can help with constation, and got help. If you're losing muscle mac, we don't even know if that's legitimate at this point. But if you're losing muscle mass, here's some amino acid and protein supplementation take on top of that. What I want to do and where I see the gap is that the potential effects on nutritional status are one. If you have a poor diet to begin with and you're on this drug and it is changing dietary behavior, you don't want to eat. Change vegetables all day long, that nutritional status can be compromised. Access to healthy foods in that population could also be a issue. Couldn't change physical activity couldn't change b morphology, fracture risk, muscle quality in a population where musculoskeletal development is so important. I'm really looking more towards adolescent and young adults as a starting point to get moving. That's fit this figure here just shows a number of publications on GLP one receptor agonis as a whole. That's a dark line on top, that basically just says that there are a lot of dietie, a lot of studies on GP receptor agon. You look at the bottom of that point here. So if you look at the bottom of the graph, that is studies on just adolescents and children. I hasn't moved. So all of the studies that been on adults right now. And the reason why that's important is because the prescription rates on GOP one receptoragonous drugs in adolescents is sci. So this paper was recently published in JAMA in 2024, and they looked at prescription rates in individuals 17 and 18 to 25. They just looked at the prescription rates 2020-2023. Increase, dramatic increase in rates. Yet all the studies have been done on s. So we don't really have a lot of information, and likewise, we don't have a lot of information on any of these dietary supplements in this context. So I'm trying to generate some interest to see where this goes. I'm not looking to resurect the idea of weight loss supplements, but I want to know where this is a public health issue of concern. There are a lot of things that we don't understand about at this point from a nutritional standpoint. Just shifting gears, I'm going to talk about ODS and its mission to advance research integrity. We have three efforts to do that. One is the analytical methods of reference materials program or ARM. That's a program that's been around for about 22 years at this point. We have the NIH consortium for advancing research on mechanicals or other natural products or carbon. That really stepped from the NIH mechanical research centers back in 1999 and morphed over the last 25 years. Within our purview of reviewing grants, we also have a strong section on product integrity and we hold grants accountable to certain things. That's all summed up well in this figure here to the right, where the goal here all the way to the left, all the way to the right is you want to understand the phenotypical biological effect of the dietary supplement. If you work all the way backwards, you can't do that and you don't know what's in the dietary supplement. From a natural product standpoint, they spent we spent a lot of time trying to understand what are the constituents of that natural product? What are the active ingredients, where are the acbive ingredients, are they interfering with anything? What is actually accessible in the body? And then subsequently, I will available, would actually have an inaction on a various pathway in this case, g translation. So Those are all the steps by which we try to look at in the context of product integrity. Do we know that? Because if you're running a randomized trial and you have no idea something does, and at the end, you have an finding, what did you do? So that's an issue that has been a concern for the field for quite some time. We're working on that and we'll continue to do so. Just a little bit more information about ARM, it's focus on rigor and reproducibility. The goal of RMR is to provide materials, reference materials is a close collaboration with the National Institute of Standard and Technology in Gatsburg. And it works to coordinate and develop and disseminate resources that promote accurate and reliable chemical characterizations of dietary supplements, natural products or clinical biome. Just an example of some of the things that we produced, 56 newly available or reissue dietary supplement ingredient reference materials, and those are available on our website or available on this. They're also publicly available for I think Fisher, biaical, self. Ten newly available biomarker reference materials, and these have been referenced are cited quite a bit in the purview literature. There are people using our products. We also have other things available to researchers. And that is we have a data resource to facilitate dietary supplement characterization. Everything that we have done over the years is available on our website that a searchable that can provide people the right information to go and buy the materials they need to assess their dietary supplement accurately. A big win, I would say for AMA is vitamin D and standardization of vitamin D measure. The AAM program in the context of vitamin D developed the reference measurement procedures that are accepted by the Joint Committee on traceability and medicine for vitamin D metabolites and serum. They also developed the vitamin D binding protein, measurement and serum and developed the method for determination of vitamin D and 25 hydroxin D three in food and supplement agencies. So that kind spurred on the offices vitamin D initiative, and subsequently the vitamin D standardization program, which really came up with a consensus guidelines to standardize clinical measurements of vitamin D. And develop a methods for retrospective standardization of vitamin D status collected in clinical and population studies. This is a big deal that really helped to clean up the vitamin D