Dr. Jeff Volek has been investigating how humans adapt to ketogenic—and carbohydrate-restricted diets for the past 30 years.  Today, Jeff returns to STEM-Talk to discuss a growing accumulation of studies supporting a ketogenic diet as a way to improve metabolic health, as well as research confirming the relative safety of dietary fat. Jeff is a professor in the Department of Human Sciences at Ohio State University. He is known for his research on the clinical application of ketogenic diets in the management of insulin resistance and type-2 diabetes. His research particularly aims to understand individual variability, including how well-formulated ketogenic diets alter fatty acid composition, lipoprotein metabolism, gut microbiome and overall metabolic health. Jeff has performed several prospective diet studies that demonstrate that well-formulated ketogenic diets result in substantial improvements in (if not complete reversal of) metabolic syndrome and type-2 diabetes. In today’s episode, we talk to Jeff about: — How a well-formulated ketogenic diet results not only in weight loss, but also leads to substantial improvements in insulin resistance as well as improvements in a number of cardio-metabolic biomarkers associated with metabolic syndrome. — The remarkable progress that has been made in the science of low-carbohydrate nutrition in the past 30 years. — How Jeff’s research has expanded to look at a well-formulated ketogenic diet’s potential in the treatment of mental health, heart disease and cancer. — An initiative Jeff is conducting to address how the poor metabolic health of the nation is impacting our military troops and therefore poses a significant threat to the future of the military and our nation’s defense. — We also ask Jeff about his thoughts on the recent popularity of fasting and time-restricted eating.  We then ask what his own daily dietary intake looks like. Show notes [00:02:48] Ken opens the interview welcoming Jeff back to STEM-Talk. Ken mentions that Jeff, who appeared on episode 43,  has perhaps published more research on the ketogenic diet and its effects on humans than anyone. While most STEM-Talk listeners are familiar with Jeff’s research, Ken points out that many people might not know that Jeff was once an accomplished powerlifter, achieving impressive numbers for his body weight. Ken asks Jeff what his best lifts were, and if his background in powerlifting inspired him to study exercise physiology. [00:05:25] Dawn mentions there is a paradigm shift in terms of low-carb diets and the public perception regarding the relative safety of dietary fat.  Americans have long been led to believe that saturated fats lead to obesity and heart disease. Dawn goes on to explain that in the last 20 years, there has been a steady accumulation of studies supporting carbohydrate restriction as well as the relative safety of dietary fat. Jeff addressed this in a paper in Science titled “Dietary Fat: From Foe to Friend?”, and also a paper in the Journal of the American College of Cardiology titled “Saturated Fats and Health: A Reassessment and Proposal for Food Based Recommendations” Dawn asks Jeff to talk about this research and what listeners should take from it. [00:08:37] Ken mentions that Jeff at one point in his life demonized fat, and was a strong advocate for low-fat diets. Ken asks what changed his mind on this issue. [00:10:04] Dawn mentions that when Jeff was interviewed back in 2017, he was in the early stages of launching Virta, a company that was founded in 2014 to address the type-2 diabetes epidemic that we’re seeing in the United States and across the world. Dawn asks Jeff to explain what type-2 diabetes is and how it’s different than type-1. [00:13:36] Ken explains that diabetes is a major cause of blindness, kidney failure, heart attacks, stroke and lower-limb amputation. In light of this, Ken asks Jeff if we know how many deaths can be annually attributed to diabetes. [00:14:54] Dawn explains that Virta’s website describes the company’s program as “blood sugar control without the drugs.” Virta works with diabetics to not only lower their blood sugar, but help them lose weight, eliminate their need for insulin and other medications, and restore their metabolic health. Dawn asks Jeff to give an overview of Virta and the progress being made in its endeavors. [00:17:57] Dawn mentions that Virta has had a number of recent papers and trials that have demonstrated some amazing results. With a paper in Nutrients last year that reported on the results of a two-year pilot study that highlighted the effectiveness and sustainability of Virta’s intervention in reversing a variety of metabolic conditions. Dawn goes on to explain that Virta was able to help 97 percent of its prediabetic patients in the two-year study to avoid type-2 diabetes. She asks Jeff, as the chief science officer of Virta, for his thoughts about the successful outcomes being seen by Virta’s trials and studies. [00:19:48] Ken shifts to talk about Jeff’s work at Ohio State. Jeff joined the university in 2014, and in the past decade has established the Volek Low-Carbohydrate Laboratory, which specializes in dietary carbohydrate restriction and nutritional ketosis. Ken asks Jeff to give an overview of the lab and the research that goes on there. [00:22:56] Dawn mentions that Jeff’s lab also has a team of registered dietitians who work with clients on a variety of approaches to low-carb and ketogenic diets. Dawn asks Jeff to talk about the services the lab provides. [00:24:59] Ken explains that a lot of people have the belief that a ketogenic diet is only about losing weight. Jeff, however, stresses that a well-formulated ketogenic diet results in not only weight loss, but also substantial improvements in insulin resistance and improvements on a number of cardio-metabolic biomarkers associated with metabolic syndrome. Ken asks Jeff to talk about the wide range of benefits people experience as a result of a ketogenic diet. [00:28:15] Dawn asks Jeff to talk about the symposium he and Ken as well as some other folks put together at Ohio State that addressed the remarkable progress that has been made in the science of low-carbohydrate nutrition. Jeff goes on to describe some the key takeaways from the symposium. [00:31:20] Dawn asks Jeff to talk about his lab’s research into cancer and how research has shown that the majority of tumors use glucose as their primary fuel source. [00:34:01] As a follow-up, Ken mentions the STEM-Talk interview with Colin Champ that centered on ketogenic cancer research. [00:34:17] Ken asks Jeff about a couple of pilot ketogenic diet cancer studies that are currently underway in his lab, as well as a pilot study that is specifically looking at advanced-stage breast cancer. [00:37:15] Dawn mentions that while weight loss is a common outcome of consuming a ketogenic diet, a question that has been rather controversial in the research community is whether there are metabolic improvements as a result of carbohydrate restriction that are independent of weight loss. Dawn explains that Jeff published a study last year in the Journal of Clinical Investigation Insight that found more than half of your obese study participants who were suffering from metabolic syndrome no longer met the criteria for metabolic syndrome at the end of a four-week low-carb diet, even though the participants didn’t lose any weight. The results demonstrate that irrespective of weight loss, a low-carb diet improves a host of metabolic problems. Dawn asks Jeff to talk about this study and the significance of its findings. [00:41:27] Ken mentions that Jeff’s lab is currently doing work with the military, going on to mention that Jeff’s lab received funding a few years ago to look into whether a ketogenic diet could help the military deal with its ongoing challenge of obesity among the troops.  The subsequent study showed that participants lost an average of 17 pounds after 12 weeks on the ketogenic diet, and as a group, the participants lost more than five percent of their body fat, and almost 44 percent of their visceral fat, and had a 48 percent improvement in their insulin sensitivity. Ken asks Jeff to go into further depth about this study and its findings. [00:46:07] Ken asks about Jeff’s project, currently underway, called “Strategies to Augment Ketosis,” or STAK. It’s a comprehensive initiative that is going to address the physical and financial toll attributed to the pervasive poor metabolic health of the nation and how this impacts our military troops, especially veterans, and therefore poses a significant threat to the future of the military and our national defense. Ken explains that there are multiple layers of research involved in STAK, many of which utilize ketone esters, and asks Jeff to explain what ketone esters are for those listeners who have not listened to episode 54 of STEM-Talk with Brianna Stubbs. [00:48:41] Dawn explains that one of the major topics being examined in STAK is sleep deprivation, which is a major problem in military populations, with only one in three U.S. Army Active-Duty Soldiers estimated to get their target of seven hours of sleep on duty days. Given that insufficient sleep leads to a drop in performance and an increase in errors, it is an important problem to solve. There is evidence that ketone ester supplements may lessen the adverse effects of sleep deprivation, and thus STAK will further explore this possibility. Jeff talks about the clinical trial he is putting together, which will look at whether ingesting a ketone ester supplement twice daily can improve cognitive and physical performance during short-term sleep restriction. [00:51:45] Ken follows up, asking Jeff what the rationale is for his hypothesis that ketosis will mitigate the negative effects of sleep deprivation. [00:53:48] Dawn explains that another element of STAK is exploring the effects of ketone esters and the sustained long-term effects of a ketogenic diet on type-2 diabetes and heart failure. Dawn asks Jeff to talk about this study, and why he thinks ketones would be beneficial for the heart. [01:00:28] Dawn asks about the STAK study looking at the possibility of delaying or preventing the progression of diabetic nephropathy. [01:02:24] Ken shifts to talk about work Jeff’s lab is doing on metabolic psychiatry. Ken goes on to explain that we have known for a long time that food choices can alter a person’s neurochemistry, but we are just now beginning to research the