data that was coming out probably 15 years ago when vitamin D was in craves. I would say the cure all for every issue you had with vitamD back in the 2010 period. So our work here really helped to standardize and make that matter. I'm not expecting anyone to read this, but what I wanted to show you here is that if you apply for a grain and it comes our way, we do have a lot of questions and answers available on our website about product integrity and what we would be looking you know, and this gets to the question, well, other ICs do the same thing when it comes to their grant applications. Do they describe this well enough research can make sure that they are addressing the appropriate things that we or the funding body wants to know are being done to make sure that the study is strong. I just want to show that here to give you one indication of what we are doing. But altogether, if you heard we say, all I've talked about is product integrity. That is one piece of the puzzle in terms of dietary supplement science. I have not talked about once experimental design, statistics and reporting. I challenge the staff when I got it and I go, let's look bigger. We'll continue to do Amandi that's important is making benefits. But let's expand our efforts to go to the complete picture of the experimental designs. Let's try to move away from a stetary supplement study of an N of five that's not randomized. Let's try to move away from that and make it more important and more impact. So I'm going to shift gears here to trust and dietary supplements sites. And this is the paper that just came out this came out last year. Health claims on doses of fish oil supplements in the United States I was published in Jama cardiology a brief report. The graph represents the variety of health claims. So they use our dietary supplement label database that we house. They looked at 20 100 or so fish oil supplements, and they found that 70% made at least one health claim. Those are all reflected in the bottom of this wrap. There's brain, joint, I, antioxid, cell membrane activity. The various categories that those health claims were nd 81% of those claims were structured function, meaning not on a clinical health outcome. 19% were actually able to use a MDA quality assured health claim. So only 19% of those actually met the criteria for an FDA claim. So that's significant. And then the doses that were used in these studies were all over the place. In some cases, the doses in the studies that had the labels that said that they met the criteria for a qualified health claim did not have the doses that actually would achieve that qualified health. So that's problematic. And I just on the right hand side, just show you what the actual qualified health claim for fish oil supplements are. And you can see even the FDA does not put out a conclusive statement. They're not saying that this is going to fix ADN C, but it is giving you something that's more than saying supports phone, protects muscle, that would be a structure function, a claim based on a mechanistic study. Then there's the impact of science flotation. I found this term to be pretty interesting. I find myself being someone who actually probably does it more than I should. It was coined by Timothy who's a lawyer, it describes how brands and markets borrow language from emerging areas of science to market improvement products. The buzzwords are like supports, boots promotes terms that are not quantifiable, but researchers media and marketing lead into these to really get vague health cleans out there and to stimulate people's interests to a product. There is an interesting paper in New story in the New York Times, how fake science sells wellness. It's true. You see here, research fact, medical grade, evidence fas. I can't tell you how many times that when I've done like an elevator pitch to a general that I say, Oh, what we're doing supports muscle. Well, that doesn't mean anything. But now I see that this is a thing that people when they just take buzzwords that we use just use without even thinking about it as scientists and those get pushed as having a meaningful health. A year ago before I started the office hosted doctor Marines. I don't know if any know she is, but she's very well known in the nutrition science field. And she gave a pretty provocative talk to the office. At one point she challenged the office. Her whole thing was about the politics of food science and the issues surrounding dietary subtle. And in her presentation and it's available on her website if anyone's interested to listen to it. She says, who's causing mistrust? She said, your office is contributed to mistrust in the field of dietary subtle where we sit back and say, well, I thought we were trying to do the opposite. Well, she says on your website, you'll have things that say everybody takes them, but not everybody needs them. Some have side effects, little evidence or benefit, need more studies, use precaution, FDA doesn't So I heard that and I said, well I'm not going to agree with everything she says, but I understand her point that the office who's trying to advocate for credibility is providing contradictory statements within the same document. So I think we need to do a better job of understanding how we message science around dietary supplements. So I just thought this was important to share. Like I said, I'm all for all of her points because it was a pretty pointed presentation that got a lot of feedback. But anyone wants to listen to it, it's available on. This table here was recreated from a recent manuscript published in 2021, and it talks about the limitations in nutrition science. Well, there are a lot of nutrition scientists in here who have clinical nutrition studies. There are many many, many, many problems or issues or limitations in terms of ni nutrition science. And I would say there are so many