impact that macronutrients can have on our mental and emotional well-being. Jeff discusses this work and explains what metabolic psychiatry entails. [01:05:58] Dawn mentions that a common struggle for physicians who are strong proponents of a ketogenic diet is getting their patients to stick to it. Dawn goes on to mention our recent interview with Vyvyane Loh who talked about how some of her patients struggle with the diet and so she often ends up recommending a less stringent low-carb diet instead. Dawn asks Jeff his thoughts on this, as well as the critique of the ketogenic diet that it is not sustainable. [01:12:03] Dawn talks about the so-called keto flu being a hurdle that many people feel they can’t overcome, and asks Jeff what his thoughts and advice are about this. [01:16:08] Ken mentions the current popularity of fasting and time-restricted eating. Going on to say that while fasting is an effective way to get into ketosis, Jeff has reservations about fasting, particularly those that last beyond 24 hours. [01:20:36] Dawn mentions the surge in new products on grocery shelves advertised as keto breads, keto donuts, keto bagels, etc. Dawn asks Jeff what his thoughts about the flood of keto-branded products we’re seeing. [01:25:56] Dawn describes Jeff as a walking testimonial for ketogenic and low-carb diets. Jeff has followed a low-carb diet for more than 20 years, all the while maintaining a healthy body weight and lipid profile. Dawn asks Jeff to share with listeners what his daily dietary intake looks like and how the diet benefits him. [01:29:07] Dawn closes the interview by asking Jeff where he sees the field of ketogenic research going in the next decade, and if the dietary recommendations might change in that time. Dawn goes on to mention that Jeff published a recent article with several prominent co-authors titled          

Our guest today is Dr. Ed Weiler, a retired NASA scientist who spent 20 years as the chief scientist for the Hubble Space Telescope, the forerunner of the James Webb. During his 33-year NASA career, Ed wore many hats, including Associate Administrator of the Science Mission Directorate; Center Director of NASA’s Goddard Space Flight Center, Associate Administrator for NASA’s Space Science Enterprise, chief of the Ultraviolet/Visible and Gravitational Astrophysics Division and director of the Astronomical Search for Origins Program. In today’s episode, we talk to Ed about: — NASA’s accomplishments in the past year, including the Perseverance mission, the success of the James Webb telescope, and the launch of Artemis-1. — Ed’s experience as the Chief Scientist for the Hubble Space Telescope during its early development. — Ed’s time as the director of NASA’s Astronomical Search for Origins program. — Ed’s role in the development of the New Horizons space craft and its mission to fly by and study Pluto and it’s moons. — Ed’s belief that in the next 20 to 50 years, we will be able to the prove the existence of other life in the universe. Show notes [00:02:59] Dawn opens the interview mentioning that she and Ed share a common experience of going through the selection process to become a NASA astronaut. [00:03:55] Dawn mentions that instead of becoming an astronaut, Ed joined NASA in 1978 as a scientist, serving in a variety of science leadership roles throughout his career, eventually retiring in 2011 after 33 years of service. Dawn asks Ed to talk about his various accomplishments at NASA. [00:05:57] Dawn asks Ed about his feelings toward the various accomplishments of NASA in recent years since his retirement, such as the Perseverance mission, the success of the James Webb telescope, and the launch of Artemis-1. [00:08:42] Ken asks Ed to discuss the recent images from the James Webb telescope, images that have captured the public’s imagination. [00:12:10] Dawn asks if it’s true that Ed decided to become an astronomer and go to work for NASA when he was only 13 years old. [00:15:36] Dawn mentions that we have had several guests on STEM-Talk that cite the Apollo missions as their inspiration for pursuing a career in science. Dawn points out that Ed was already in grad school when Neil Armstrong first stepped on the moon. Dawn asks Ed about watching the moon landing on the campus of Northwestern University. [00:16:48] Ken asks about Ed’s experience as the Chief Scientist for the Hubble Space Telescope during its early development. [00:25:01] Dawn points out that after graduating from Northwestern University, Ed joined the research staff at Princeton while also working at the Goddard Space Flight Center. In 1978, Ed became a staff scientist at NASA headquarters and Dawn asks how that position came about. [00:29:45] Dawn mentions that Ed was also the director of NASA’s Astronomical Search for Origins program and asks Ed to talk about that experience. [00:33:03] Ken mentions that in 1998, Ed became the Associate Administrator for Space Science for the first time. Ken goes on to mention when Ed was first approached about the position, he said “not in a million years.” Ken asks what eventually changed Ed’s mind. [00:37:10] Dawn asks Ed about his first stint as NASA’s Associate Administrator, where he oversaw several successful missions and set in motion an ambitious Mars exploration mission. [00:43:43] Dawn asks Ed to talk about the role he played in the development of the New Horizons craft and its mission to fly by and study Pluto and its moons. [00:45:46] Ken mentions that when Ed’s first tenure as Associate Administrator for the Science Mission Directorate ended in 2004, he took over the leadership of the Goddard Space Flight Center, which is one of the premier institutions for space and earth science missions. Ken asks Ed to talk about the work he did at the center. [00:50:06] Dawn mentions that Mike Griffin, our guest on STEM-Talk episodes 23 and 134, was the NASA Administrator in 2008, and asked Ed to return as Associate Administrator. Dawn asks why Ed was brought back again and what he was asked to accomplish. [00:56:47] Ken asks Ed about one of his priorities at NASA, which was RTGs (Radio-Isotope Thermo-Electric Generators).  Ken asks Ed why this was a priority, and what that experience was like. [01:00:21] Dawn mentions that Ed was an early proponent of STEM education, and during his time as Associate Administrator at NASA, he required all project proposals to set aside one to three percent of their budget for STEM education. Dawn goes on to ask Ed about a letter he received from a Mexico City student in the early days of Hubble that made an impression on him. [01:06:38] Dawn mentions that Ed has been quoted as saying that in the next 20 to 50 years, we will be able to prove the existence of other life in the universe. She asks Ed why he’s so confident about that. [01:14:13] Ken follows up on the previous question and asks Ed what his thoughts are on the Pentagon’s recent report on Unidentified Aerial Phenomena (UAP), which Ken and Dawn discussed in episode 127 of STEM-Talk. While the study does not imply that these UAPs are extraterrestrial crafts, the report does indicate that they are likely physical objects of some kind.  Ken asks Ed what he thinks these objects are? [01:20:32] Dawn wraps up the interview by mentioning that Ed has been known throughout his career for building effective teams and, toward that end, he would often take his staff water skiing. Ed Weiler Wikipedia page Learn more about IHMC STEM-Talk homepage Ken Ford bio Ken Ford Wikipedia page Dawn Kernagis bio    

Today’s interview is with IHMC’s Dr. Gwen Bryan, a research scientist who investigates wearable robotic devices aimed at augmenting human performance in clinical, occupational, and military applications. She is particularly focused on maximizing the benefits of powered exoskeletons. At IHMC, Gwen leads the exoskeleton team, which is developing a novel augmentative device that continues IHMC’s research on mobility devices for people with spinal cord injury. The team also is researching a powered exoskeleton to aid government employees whose work involves nuclear site remediation. Gwen and her team’s effort, which utilizes a human-centered research approach, is uniquely situated to expand exoskeleton research and technology because of the expertise and collaboration that’s available among IHMC’s robotics and human-performance research groups. Gwen joined IHMC after completing her Ph.D. in the Stanford Biomechatronics Lab. Outside of work, Gwen enjoys soccer, weightlifting, painting and snowboarding. She also is a dog mom to two very adorable shelter dogs, Bandit and Oreo. Show notes: [00:02:32] Dawn asks Gwen what it was like growing up in Albuquerque, New Mexico. [00:03:02] Dawn mentions that it seems science was a part of Gwen’s life early on. Dawn goes on to mention that Gwen’s father was an engineer, and her mother was a nurse and asks how her parents having these backgrounds influenced her. [00:03:35] In addition to a science background, Gwen’s mother is also a clarinetist who instilled a love for the arts in Gwen.  Dawn asks Gwen about her painting and how art benefits other aspects of her life. [00:04:17] Ken asks Gwen what she was like as a kid. [00:04:59] Ken asks Gwen to talk about a rafting trip she took with her cousin through the Grand Canyon. [00:06:27] Dawn asks Gwen how chocolate chip cookies factored into her third-grade science fair project. [00:08:04] Dawn mentions that fitness became a part of Gwen’s life following an injury she had as a senior in high school. Exercise, particularly weightlifting, helped alleviate her back pain. Dawn asks Gwen what her fitness journey taught her about her body, and ultimately, how that experience gave her insights into the work she does today. [00:09:16] Ken asks Gwen how she chose to go to the University of Texas in Austin. [00:10:38] Dawn mentions that Gwen transferred to the University of New Mexico for her undergraduate work. Dawn asks Gwen what motivated her to apply her interest in mechanical engineering into robotics. [00:11:28] Ken asks Gwen what was involved in her transfer from the University of Texas to New Mexico. [00:12:34] Ken asks Gwen what led her to the Stanford Biomechatronics Lab. [00:13:38] Ken asks Gwen to talk about her internship with the Sandia National Research Labs. [00:14:40] Dawn shifts to talk about Gwen’s current research focus on wearable robotics, particularly exoskeletons, mentioning that when the public hears this term most people generally think either insect exoskeletons or Ironman. Dawn asks Gwen to describe the exoskeletons she works on. [00:15:25] Dawn mentions that the potential uses of exoskeletons to help people with limited or no lower-limb mobility seems, in some respects, clear, but the application has been limited, and asks why that is. [00:16:40] Dawn asks what some other applications of exoskeletons are that are important to know about. [00:18:35] Ken mentions that during Gwen’s doctoral work at Stanford, she developed the first cable-driven exoskeleton to assist all the three leg joints — hips, knees, and ankles — and asks Gwen to talk about how that design was developed and what made it special in the exoskeleton field. [00:20:10] Ken explains that Gwen’s work also developed novel control systems for exoskeletons by using feedback from real-time physiological measurements of the user – coined human-in-the-loop optimization (HILO). Ken asks Gwen to talk about this strategy, and why it is an important innovation. [00:21:56] Ken asks Gwen to talk about what she learned about the impact of exoskeleton assistance on walking economy when assisting the hips, knees, or ankles individually versus simultaneously. [00:22:58] Dawn asks if the multi-joint strategy depends on the walking task, mentioning that it seems as though demands change for different joints when walking faster; or up and downhill; or carrying load. [00:23:49] Dawn explains that the laboratory emulator approach seems to have led to many fundamental findings. Dawn goes on to ask, however, about the limitations of assisting people in the real world in an approach that has users stuck on a treadmill and in the lab. [00:25:02] Dawn asks if exoskeletons are a ‘one-size fits all’ technology, or if they need to be customized to each individual. [00:26:08] Ken mentions that Gwen is involved in a couple of exoskeleton projects at IHMC, and asks first about the Eva project. [00:28:16] Dawn asks what other applications Eva, or exoskeletons in the same vein, might have in rehabilitative or therapeutic settings. [00:29:01] Dawn asks about IHMC’s Quix, another exoskeleton that Gwen is working on, which has been primarily used to help people with lower-body paralysis gain movement. Dawn goes on to mention that the team has been looking into rehabilitative applications that Quix could serve in as well, and asks Gwen to discuss new developments with this project. [00:31:27] Ken asks Gwen to share some final thoughts on exoskeleton and what she sees as the grand challenges facing exoskeleton development. [00:33:18] Dawn asks about Gwen’s passion for cultivating interest in STEM among girls and young women and why that is so important to her. [00:34:59] Gwen talks about some of the mentors in the field that helped her along the way. [00:36:11] Dawn asks Gwen about her two rescue dogs, Bandit and Oreo, to close the interview. Links: Gwen Bryan bio Learn more about IHMC STEM-Talk homepage Ken Ford bio Ken Ford Wikipedia page Dawn Kernagis bio

Our guest today is Dr. Dan Pardi, the CEO of humanOS.me, a digital health training application. Dan is well-known for his research into sleep and has collaborated with many high-performing organizations, from Silicon Valley venture capitalists to companies like Adobe, Salesforce, Workday, Pandora, Intuitive Surgical, and more. He also works with several branches of the U.S. Military to help elite warfighters maintain vigilant performance in both combat and non-combat conditions. Dan’s podcast, humanOS Radio, is the official podcast of the Sleep Research Society, the Canadian Sleep Society, and a content partner of the Buck Institute on Aging. Dan collaborated with more than 100 science professors around the globe to create his digital humanOS application. Dan has a Ph.D. in cognitive neuroscience from Leiden University in the Netherlands and Stanford University in the United States. He has a master’s degree in exercise physiology from Florida State University and currently lives in Austin, Texas, with his wife, two young boys, and their dog, Wally. Joining STEM-Talk host Dr. Ken Ford for today’s conversation with Dan is Dr. Marcas Bamman, a senior research scientist here at IHMC. Marcas was a STEM-Talk guest on episode 116. In today’s interview with Dan, we cover his early career in bioinformatics and how a trip to Moscow led to his doctoral research of sleep and treatments for narcolepsy. He also talks about the Loop Model to Adopt and Sustain Health Behaviors, a program he developed during his Ph.D. studies. The Loop Model became the core of his company, humanOS. Finally, Dan talks about the concepts of “actual health,” health-performance experts and a shift in what aging means, which he believes is important to improving the quality of life for all of us. Show notes: [00:03:19] Marcas starts the interview by asking Dan to talk about his years growing up in Northern California’s Marin County. [00:04:06] Ken asks Dan about building radio-controlled cars with his father. [00:05:11] Marcas explains that Dan’s father was a successful businessman who, after a successful career as a salesman for Remco selling kitchenware, started his own company in California that grew to 200 employees. Dan has been quoted as saying that one of the lessons he learned from his father was the value of relationships. Marcas asks how that lesson has affected Dan’s life. [00:06:29] Dan talks about his passion for basketball and how his time at the Cap Lavin camp influenced his early life. [00:08:15] Marcas mentions that Dan’s “science life” seems to have begun with a seventh-grade science-fair project that ended up landing him a job with Nike. Marcas asks Dan to talk about that story. [00:09:26] Ken mentions that Dan went to the University of San Francisco for his bachelor’s degree and then went to Florida State for his Masters in Exercise Physiology. Ken asks what led Dan to FSU. [00:10:26] Ken asks why Dan decided to pursue a career in cancer research, going to work at the Preventive Medicine Research Institute in Northern California after graduating. [00:12:04] Marcas commends Dan for being ahead of his time by leveraging the new technological development of the internet portal to empower life scientists while he was working with the Bioinformatics Biotech DoubleTwist, and asks what that experience was like. [00:13:41] Ken asks Dan how a trip to Moscow led Dan to pursue a Ph.D. at Leiden University and Stanford, after already working in the industry for 10 years. [00:15:17] Marcas explains that Dan’s Ph.D. research at the Zeitzer Circadian Biology Lab at Stanford University focused on gamma-hydroxybutyrate (GHB), sleep and ingestive behavior. Marcas asks what was most interesting about this research for Dan. [00:16:24] Marcas asks about a randomized controlled trial that Dan conducted to look into ecologically relevant amounts of sleep loss. This trial enrolled 50 participants and manipulated their next-day alertness by randomly assigning different levels of sleep. Dan talks about the findings of this study. [00:21:50] Marcas explains that while Dan was working on his Ph.D., he developed a behavior model called the Loop Model to Adopt and Sustain Health Behaviors. Marcas goes on to explain that Dan has presented this model at several healthcare conferences, such as Stanford Medicine X and Health 2.0, and asks Dan to explain what this model is and how it works. [00:24:53] Marcas mentions that Dan’s company, humanOS.me, is described as a digital health training application and asks what this means. [00:26:23] Ken mentions that simply giving people more information doesn’t drive changes in health-related behaviors, and asks how humanOS.me approaches things differently to address this problem. [00:29:03] Ken asks if Dan sees any downsides in tracking health markers. Ken mentions that STEM-Talk listeners often ask about the quality of data collected, but Ken goes on to say that there are also problems of becoming hyper-focused on things like sleep and food to the point where these things are no longer pleasurable experiences at all. [00:35:02] Ken asks about the concept of health, mentioning that in 1948 the World Health Organization defined “health” as “a state of complete physical, mental and social well-being and not merely the absence of disease or infirmity.” Ken mentions that this definition has been criticized for being too demanding and asks Dan what his thoughts are on this definition. [00:37:51] Marcas mentions that a biogerontologist named Suresh Rattan at Aarhus University in Denmark, defines health as the maintenance of homodynamic space, and asks Dan to explain for listeners what this means. [00:42:44] Marcas asks Dan what he means by “Actual Health,” the concept that is the core of the upcoming book that Dan is co-authoring with STEM-Talk guest Josh Turknett. [00:44:56] Marcas mentions that Dan has been working on developing the concept of a health performance expert, and to set the stage for this discussion, Marcas asks what Dan’s views are on the gaps in our current healthcare system and how these might be addressed. [00:50:17] Ken mentions that he likes that Dan’s idea of a health performance expert is something that should develop independently, even in coordination with, the current sick-care system. Dan elaborates on this idea. [00:57:47] Marcas explains that in Dan’s TED talk on optimizing light for health, he opened by talking about the impact of microgravity on health. Marcas asks Dan to talk about why he chose to open with that topic. [0:59:47] Ken shifts to talk about the difference between age and aging, making the point that we often think of aging as a continual decline from our peak but goes on to say that age and aging are more nuanced than that infers. [01:07:20] Marcas mentions that from an evolutionary biology perspective, age and experience are valuable to the success of one’s progeny and the tribe one’s offspring inhabit, as the grandparent hypothesis posits. Marcas asks if Dan agrees that this emphasizes the importance of working at preserving our cognitive functioning as we age. [01:10:27] Marcas asks Dan to talk about his personal practices to maintain or improve overall health, and what the key ingredients of optimized health are. [01:16:36] Marcas asks Dan what he hopes will be the key takeaway for people to remember from this episode. Links: humanOS Dan Pardi bio and IHMC lecture Learn more about IHMC STEM-Talk homepage Ken Ford bio Ken Ford Wikipedia page         Should this not be a link to Marcas?