limitations across the board unless you're dealing with a potent drug trial as regulated by the FDA. So when we get into the nutrition context, I'll just poll out a couple of big ones. Complex nature of dietary trials to bear with conventional pharmaceutical trials. Okay. Relatively low incompatibility of dietary clinical trials with good clinical practice guidelines. Most people want to avoid that because it as an extra layer of regulation. For experimental design for adaptation with denational designs and put in trials, a slew of methodological problems and weaknesses. For reporting of trials in scientific literature, limited translatability of the observed effect, due to the effect size and the herogenita of the data, and high susceptibility to the founding variables. All of these limitations are there for every dietary supplement or dietary trial, including dietary supplement trials. More importantly, when you get into dietary supplements, there are more limitations that are above and beyond what's simply involved if you want to do a controlled feeding study, which I was saying much better than most. For example, we already talked about on the left hand side. You need to know it's actually in the dietary supplement. But once you know what's in the dietary supplement, doesn't mean that when it gets to be gut, it's actually dissolved and it disintegrates and it's bio accessible. There are studies that you can do and they are expensive, but they are disintegration and dissolution tests to understand of that capsule or that matrix, whatever that gummy, what is actually available and accessible to be bio available in tissue. Well, that those tests can be done. The problem is they're very expensive, they're labor intensive and not everybody has access to. But these are very important because you could very well have all the best intentions in mind. You know what your active ingredient is, but maybe only a tenth of it gets to where it needs to be. That's a problem. I think there's been some funny jokes or names about dietary supple that just sit in your gut. I can't really remember the needs, but Johanna Tier one of our consultants says this every time we talk about this issue she send just sits in your gut like a rot and doesn't do anything. I was like, Oh, That's that's what we're investing in, but I understand the point. These are just some of the steps that take. Then you understand actually have this modal available, the uptake and response in the cells, and then getting all the way over to maybe first rodent model and eventually a human. These are the steps. How many people bypass this and go right to here go right to animal or human trials, a lot of people. I'm not saying every study needs to start from the left all the way down to we'll get back to the left, but these things need to be considered to do a well controlled dietary supplement trial. You need to understand these variety of factors. The ter turn on that, anything is flooded with dietary supplement trials that are filled with limitations. We just pulled a couple of systematic reviews that were published this past year by one group. In one publication, they looked at 438 eligible studies, but they excluded 308 of those studies because of no randomization, no lack of relevant clinical outcome, short intervention periods, and the inclusion of participants with severe disorders which would have compounded. And they found very similar things when they looked at other micronutrient supplementation trials, and this are just another couple of references. The problem is that all of those studies, just because they didn't get involved in a meta or systematic review, they still exist. If you get these one offs, may not be the strongest study in the world, may have bias within the studies. They're still out there, they're still in the literature. People still refer to them and they attribute to the noise in the field, and they contribute to the confidence issue that we have in dietary supplements science. Well, this is not something new, it's been recognized from a lot of people that we have to do something to make nutrition science better, and with that comes dietary supplements. This is just a variety of recent review papers or perspective pieces that really talk about how can we make the field stronger? Well, papers are good. Fact, this paper here is Paul Coates, this is blue here. This paper here, I saw I say, look, even Paul is still thinking about this. People are thinking about ways to make nutrition science better and better reporting, better scientific design. But who is the one that can actually make a difference and try to do something about it? Well, considering we find the majority of dietary supplement sciences in the US, we should take the lead and try to do something to make you feel stronger. So should we or do we have an obligation? I I would question if we have an obligation. I'll tell you why. This is the funding layout for 2004 FI 22. Feral research funding and FI 22 is 32. Dietary supplement related funding was 241 million in FY 22, and that means anything related to dietary supplements. It doesn't have to mean take a supplement and measure this two months later. It could be mechoistic work or anything like that. Direct dietary supplement NIH funding nearly 71 million in FY 22. We contributed to 7.8 million that. In the grand scheme of things, there is a lot of money being spent on dietary supplement science, whether direct or indirect that is being funded by NIH. And could we be doing a better job of holding scientists accountable to integrity? And Rigor, we probably can. Now, this is just I'll provide the slide of David afterwards, in case you guys look at this. We ran a portfolio analysis. One of the tools that we have at NIH to really look at what's been done at NIH over the course of the years. So this portfolio analysis is a very quick and