It’s time for another Ask Me Anything episode where STEM-Talk cohost Dawn Kernagis asks Ken questions submitted by listeners. In this episode, Ken and Dawn weigh in on: —  Whether AI is becoming sentient. — How women in midlife might protect their bodies from the negative effects of a slowing metabolism. — A Stanford study that compared a low-carbohydrate diet with a Mediterranean diet. — Whether fasting helps optimize cognitive performance. — The future of hypersonic technology. — And a lot more. If you have a question after listening to today’s episode or any episode of STEM-Talk, email your question to STEM-Talk Producer Randy Hammer at rhammer@ihmc.org. Show notes [00:02:45] Dawn begins the AMA with a question for Ken that was inspired by the Mark Mattson interview, episode 133. Mark talked about skipping breakfast and in his recent book,  “The Intermittent Fasting Revolution,” Mark points out that bodybuilders often skip breakfast and do their weight training in a fasted state, which has the effect of optimizing both muscle building and cognitive performance. The listener mentions that they feel more cognitively sharp in a fasted state but as soon as they break their fast, they don’t feel as sharp. The listener asks Ken if this is normal. [00:04:35] A listener asks Ken about a recent news story in which a Russian robot broke a boy’s finger during a chess match. The listener goes on to state that several of their friends have jumped to the conclusion that this is proof robots are becoming sentient beings and asks Ken for his take is on this given Ken’s AI background. [00:06:02] A listener asks another AI question, this one regarding the Washington Post’s reporting on a Google engineer who was fired over claims he made while at the company that an AI chatbot he had been testing had become sentient. The engineer claimed in an interview with The Guardian that the chatbot, LaMDA, was afraid of being turned off, had read “Les Miserables” and that it had emotions. Google maintains that LaMDA is merely responding to prompts designed for it. The listener asks Ken what would be an appropriate test for gauging AI sentience and what other thoughts Ken has about this story. [00:08:32] A listener mentions that they have been following the ketogenic diet for 18 months and have lost 40 pounds. Recently they checked their liver enzymes GGT, AST, TSH and found they were elevated above “normal” and their Alpha fetoprotein marker was measured at 10.3. The listener asks Ken what he has learned about the ketogenic diet’s impact on the liver. [00:09:48] A listener asks about a recent paper regarding a Stanford study that compared low-carbohydrate diets with a Mediterranean diet. The listener mentions that in the Stanford study the diets had three similarities – no non-starchy vegetables, no added sugars and no refined grains. The key difference in the diets was that the low-carb diet avoided legumes, fruits, and whole grains while the Mediterranean diet included them. The study measured glucose control and cardiometabolic risk in people with prediabetes and type 2 diabetes. The study found that comparative outcomes did not support a sufficient benefit to justify people avoiding legumes, whole fruits, and whole grains to achieve the metabolic state of ketosis. The listener asks Ken for his thoughts on the study and in his answer, Ken mentions an interview Dr. Ben Scher did with one of the study’s authors, Dr. Lucia Aronica. [00:14:57] A listener mentions in their question that they found the Mike Griffin and Mark Lewis interviews both fascinating and worrying. The listener’s key concern is that China and Russia are ahead of the U.S. in terms of hypersonic capabilities. The listener goes on to mention that they recently saw “Top Gun Maverick” and asks if it is reasonable that someday we will see jets with human pilots that are capable of flying 10-to-20 times the speed of sound, as depicted in the film; or will these sorts of aircrafts need to be operated by AI or humanoids. [00:18:17] A listener sends a question that reads, “They say that 50 is the new 30, but after listening to STEM-Talk, I now know that I can expect my metabolism to fall off the “50-cliff” once I meet the chronological milestone of turning 50 years old.”  The listener says it’s her understanding that hormonal changes related to midlife, especially for women, are key drivers of metabolic changes that lead to everything from brain fog to weight gain. The listener would like to know what she and other women can do to ward off the negative effects of aging and a slowing metabolism. [00:19:53] A listener mentions that in the Satchin Panda interview, Dr. Panda says that black coffee in the morning probably won’t break an overnight fast, but that coffee with cream will. The listener goes on to say that they listened to a Dave Asprey podcast in which he said drinking “Bulletproof Coffee” with two tablespoons of butter and two tablespoons of brain octane fuel was okay in the morning because it will elevate a person’s blood ketones to 0.7 millimoles per liter within 30 minutes. The listener asks Ken for his thoughts on this advice. [00:22:33] Dawn closes the AMA with a listener question asking if Dr. Ford has any particular pet peeves that he is willing to share. Links: Learn more about IHMC STEM-Talk homepage Ken Ford bio Ken Ford Wikipedia page Dawn Kernagis bio

Our guest today is Dr. Jason Fung, a Toronto-based nephrologist, and the best-selling author of “The Obesity Code,” “The Diabetes Code,” and “The Cancer Code.” Jason is best known for his success in combining a low-carb diet with intermittent fasting to help thousands of overweight patients reverse their type 2 diabetes, lose weight, and improve their metabolic health. Jason is the author of the blog “The Fasting Method” and the co-founder of the Intensive Dietary Management program, an initiative that provides low-carb dietary guidance and counseling on various fasting regimes. Jason is also the co-author with Jimmy Moore of “The Complete Guide to Fasting,” which looks at the history and culture of fasting and how it helps people improve their metabolic health. In today’s episode, Ken is joined by Visiting IHMC research scientist Dr. Tommy Wood and together, they and Jason discuss: How in the beginning of his practice, Jason prescribed insulin for type 2 diabetes patients. How a series of landmark studies starting in 2008 changed Jason’s mind about using glucose-lowering medication for type 2 diabetes. Jason’s realization that type 2 diabetes is largely a dietary disease and therefore requires a dietary solution rather than a pharmaceutical one. The origins of Jason’s Dietary Management program, which counsels overweight and obese patients to follow a low-carbohydrate, high-fat diet to reduce insulin. A critique of the “eat less, move more” strategy acclaimed by many obesity experts. Mark Mattson’s research into the powerful impact of intermittent fasting on metabolic health and a recent paper that questioned the effectiveness of time-restricted eating when compared to daily calorie restriction. Recent research and evidence that fasting during chemotherapy may reduce the side effects of the treatment. Show notes: [00:02:25] Tommy opens the interview mentioning that Jason was born and raised in Toronto and asks what drew Jason to science as a kid. [00:03:43] Tommy mentions the irony that Jason has written several best-selling books, yet Jason was not fond of English or writing when he was in school. [00:04:53] Ken mentions that after graduating from high school, Jason stayed close to home and attended the University of Toronto, entering into medical school just after turning 19 to study internal medicine, eventually specializing in nephrology. Ken asks Jason what intrigued him about becoming a kidney specialist. [00:06:36] Tommy asks Jason what led him to go to UCLA after medical school for his specialty training in kidney disease at Cedars-Sinai Medical Center. [00:07:37] Tommy mentions that Jason has been practicing clinical nephrology in Toronto since 2001, and that in those early years of his practice, Jason saw patients with type 2 diabetes and prescribed medications to keep their blood glucose low. When that didn’t work, he would prescribe insulin, which is the standard medical practice. Tommy asks what Jason observed during these early years of his practice. [00:09:28] Ken mentions that in 2008, two landmark studies were published, the ACCORD study and the ADVANCE study (a summary of ADVANCE). These studies were followed by two more studies, the ORIGIN and VADT studies, all four of which demonstrated that using blood glucose-lowering medication for type 2 diabetes didn’t necessarily have the expected benefits. Ken asks Jason to talk about how these studies were eye-opening for him and confirmed his own experience in treating patients. [00:16:27] Tommy explains that in 1972 Robert Atkins published the “Dr. Atkins’ Diet Revolution,” which shared his findings on the effectiveness of low-carb, high-fat dieting. Tommy goes on to mention that in the late 1990s, a string of Atkins-styled diet books surged in popularity, with most physicians being opposed due to the conventional wisdom that these high-fat diets would cause heart disease. As a result, several trials were launched in the early 2000s to prove this point. Tommy asks Jason to talk about how these trials revealed that the real story is more nuanced than people might think. [00:20:42] Ken mentions that even though Jason and countless other doctors were appalled at the notion that high-fat diets were being promoted as safe and effective, Jason and other physicians had virtually no nutritional training during their years in medical school. Ken asks if, in hindsight, Jason believes this is something that needs to change. [00:24:49] Tommy explains that Jason’s realization that type 2 diabetes was largely a dietary disease and therefore required a dietary solution rather than a pharmaceutical one led him, along with Megan Ramos, a medical researcher, to establish the intensive Dietary Management program in Scarborough, Ontario, in 2011. The object of this program is to counsel overweight and obese patients to follow a low-carbohydrate, high-fat diet to reduce insulin. Tommy asks about the results of this initiative. [00:28:56] Tommy points out that when when Jason started seeing positive results with his patients losing weight and getting off their medications with a high fat diet, Jason started giving lectures around Toronto. He  eventually posted a six-part lecture on the etiology of obesity on YouTube and starting a blog, “Intensive Dietary Management,” which evolved into “The Fasting Method.” This all received good feedback and opened the door for Jason to write a book, “The Obesity Code.” [00:30:43] Ken explains that Jason’s book begins with a critique of the “eat less, move more” strategy acclaimed by many obesity experts.  Jason points out in the book that while this sounds like a reasonable approach to weight loss, the approach has generally been ineffecitve. Ken asks Jason to elaborate on this. [00:37:08] Tommy explains that there is substantial experimental evidence that the “eat less, move more” approach is not particularly effective advice for individuals in an environment that promotes being sedentary while surrounded by hyperpalatable, calorie-dense, low-protein food. Tommy goes on to say that this does not imply that an integrated calorie balance model is incorrect, only ineffective. Tommy asks Jason for his thoughts. [00:46:58] Ken mentions that in Mark Mattson’s appearance on STEM-Talk, he talked about his recently published book, “The Intermittent Fasting Revolution: The Science of Optimizing Health and Enhancing Performance.” Ken goes on to say that in this interview Mark talked about a paper he had in the New England Journal of Medicine that highlighted how studies in animals and humans have shown that eating in a six-hour window and fasting for 18 hours has been shown to have positive effects on lifespan and a wide range of chronic disorders including obesity, diabetes, cardiovascular disease, cancers, and neurodegenerative brain diseases. However, a recent paper that appeared in the same journal reported that a year-long study among patients with obesity found that a regimen of time-restricted eating was not anymore beneficial – with regard to reduction in body weight, body fat, or metabolic risk factors – than daily calorie restriction. Ken asks Jason for his opinion on this recent study. [00:55:54] Ken mentions that Jason’s answer has circled back to efficaciousness versus effectiveness, and asks if Jason would agree that fasting is a more effective method than calorie restriction to lose weight because it is easier to follow. [00:57:52] Tommy asks if Jason agrees that calorie restriction is efficacious but not effective because it is hard for people to follow. [00:58:45] Tommy asks Jason about his third book in what has been referred to as the wellness series, “The Cancer Code.” [01:02:35] Ken explains that there is obviously a genetic aspect to cancer, but our environment also plays a huge role in the development of cancer. Jason points out in his book that a Japanese woman who moves from Japan to San Francisco often doubles and or triples her risk of cancer. Ken asks what makes the environment of the U.S. such a risk factor, and what makes the environment in Japan protective. [01:05:47] Ken mentions that there is also evidence that fasting during chemotherapy may reduce the side effects of the treatment. Ken asks Jason to talk about this and how fasting might also increase the efficacy of chemotherapy. [01:07:50] Tommy mentions that he understands that Jason weighs the same as he did in high school, and asks what his diet and fasting protocol look like. [01:11:15] To wrap up the interview, Ken  asks Jason for his take on rapamycin and concerns about the risk-reward ratio of using rapamycin as a prescription medication. Links: Learn more about IHMC STEM-Talk homepage Ken Ford bio Ken Ford Wikipedia page Tommy Wood IHMC bio Tommy Wood University of Washington bio Jason Fung  bio  

Today’s episode features the author of “Why We Get Sick,” Dr. Ben Bikman, a biomedical scientist at Brigham Young University. Ben is known for his research into the contrasting roles of insulin and ketones as key drivers of metabolic function. In “Why We Get Sick,” Ben takes a deep dive into insulin resistance and metabolic health. The book particularly focuses on the role that insulin resistance plays in many of today’s most common diseases: heart disease, diabetes, cancer, and Alzheimer’s. Ben and his colleagues at the Bikman Lab investigate the molecular mechanisms behind the increased risks of disease that accompany obesity and excess visceral fat. Much of the research at the Bikman Lab particularly focuses on the etiology of insulin resistance and how it disrupts mitochondrial function. In today’s interview, STEM-Talk cohosts Drs. Ken Ford and Dawn Kernagis talk to Ben about: How insulin resistance is tied to multiple chronic diseases. The relevance of ketones in mitochondrial function. How so many of our modern chronic diseases are self-inflicted and driven by insulin resistance. How many of the hallmarks of aging are a consequence of insulin resistance. The theory that the longest-lived people are likely the most insulin sensitive. The benefits that occur with carbohydrate reduction as a result of increasing insulin sensitivity. Ben’s thoughts about the degree of intermittent fasting needed to induce autophagy in humans. Show notes: [00:02:32] Dawn begins the interview asking Ben about his early life growing up in a small farm town in southern Alberta, Canada, as one of 13 children. [00:02:48] Dawn asks Ben what he was like as a kid and what made him stand out from his 12 brothers and sisters. [00:06:01] Dawn asks about Ben’s mother’s influence and how she wanted her sons to be Renaissance men. [00:08:29] Ken asks about Ben’s experience as a Church of Jesus Christ of Latter-Day Saints Missionary in Samara, Russia. [00:15:18] Dawn mentions that while Ben went into his undergrad majoring in exercise science, he wasn’t that interested in science at the time. It wasn’t until he began working on his master’s degree at BYU with Dr. Will Winder that he developed a true interest in science. [00:19:49] Dawn asks Ben how he ended up at East Carolina University for his Ph.D. in bioenergetics. [00:21:42] Ken mentions that Ben, after completing his Ph.D. moved to Singapore for his postdoc work at the Duke National University of Singapore. Ken asks how that came about. [00:25:49] Dawn mentions that Ben is well-known for his work on insulin resistance, stemming from his time at East Carolina when he realized that insulin resistance is tied to many different chronic diseases. Dawn asks what was Ben’s ah-ha moment that led him to focus his research on insulin resistance. [00:27:49] Dawn mentions that much of Ben’s work is focused on the role of elevated insulin in regulating obesity and diabetes, as well as the relevance of ketones in mitochondrial function. Dawn asks if it is correct that Ben has been on a sort of mission as a professor to teach a new generation of doctors and nurses how insulin resistance works, and why it is so relevant in terms of chronic disease. [00:29:56] Ken mentions that Ben began to take his message about insulin resistance beyond the classroom, appearing on podcasts and making YouTube videos, and also giving a speech to the student body at BYU, titled “The Plagues of Prosperity” making the case that the human race is currently eating itself into metabolic disarray. [00:32:31] Ben’s book “Why We Get Sick” points out that historicall, people got sic because of infectious diseases. In modern times, due to sanitation, vaccines, and antivirals, that is less of an issue. Today more people are afflicted by chronic illnesses, many of which are related to metabolism. Dawn explains that the overarching message of the book is that these diseases are, in part, self-inflicted, and partially driven by insulin resistance and hyperinsulinemia. Dawn goes on to say that while it is fairly well-known that insulin resistance plays a role in cancer, heart disease, and diabetes, many people may not know that it also contributes to neurological disorders, reproductive health, kidney disease, gastrointestinal disorders, and even reduced muscle mass, bone loss, and even hearing loss. [00:34:42] Ken explains that Ben has often pointed out that many of the hallmarks of aging are partially a consequence of insulin resistance. Ben has also pointed out in his book the theory that the longest-lived people are likely the most insulin sensitive. Ken asks Ben to elaborate on this. [00:41:36] Ken mentions that in Ben’s book, he explains that there are three primary causes of insulin resistance, the most obvious one being chronically elevated insulin levels. In addition to this, however, the second category is stress hormones including cortisol and epinephrine. The third cause is inflammation. Ken asks Ben to elaborate on these three causes. [00:45:15] Dawn asks Ben to talk about why our healthcare system has a glucose-centric view of metabolic health. [00:50:26] Ken points out that there’s a lack of consensus on what optimal levels of insulin should be. He also points out that most Americans do not have optimal levels of insulin since most are metabolically unhealthy. Ken asks Ben for his thoughts on what a person’s optimal level of insulin should be. [00:53:34] Ken brings up the problem with the reliance on “normal” readings since unhealthy people skew the average and therefore what is considered normal. Ken asks Ben to talk about how this leads to people who are ketogenic being flagged by their physicians because their insulin levels are low according to their charts. [00:59:25] Dawn asks Ben why he believes building and using muscle is a key component in the fight against insulin resistance. [01:01:03] Dawn mentions that Ben advises people to control carbohydrates, prioritize protein, and “fill with fat.” Dawn asks about the numerous benefits seen with carbohydrate reduction via increasing insulin sensitivity and lowering hyperinsulinemia. [01:03:55] Ken asks Ben to give a quick primer on the process of autophagy, with respect to intermittent fasting. [01:07:54] Ken mentions that a lot of the research about autophagy and fasting uses rodent models.  Autophagy is activated much more quickly and to a much greater extent in rodents than in humans. In light of that, Ken asks Ben if we know to what degree intermittent fasting induces autophagy in humans and how long a fast would have to be to incur that effect. [01:11:01] Ken asks Ben to explain how the standard American diet drives fat storage in the body and slows a person’s metabolic rate. [01:16:53] Dawn brings up that recent studies have shown that ketones are not only viable fuel sources for all cells with mitochondria but are also legitimate signaling molecules that elicit advantageous changes in inflammation, cognition, oxidative stress, and more. Additionally, ketones may be relevant metabolic fuel in the context of physical activity and athletic performance. Dawn mentions that further exploration of this can be found in episode 94 of STEM-Talk with John Newman on the topic of beta-hydroxybutyrate, or BHB, and episode 54 with Briana Stubbs on the topic of ketones and athletic performance. Dawn goes on to mention that in a paper published by Ben in 2018, in a special issue of the International Journal of Molecular Science, Ben wrote about the effects of ketones on metabolic function. He reported on the results of a study that sought to shed light on the specific effects of the ketone body BHB on muscle cell mitochondrial physiology. Dawn asks Ben to walk listeners through the results of this study and its implications. [01:20:54] Ken mentions that looking at the role of ketones on the maintenance of muscle, it appears that ketones have less of an anabolic role and more of an anti-catabolic role, which produces a strong protective effect against sarcopenia. Ben talks about this. [01:23:02] Ken mentions that we could make a serious dent in our obesity and type-2 diabetes epidemics if people would think more seriously about insulin and if more physicians tested for it. Ken asks Ben what research, in this regard, are he and his colleagues excited for on the near-term horizon. [01:27:03] Dawn shifts topics to ask Ben what his exercise routine looks like. [01:30:29] Dawn closes the interview by asking Ben if he still plays any instruments. Links: Ben Bikman bio Ben Bikman Lab Learn more about IHMC STEM-Talk homepage Ken Ford bio Ken Ford Wikipedia page Dawn Kernagis bio  