dirty analysis of FY 22. I asked doctor Kuzak, who's going to lead the Rigor program. Tell me whether or not all of these grants had information about rigor and reproducibility or product integrity in their grant. Well, on the right hand side, there are a variety of different statements that were included. Some of them just say they allude to a authentication of sources. They allude to source overall strategy and methodology. They don't give specificity at all. Some go into a great deal in terms of this probiotic study at yet. However, this is only a few rows of projects and this page eight, this one on multiple pages, and the majority of them were empty. There are a huge number of funding announcements without rigor in some form mentioned. There appears to be case by case driven by the IC, without any standard guidance. What can we do? Is NIH do this already? Well, they do. There is a great need for rigor reducibility of transparency that's well recognized at NIH. At the National Institutes of Neurological Disorders and Stroke, they have their Office of Research Quality, whose mission is exactly that to promote experimental analytical rigor, measures to reduce bias, transparent reporting, high quality scientific research. Well, they're working on it. There are efforts like this at NIH, that's a lot more than just NINDS. For example, the Office of Disease Prevention as the improved preventive research methods initiative. That's one of their key priorities that they make sure they focus on every year is evaluating the state of the science and looking for strengths and weaknesses and be able to provide up to dated information pertaining to prevention science and how to make it better. For example, they serve as a resource to ICOs on prevention science methods as they develop new funding opportunities, workshops meetings, and other activities. They collaborate with the ICOs and strengthen their policies and procedures to encourage applicants or investigator and shape awards to use the best available methods and application for prevention research. They review and conduct research methods, use in prevention research, using the portfolio analysis technique. This has made a real difference in the prevention side effect of prevention research at NIH. There are models that we can follow. When I got in there I said, well, we don't need to recreate the wheel, we need to learn from our colleagues at NIH, and we need to build a system in place that can actually do this at the office of dietary supplements. So that leads to our Rigor program and that's being led by doctor Adam usa who is currently leading the analytical methods of reference materials program. Adam was the perfect choice. I have never met a perhaps more detail oriented critical scientist than him I asked him for one thing. For example, I asked him for the portfolio analysis. Ten pages of funding announcements and all that little text. He's very good at doing this, and I think he's going to be a great me for this project. Let me give you a little idea of what this is going to be and where we're going to go. Well, the aim is to continue and grow our efforts to improve the rigor and translatability of dietary supplement science and related nutrition research. By really going after two main questions. Well, how can we as an office promote more comparable and reproducible evidence based on mechanistic and clinical research, and where should NIH resources and money for dietary supplement analytical sciences and our methodology capacity be prioritized? Those two questions really are the starting point for our conversation. The big picture goals. We want to expand our tools and collaborative efforts to promote progress in the rigor in which dietary supplement studies are conducted. Designed, evaluated for NIH funding consideration and reporting in literature. In my mind when I talk to Adam, east three are the most important. How studies are designed conducted, how they are evaluated and ultimately funded, and ultimately when they get to a journal, how are they reported? This is where I think we need to really focus. There's obviously a lot of details in between these. But if we can do this or even a portion of this, we will obtain a difference in. Initial steps, which Adam is doing right now, conducting NIH portfolio analysis, assessments of where NIH is addressing methodological challenges, supporting high priority research, and where more is needed. Etransion and development of resources, the age research, and experimental design, conduct, and assessment reporting and elevating dietary supplement research at NIH. The reason why I mentioned Elevate is because there are a lot of groups at NIH working elements. We need to have a set the table, and now because of Adam and because of this effort, we are now elevating dietary supplement to that conversation, so we'll learn from that. The anticipated products are just listed right here. Our goal is basically to try to make the field better provide guidance to funding announcements, provide guidance for researchers to help reporting on the back end overall, lead to more credible guides or supplements. So with that because of all that, I just want to thank you so much for your attention. If I can hear your questions, I'll answer them, but again, send and everybody who help this f happen. Thank you very much. I appreciate it. Okay. Happy question. Thank you. The wonderful presentation. Question have you got a huge incumbent lucrative business of lots and lots and lots of people selling lots of products through lots of channels, and as you indicated, very little rigorous science back in the mop. How do you handle the politics? How you in terms of moving through your vision of where it needs to be versus the starting state here. Can you talk about that and certainly doctor Senator Hatch from Utah, is meddling at all of this in terms