Our interview today is with Dr. Vyvyane Loh, a board-certified physician in obesity and internal medicine. She is the founder and leader of Transform Alliance for Health, a Boston preventive-care practice that  specializes in weight management and the treatment of chronic metabolic diseases such as diabetes, hypertension and dyslipidemia. She and her staff are known for helping people lose 50 pounds or more and getting their type-2 diabetic patients off their many medications. Vyvyane has spent her medical career developing expertise in immunology, metabolic syndrome, fat metabolism, clinical nutrition, and preventive medicine. In today’s interview, we discuss how abdominal, or visceral, fat is linked to a wide range of metabolic disorders. Vyvyane goes on to explain how there’s a clearcut association between obesity and decreased brain volume that rarely gets discussed. When her overweight patients complain about their behavior around food and how they consistently give in to snacks that patients know are bad for them, Vyvyane explains how the challenges they are facing is often a result of the brain struggling with decreased blood flow and the shrinkage of neurons. Vyvyane also shares how a patient asked Vyvyane if she knew anything about the Atkins diet, and although she didn’t, Vyvyane ended up doing the diet along with her patient. This led Vyvyane to start seriously researching whether a ketogenic diet could help people not only lose weight, but also reverse chronic disease. Toward the end of today’s interview, we explore Vyvyane’s interest in macrophages, which are specialized cells involved in the detection and destruction of bacteria and other harmful organisms. We also have a nice discussion about how Vyvyane took some time off from practicing medicine to enroll in the writing program at Warren Wilson College in North Carolina in 1999. She spent the next two years writing a novel, “Breaking the Tongue.”  Set in Singapore during World War II, her book was nominated for the prestigious International IMPAC Award in fiction and was selected by the New York Public Library as one of its top 25 books of 2004. If you are interested in finding out more about Vyvyane, check out her website, vyvyanelohmd.com. Also, Vyvyane launched a podcast this week, which you also can find on her website. Episode one looks at “Metabolism: What It Is, And How It Affects Your Health.” If you enjoy today’s interview with Vyvyane and the many other interviews we’ve had on STEM-Talk discussing the treatment and prevention of chronic metabolic diseases, you may want to check out the upcoming virtual conference on Targeting Metabesity. Our cohost Dr. Ken Ford will be one of nearly 70 speakers, including many former guests on STEM-Talk, talking about the growing evidence that the major chronic diseases of the day share common metabolic roots and as a result may also share common solutions. To find out more about the conference, follow this link to the Targeting Metabestiy home page where you find a program guide and list of speakers. If you would like a free ticket to the conference, click on this link where you will find instructions on how to receive a code for complimentary admission that is being offered to STEM-Talk listeners. Ken will be moderating a session on emerging research related to endogenous and exogenous ketosis in health and disease as well as the role of ketones in mild traumatic brain injury and the prevention and treatment of cancer. If you have enjoyed the interviews we’ve had on STEM-Talk with Drs Steven Austad, Colin Champ, James Kirkland, John Newman, Brianna Stubbs, Jeff Volek and Morley Stone, who are all speaking at the conference as well, you should find the talks by the over 70 speakers quite interesting and beneficial. So, click here to request a free registration and we will make sure to send a you a code for a complimentary ticket. Show notes [00:04:45] Dawn mentions that, based on the interviews she’s listened to with Vyvyane, that writing and dance have been passions of hers since she was a child. Dawn then asks Vyvyane at what point did she become interested in science. [00:05:25] Dawn asks Vyvyane how she ended up in the states attending Boston University. [00:06:25] Ken asks why Vyvyane decided to double major in biology and classics. [00:08:14] Ken mentions that Vyvyane’s classics advisor has a connection to the town of Seaside, near where IHMC is located. [00:09:01] Dawn shifts topics to talk about Vyvyane’s research, and asks about TOFI, which stands for “Thin Outside, Fat Inside.” It refers to people who outwardly appear thin, but have a disproportionate amount of adipose tissue in their abdomen, as well as “normal weight obesity.” [00:10:58] Ken mentions that the TOFI phenomenon helps to highlight the relative lack of utility of BMI, which is just a function of the relationship between a person’s height and weight, meaning that people with TOFI will look fine in terms of BMI, and someone who is lean and muscular may be categorized as obese by BMI, particularly if they are not very tall. Ken asks Vyvyane to elaborate on this. [00:12:26] Dawn explains that abdominal, or visceral, fat is of particular concern because it’s a key player in a variety of health problems, more so than subcutaneous fat. She goes on to explain that visceral fat is found deep within the abdominal cavity, where it pads the spaces between our organs. Dawn asks Vyvyane to talk about how visceral fat is linked to a wide range of metabolic disorders. [00:14:37] Ken explains that obesity often causes endothelial dysfunction, which results in the vasculature being inflamed and damaged, resulting often in decreased blood flow to the brain. Ken asks Vyvyane to talk about her frustration with the fact that this clearcut association between obesity and decreased brain volume rarely gets discussed. [00:17:22] Dawn mentions that it is estimated that just 12 percent of Americans are categorized as metabolically healthy. She goes on to mention that researchers at the University of North Carolina published a study that found that just one in eight American adults have optimal metabolic health. [00:18:22] Ken asks Vyvyane what she has learned about metabolic disease in her practice that she didn’t learn in medical school or her residency. [00:19:10] Dawn asks about the prevalence of using food to relieve stress in the wake of the COVID-19 pandemic, and what effects of this trend Vyvyane has seen in her practice. [00:20:13] Ken asks about Vyvyane’s practice, which she started in 2015 because she had been working in the medical system and came to the realization that she couldn’t develop a new way of providing preventive care from within the system. [00:21:53] Dawn mentions that Vyvyane’s practice is called the Transform Alliance for Health, and the website is quoted as saying: “Chronic stress and emotional issues commonly lead to using food to self-medicate or self-soothe. The visible result, the patient’s weight, becomes the focal issue for their healthcare providers. For us, however, it is merely the physical manifestation of the patient’s internal struggle with his/her real problem. From this starting point, we work with our patients to uncover their deeper and often more complex reasons for overeating and to take charge of their lives.” Vyvyane elaborates on this approach to her practice. [00:23:29] Dawn mentions that she listened to an interview with Vyvyane where she talked about how a ketogenic diet can often reduce inflammation and reverse metabolic disease, but that it can be hard to get people to stick to a ketogenic diet. Dawn asks if this is why Vyvyane emphasizes going on a low carb diet for her patients rather than a strict ketogenic diet. [00:25:07] Ken asks about the struggles of having to convince patients to give up carbs. [00:27:17] Dawn explains that non-alcoholic fatty liver disease is today one of the most common maladies in the United States, with a remarkable 30 to 40 percent of adults in this country having it. Dawn asks Vyvyane to discuss NAFLD and what she sees as its causes and the most efficacious treatments. [00:29:07] Dawn asks about the markers Vyvyane uses in evaluating a patient’s metabolic health, including insulin resistance scores and advanced lipid panels. [00:31:45] Ken asks about the curriculums Vyvyane offers for her patients, which explain to them the importance of sleep and mobility and strength training as a way of pressing the body’s “the reset button.” [00:34:00] Dawn mentions that we recently had Greg Potter and Jeff Iliff on the podcast to talk about the importance of sleep and particularly how a lack of sleep can lead to many negative health outcomes. Dawn goes on to mention that something Vyvyane has emphasized in the past is the role of nocturnal blood pressure dipping during sleep. Dawn asks Vyvyane to explain what she means by that, and how a lack of it increases a person’s risk for silent strokes and kidney dysfunction. [00:35:45] Ken asks Vyvyane to talk about her recommendations for protein intake as it relates to body composition and sarcopenia. [00:39:18] Ken asks Vyvyane to talk about some of the immune cells that are involved in regulating metabolic health. [00:41:34] Dawn mentions Vyvyane’s recent lecture at IHMC, titled “On the Magical Mystery Macrophage Tour, where she refers to macrophages as mysterious, specialized cells of innate immunity that play significant roles in some of our most common medical conditions ranging from cardiovascular disease to gastrointestinal disorders to obesity to osteoarthritis. Vyvyane elaborates on what these cells are and their various functions. [00:43:02] Ken asks how and when Vyvyane first became interested in macrophages. [00:43:41] Ken mentions that macrophages also stand out because they possess the unique ability to become polarized in response to different environmental stimuli and asks Vyvyane to explain how this works. [00:46:22] Dawn explains that macrophages can detect products of bacteria and other microorganisms using a system of recognition receptors such as toll-like receptors or TLRs. Vyvyane explains the role and significance of these receptors. [00:48:13] Dawn mentions that tissue-resident macrophages, or TRMs, are heterogeneous populations originating either from monocytes or embryonic progenitors and distribute in lymphoid and non-lymphoid tissues. Dawn asks Vyvyane to talk about the diverse roles that TRMs play in many physiological processes, including metabolic function. [00:50:46] Ken mentions that current medical practice still looks at obesity through the lens of caloric balance. Ken asks what new discoveries in obesity research challenge that dogma. [00:54:39] Dawn asks about the aspects of Vyvyane’s life outside of her medical practice such as writing, dance, and choreography. [00:55:47] Ken mentions that Vyvyane’s novel, “Breaking the Tongue,” was selected as one of the Top 25 Books of 2004 by the New York Public Library and in 2006 was nominated for an International IMPAC Award, which is the world’s richest prize for a single work of fiction published in English. Ken explains that the novel chronicles the fall of Singapore to the Japanese in World War II, and asks Vyvyane to talk about the book and how it deals with issues of race and class. [00:58:08] Ken mentions that Vyvyane has another novel she is working on, but that it, and her fiction writing as a whole, is on hold because she is working on a nonfiction book. Ken asks Vyvyane to talk about this new book. [00:59:47] Dawn closes the interview asking about Vyvyane’s morning routine, which incorporates an hour of meditation. Dawn also asks what else Vyvyane does on a regular basis. Links: Vyvyane Loh bio Vyvyane Loh podcast Learn more about IHMC STEM-Talk homepage Ken Ford bio Ken Ford Wikipedia page Dawn Kernagis bio    

Our guest today is Dr. Jeffery Iliff, a professor of psychiatry and behavioral sciences in the Department of Neurology at the University of Washington. Much of Jeff’s research focuses on neurodegeneration and traumatic brain injury. He is the associate director of research at the VA Puget Sound Health Care System and a co-leader for research at the University of Washington’s Alzheimer’s Disease Research Center. In this episode, we talk about Jeff’s investigations into the glymphatic system, which is a newly discovered brain-wide network of perivascular spaces that facilitates the clearance of waste products from the brain during sleep. Jeff goes on to describe how he is exploring how the glymphatic system fails in the aging brain as well as in younger brains after traumatic brain injury. Jeff and Dawn also have a conversation about their collaboration on a research project  that’s focused on how extreme stressors impact the glymphatic system. Together they are investigating a potential approach to optimizing glymphatic clearance for individuals with acute or chronic sleep deprivation. Show notes: [00:02:55] Dawn opens the interview asking Jeff where he grew up. [00:03:21] Dawn asks what Jeff what he was like as a kid. [00:04:01] Ken mentions that it wasn’t until Jeff was working as a lifeguard at a boy scout camp that he first became interested in science. Ken asks Jeff what it was about his lifeguard experience that triggered the interest. [00:05:06] Dawn asks what led Jeff to the University of Washington as an undergrad. [00:06:02] Ken mentions that Jeff originally intended on going into pre-med. Ken explains that Jeff changed his mind and asks about a suggestion from a girlfriend that caused Jeff to have a change of heart. [00:07:39] Dawn points out that in addition to working in the lab as an undergrad, Jeff also worked a 48-hour shift as an EMT over the weekends. Dawn asks Jeff why he kept such a busy schedule. [00:09:35] Ken asks what led Jeff to the Oregon Health & Science University for his Ph.D. [00:10:53] Dawn asks if it’s true that Jeff’s wife played a big role in his decision to travel across the country to New York for his post-doc at the University of Rochester. [00:13:06] Dawn mentions that after the second year of Jeff’s post-doc, he was promoted to a junior faculty position because he was part of the team that discovered a brain cleaning system known as the glymphatic system. The team published a paper in 2012 in science translational medicine that was the first of about ten papers that later became known as the “glymphatic papers.” After a follow-up paper in 2013, Science Magazine cited the discovery that the glymphatic system cleans the brain during sleep as one of the “Top 10 Breakthroughs of 2013.” Dawn asks what this experience was like for Jeff as a young post-doc and junior faculty member. [00:15:55] Dawn explains that the lymphatic system is a network of vessels extending throughout most of the body that transport excess fluid and waste from the interstitial spaces between cells to the blood. She goes on to explain that these vessels are notably not found in the brain leading to the question of how interstitial fluid is cleared in the brain. Jeff’s team discovered the glymphatic system, which serves the same function in the brain as the lymphatic system in the rest of the body. This discovery turned out to be a paradigm shift and led to numerous subsequent studies. Dawn asks Jeff how the initial 2012 study came about and how they identified a distinct clearing system in the brain that serves a lymphatic function. [00:19:59] Dawn mentions that after Jeff’s initial work in the glymphatic system, he went on to write what has become known as his sleep paper. Dawn goes on to say that for this study, Jeff used two-photon microscopy to visualize fluid moving in and out of the brain, and at some point, saw his tracer leaving the brain. Dawn asks Jeff what this experience was like. [00:23:55] Ken asks Jeff to explain the relationship between sleep cycles and the glymphatic system. [00:26:33] Jeff explains some of the differences in sleep between mice and humans. [00:28:35] Ken asks if the critical role of slow-wave sleep in glymphatic function and clearance explains the potential relationship between sleep deprivation and increased risk of neurodegenerative disease. [00:31:29] Ken asks about the impact of sleep deprivation of normal cognitive function. [00:32:43] Ken asks if there is any research on the glymphatic function of APOE4 carriers. [00:35:33] Ken asks about work done by Jeff’s postdoc mentor, Maiken Nedergaard, that suggests that glymphatic function can even be impacted by sleep that is outside the normal circadian rhythm, potentially explaining the increased risk of neurodegenerative disease in shift workers. [00:38:50] Dawn mentions that Jeff’s 2013 sleep paper became the predecessor for many subsequent neuro-imaging studies looking at glymphatic function in the human brain, leading to the pursuit of new neuro-imaging techniques for the measurement of glymphatic function and asks about the developments in this area. [00:42:36] Ken asks about Jeff’s 2014 paper in the Annals of Neurology, in which he proposed that impaired glymphatic clearance contributes to cognitive decline among the elderly and may represent a novel therapeutic target for the treatment of neurodegenerative diseases associated with the accumulation of misfolded protein aggregates. [00:46:44] Ken asks if there is thought to be a connection between glymphatic function and other disorders like Parkinson’s, vascular dementia, etc. [00:48:45] Dawn asks about the meningeal lymphatic system, which consists of lymphatic vessels running parallel to the dural venous sinuses and middle meningeal arteries, and how it relates to the glymphatic system. [00:52:01] Ken asks Jeff why he thinks the glymphatic system had not been identified until recently. [00:54:48] Ken asks about Jeff’s move from the University of Rochester back to Oregon, and how Phil Knight, founder of Nike, played a role in this decision. [00:56:14] Dawn mentions that Jeff was at Oregon for six years, but during this time became connected with a research group at the VA Puget Sound Health Care System in Seattle, which is an affiliate of the University of Washington. Dawn asks what led Jeff to return to Washington, where he currently works as a professor in the Department of Neurology and is the Associate Director for Research at the VA Center, as well as what he and his research group are currently studying. [01:00:24] Ken asks how traumatic brain injury (TBI) affects the glymphatic system. [01:02:44] Dawn mentions that in TBI, Aquaporin-4, or AQP4, is a water channel expressed in astrocytes throughout the central nervous system as well as in epithelial cells in various peripheral organs. The expression of this protein changes in the setting of TBI. She goes on to explain that AQP4 is involved in brain water balance, neuroexcitation, astrocyte migration, and neuroinflammation and is the target of pathogenic autoantibodies in neuromyelitis. Jeff’s 2017 paper in JAMA Neurology looked at how altered AQP4 was associated with aging brains. Dawn asks about this paper, and the implications that the loss of perivascular AQP4 localization may be a factor that renders the aging brain vulnerable to the misaggregation of proteins in neurodegenerative conditions such as Alzheimer’s. [01:05:30] Dawn mentions how the collaboration between her and Jeff’s teams involves working on several studies involving human glymphatic imaging in different settings. Dawn asks Jeff to explain the efforts in validating a non-invasive contrast-free imaging approach to visualizing glymphatic function in humans. [01:08:30] Ken asks Jeff to explain why validating new imaging approaches against intrathecal contrast MRI is so important for the clinical and research communities. [01:12:06] Dawn explains that the first study she and Jeff officially started working on together is funded by the Office of Naval Research, and kicked off in 2021. In this study, they are assessing the impact of extreme environmental conditions on glymphatic function in humans, ranging from hypoxia, hypercapnia, and hyperoxia. Dawn asks Jeff to talk about the status of these studies and their impact on future human glymphatic research. [01:16:28] Dawn asks about a paper Jeff and his team published on astronaut brains post-flight and whether fluid-filled spaces in the brain, known as perivascular spaces, are enlarged post-flight. [01:19:41] Dawn mentions that one of the biggest questions she gets about the glymphatic system is if it can it be ‘fixed’ to function better if it has been impaired. Dawn asks Jeff how he would answer this question based on the current state of research. [01:21:46] Dawn asks Jeff if there are any nutritional or exercise approaches that might help improve glymphatic function. [01:22:53] Ken asks if Heart Rate Variability (HRV) plays a role in glymphatic function. [01:24:52] Dawn mentions that her and Jeff’s collaboration has expanded to include Dr. Miranda Lim at Oregon Health and Science University, Dr. Don Tucker at the Brain Electrophysiology Lab, and Dr. Jeffrey Heys at Montana State University. They are working on DoD funded study to look into a device that could potentially stimulate the glymphatic system in individuals who are acutely or chronically sleep deprived. [02:27:10] Ken asks what should the next key studies in glymphatic research focus on. [01:29:29] Dawn asks if Jeff still takes time off from his lab work to go watch his son’s baseball games and his daughter’s softball games. [01:30:22] Ken asks if it’s true that Jeff is a huge fantasy football fan, and that when he was a post-doc fellow, he and some colleagues started a fantasy football league that is still going on all these years later. [01:32:15] Dawn says she assumes Jeff is a Seattle Seahawks fan and asks Jeff if he ever had Russel Wilson on his fantasy football team. [01:33:15] Ken asks if it is true that Jeff’s students are fans of STEM-Talk. [01:34:19] Dawn closes the interview telling Jeff to let his students know to write a review of this episode so they can get a free STEM-Talk t-shirt.