of making your job infinitely more difficult. Yeah, the politics is different. As a DOD scientist, 20 miles out of Boston, you really didn't get into that. But it is present in this job. The biggest link is between our office of legislative policy Analysis and the trade organization. So there are a number of trade organizations that represent primary dietary supplement companies. Yeah, the Mom and pop things, I don't know what you're going to do about that. But they are the ones lobbying Congress for what needs to be done, where the emphasis should be. In my meetings with them so far, I said, My job is I'm going to come right down the middle. I'm not going into this with any bias. My goal is not to be gotcha. My goal is to be fair, will actually be a good sign. The relationship with them has been really great so far. They felt like the office and many have been in this gotcha. Look, we got you, it's bad. It's not doing anything. Now, what I said to them I go, I'm going to call out science when it says they do nothing. But if there's a study that says it works? I'm not going to be afraid to say that study worked. I'm always going to go, I don't know, it may work, it may not work. The politics is tricky because it comes from these big trade organizations and so far with Congress, the most that they have been influenced so far is the trade organizations some of them have been pushing for mandatory product listing with the FDA. We have almost the exact same thing. Now it's going to be the question of, does that actually get enacted into law? Will FDA establish this database, and what do we do with ours? There's some politics of that that will have to get a. S. It's fun. It's new it's different. They don't teach you that at school. Thank you. From an analytical assessment perspective, how far do you think you go? In the sense of there are organizations that publish official methods like USD, AAC, and in many cases, they'll have official methods for some of these bioactive substances. In your case, you deal with academic community a lot and my experience academic community doesn't necessarily care about those offical methods. My experiences are to try bios whatever excuses are too hard, charity practice, whatever. Would you think about actually recommending these approved methods and say here one, if you're going to work in this space, whether it's re clinical or clinical? Because to me that is foundational. It's number one, that one slide you have, you really need to know what your substance is, and how much of it you have. I mean, absolutely. I asked at dinner last night I was kind of giving them Some questions I gave myself when I first started and one of them was how you tell whether or not your program was having a benefit to return on investment. For that, any Methods program, I said, do we require people to use our methods? Do we have some criteria by which if they're asking for our funds and they're studying whatever Kirkman or something, that they're using a validated method that we know is valid or they're using something from AOEC or USP that we let know it's real versus just method developing in your own lab and trying to figure out We haven't yet, and I think that's a limitation. I do see as we move towards this, the guidance will be, if there is a validated measurement or reference material, you must use that because this way, we know that which studying is what's it going to be as opposed to shooting in the dark and hoping to got. And the follow up question. Then to the jury s. Yeah. Because often I would say when an article goes to a nutrition journal. The reviewers probably aren't focused on the analytical nature of it. So how do you get that translated from that first part to then the journal part where you have reviewers that know k. I'm looking at the analytical section, and you know, I I made this connection to OPS. And how they analyze this is it's like tier three for them. So we're going to start asking a lot of questions. Well, from the journal side, I think that's going to be the heaviest left of all of but there is There is evidence of some doing that. Connie Weaver led a group to try to amend the consort diagram for nutrition RCTs. That was published in Advances last January. I saw that. I was like, Well, maybe maybe we can do that. I a lot of the journals involved. Reviews are only as good as the actual reviewers. That's the limitation. So clear instructions. I don't know if everything will be an amendment to a consort. Maybe maybe you know how journals have expertise in statistics, maybe expertise in analytical chemistry for various journals. I don't know. That's way down the road, you know, in terms of the back end of the journals, but at least I know Connie and others are coming to give a seminar to the office early fall, talk about how they went about doing that for their effort to amend the consort diagram from nutrition studies because I think we have to do something similar. People need to you need to be you should be reporting exactly what you measured and that should be in the paper. If someone is someone remembered the whole thing about papers, you should be able to take that paper and redo the study and get the same thing. I don't know if that happens. So that's just we'll see what goes on that and I don't know I don't know what that will look like. Thank you. Great to. Thank you. Thank you Sha you mentioned FDA does not have regulatory someone they don't regulate, but you have forse au cross over into the drugs? They do regulate them in the context of foods. Right. Okay. But if you cross over into the drug space. Oh that Differ my question is does your agency have any collaboration you're seeing literature and see the trigger words. Do you have any enforcement requirements for the FPA partnership? Well we've worked closely with that group, but nothing in that sense. And a couple of words that stood out from your question. The word treat the sun from to play that actually is called out as prevent optimal but not treat a known disease. So that usually has prevented us from even playing in that space, but we'll see where things go. So I don't have a faith. I wouldn't say my goal is for the best evidence. I don't ever really design even, right? If that's what you observed or you observe it epideolgically, then, you made that claim, but Most of the times you're looking for a biological post. I don't I don't have one that I want to prove. I just want the science to be given. So I would be that amino acid. I'm like waiting for everybody to show me that amino acids ma you speak the strongest guy in the world. You know, I'm not looking whatever the evidence shows. So the office has being, I would say conservatively towards preventing harm, and you still promote that when there's reason to promote that. It's not there for everything. So if I need to make that message or say that message first think I will. But I don't have a I don't have one area of applicant. I really hope that let's kick ins. Station question was related to product integrity or authentication. So a pre clinical model rely on lab or collaboratory work with use of the chemistry. But if you're doing a trial, humans usually providing a supplement formula. So a third party authentication be recommended or would you recommend on compound interest like nitrate. You can do that. The issue is with a lot of supplements aren't good biomarkers that are reflective of the supplement doing anything. So there's an issue on that. Lack of biomarkers in nutrition in general isn't the greatest aspect of our field. If you're going to buy something off the market off the shelf, it says USP certified or something like that, When I have done that, I've always sent them out to I don't know what you call it used to be called CBNS. I would send them out to an external laboratory to analyze. I was always dealing with protein amino acids. I was a little bit easier than a natural product, but there are labs that do what I showed, which will I would work that into a budget, send a lie of what you have or several samples from a lot of supplements. I just one validation. For example, when I would publish on amino acids, I would say, this is what I wanted in it. This is what was analyzed, this is what they got, like a supplementary table or something. So I can at least report like exactly what within supplement. So I mean, if there are labs that can do it, I don't know off the top of my head, know all of them, but I could look into that. Hello. Thanks for tok. This thing cares a lot about transparency and about reproducibility. Where are we standing regarding the data availability stories? And what can we expect from pis in the next couple of years? I would say you can expect some calls for proposals that would go after reproducibility, taking existing data and trying to reproduce it. I you would expect something coming out to help us build the case for making things better. There aren't a lot of there's a growing body of I would say momentum at NIH now for Reproducing studies. Common fund, for example. They are now going to be forced to ask people to reproduce and replicate findings. So if you are funded by the C, I don't know if everyone knows what the common fund is, but big money studies, hundreds of millions of dollars studies and like motor paths people want to know if those are real. So now they're being asked by Congress to make sure there that you can repeat them. You get the same data. There is a bigger push for my office. That's a big scale. I can't afford that, but there are smaller things that we can do. Like some of the papers you worked on, I think that's a start, you know, in trying to understand what's been done and, you know, are things being done a report subpopulations ogenity in the patient, comorbidities and gender, et cetera. To what extent understanding the impacts, differential impacts in terms of different sub populations of these these actives that you're working with or supplements, any movement there or Yeah. Yeah. I was at a David was at the nutrition meeting in the fall. And one of the big things they talked about was diverse population, populations of health disparities, and I mean that's why it's one of our priorities. I want to understand how these supplements are acting within various groups. I want to understand if the heterogenic response is dictated by some demographic or phenotypic aspect that we don't know already. I think that could open the door for a lot of new research. I think there is a way to potentially apply, I would say, nutrition science. Truly understood AI feel if that was the case, starting to put the pieces together to understand you build like a phenotypic signature of how a population responds to a dietary su. That's exploratory work. I would love to see something. Thank you so much. So we have a beautiful and award for doctor Pasopos. And it's a glass award, and I will read the inscription. It says, This is a quotation. Almost every major systematic error which has deluded me for thousands of years, relied on practical experience, horoscopes, incantations, les, which The cures of medical practitioners before the advent of modern medicine, were all firmly established through the centuries by these methods. The scientific method in contrast was devised precisely for the purpose of elucidating the nature of things under more carefully controlled conditions and by more rigorous criteria. That is from Michael Pan personal knowledge. Then we have added. Thank you for lighting a candle in the darkness, promotion of rigor in nutrition science. You are following the tradition of Florence Florence Nightingale, who is known as the lady of the lamb, because she brought the lamb into the darkness, the date with a better nutrition.