Today we would like to introduce you to one of our newest colleagues here at IHMC,  Dr. Kaleen Lavin, a research scientist who investigates the molecular mechanisms by which the body adapts and reacts to stressors such as exercise, training and aging. Kaleen came onboard at IHMC last year and is known for her use of computational biology techniques as a means to understand and improve human health, performance and resilience. She also is interested in the use of exercise as a countermeasure for a range of disease conditions, including neurodegenerative diseases such as Parkinson’s disease. Today we will talk to her about some of her most recent work that examined the molecular effects of exercise training in skeletal muscle and in people with Parkinson’s. We also talk to Kaleen about her recent paper that took a comprehensive look at the current literature surrounding the molecular and cellular processes underlying the molecular benefits that exercise induces in humans. The paper appeared earlier this year in Comprehensive Physiology and was titled, “State of Knowledge on Molecular Adaptations to Exercise in Humans.” Kaleen is a graduate of Georgetown University, where she earned a bachelor’s degree in biology. She also earned a master’s in sports nutrition and exercise science from Marywood University in Pennsylvania and a Ph.D. in human bioenergetics from  Ball State University in Indiana. Show notes: [00:03:02] Dawn opens the interview mentioning that Kaleen grew up in Scranton, Pennsylvania, and asks Kaleen about her passion for music as a youth. [00:03:25] Ken asks Kaleen about her high school years and how she became  a competitive swimmer. [00:04:26] Dawn mentions that Kaleen was an excellent student growing up, but that it wasn’t until her junior year of high school that she became interested in science. Dawn asks if it were a teacher who inspired Kaleen. [00:05:21] Dawn asks what led Kaleen to attend Georgetown University after graduating from high school. [00:05:57] Dawn asks if Kaleen knew she wanted to major in biology when she first arrived on campus at Georgetown. [00:06:45] Ken asks about Kaleen’s experience of becoming a part of the Howard Hughes Program at Georgetown, which led to her gaining experience working in lab. [00:08:47] Dawn mentions that Kaleen transitioned from competitive swimming to running during her undergraduate years, running a marathon and half marathon. Dawn asks if  Kaleen’s father, who is an avid marathoner, gave her the incentive to start signing up for marathons. [00:13:19] Dawn asks Kaleen about a faculty advisor who noticed her passion for running and exercise and helped her decide what to pursue for her master’s degree. [00:15:23] Ken asks Kaleen what led her to pursue her master’s at Marywood University, a small Catholic University in Scranton. [00:16:56] Ken asks Kaleen what prompted her to pursue a Ph.D. in exercise science at Ball State University, which has one of the longest-standing human performance programs in the country. [00:17:57] Dawn mentions Kaleen’s experience with no-breath laps as part of her training when she was in high school on the swim team. Dawn asks Kaleen to explain what no-breath laps are. [00:19:00] Dawn asks Kaleen about a study she conducted for her master’s thesis at Marywood that examined the effects of controlled frequency breath swimming on pulmonary function. [00:22:13] Ken asks about how Kaleen’s time at Ball State set her up for her post-doc work at Center for Exercise Medicine at the University of Alabama at Birmingham. [00:24:31] Ken asks what it was about UAB that attracted Kaleen to do her post-doc work there. [00:26:08] Dawn asks about a study published in 2017 by a group at UAB led by Marcas Bamman where researchers took people with Parkinson’s disease and ran them through a high-intensity exercise program, finding that you could not only help people preserve some function but also restore some function. [00:28:52] Ken mentions that despite the awareness of Parkinson’s negative impact on motor function, there has been very little attention paid to its impact on skeletal muscle. Ken asks Kaleen to talk about her study that provided insights into the potential mechanistic roles of skeletal muscle. [00:31:33] Dawn mentions that the research Kaleen just discussed was published in a paper titled “Rehabilitative Impact of Exercise Training on Human Skeletal Muscle Transcriptional Programs in Parkinson’s Disease.” [00:31:51] Kaleen talks about her analysis of the dataset from the 2017 study at UAB that was led by Marcus Bamman.  Kaleen explains how she was able to identify 706 genes that were differently expressed after rehabilitative training, and how this work strengthens our understanding of skeletal muscle as a communicative tissue in exercise, aging, and neurodegenerative disease. [00:33:38] Dawn asks Kaleen to elaborate on how she ended her paper talking about how future research is needed to determine the influence of exercise training on other levels of phenotypes in Parkinson’s Disease and how skeletal muscle may reflect or orchestrate these changes. [00:35:31] Ken asks Kaleen to talk about her plans for a future clinical trial concerning Parkinson’s at IHMC. [00:37:21] Dawn asks about another study Kaleen conducted that looked at why people respond differently to the same exercise. Dawn also asks Kaleen to talk about why the reduction in skeletal muscle mass with advancing age is such a serious issue. [00:39:20] Ken follows up mentioning that sarcopenia is often thought of as a gradual decline in muscle mass, but often it is a process where there will be a slow gradual trend punctuated with large downward spikes as individuals grow older and experience illness and injury over the years. [00:41:01] Ken mentions that for the aforementioned study, Kaleen examined what occurs at the molecular level to shed light on the impact of resistance training on muscle hypertrophy. Ken goes on to explain that, previously, the UAB lab and others had demonstrated the magnitude of resistance-training-induced muscle hypertrophy is highly variable across individuals, a phenomenon known as interindividual response heterogeneity. [00:43:07] Dawn mentions that Kaleen used two algorithms to assess the evidence of gene networks that link muscle building to gene expressions. Dawn asks why Kaleen decided to proceed this way, and what future research possibilities does this method open up. [00:45:20] Ken asks about the possibility that Kaleen’s study leaves open the idea that exercising in the past leaves a molecular footprint, creating a kind of “muscle memory” that can come back to help us as we age, even if we haven’t kept up the habit of exercise. [00:54:39] Dawn mentions that Kaleen’s 2019 study on the effects of aging and lifelong aerobic exercise on inflammation supports other recent evidence that training is anti-inflammatory. Kaleen explains that the lifelong habit of exercise offers protection against “inflammaging,” which is the experience of chronic low-grade inflammation throughout the aging process. Dawn asks, however, if people who have waited till their 30s or 40s to begin the habit of exercise have passed the window of opportunity to benefit from the protective therapeutic factors that regular training confers. [00:55:55] Dawn explains that Kaleen was recently the lead author of a paper that appeared earlier this year in Comprehensive Physiology titled, “State of Knowledge on Molecular Adaptations to Exercise in Humans.” Dawn explains that this paper was a comprehensive look at the current literature surrounding the molecular and cellular processes underlying exercise-induced benefits and adaptations in humans. Dawn asks Kaleen to explain how the study of exercise as a preventative and therapeutic treatment has been rapidly gaining momentum for the past couple of decades. [00:57:58] Dawn mentions that the National Institutes of Health decided to fund a trial to look at the effects of exercise at the molecular level across a large group of people to build what they’re calling the Molecular Map of Exercise. Dawn asks Kaleen to talk about the consortium that the NIH is funding for this trial, and how Kaleen’s paper ties into that. [01:01:46] Ken asks what kind of response this review paper has received from the broader community. [01:02:49] Ken mentions that Marcas Bamman, who is helping spearhead IHMC’s new Healthspan, Resilience and Performance Complex, recruited Kaleen to become part of this initiative. Ken asks Kaleen what attracted her about this project. [01:04:15] Dawn mentions that Kaleen is heading up a lot of the computational work at IHMC to help the institute’s researchers gain insight into why some people respond better to exercise than others on a molecular level. Dawn goes on to mention that Kaleen is currently working on a number of ongoing projects and asks her to talk about how her work plays into all this research. [01:05:44] Kaleen talks about how it’s essential to have the right tools as researchers’ questions become more complicated. She and a colleague at IHMC recently received funding to enhance what is known as a pathway-level information extractor, a tool more commonly referred to as PLIER. Kaleen talks about how the funding for this project will allow IHMC to build up its algorithm potential and open the door for IHMC researchers to handle higher dimensions of data.   [01:07:48] Dawn asks about a paper by a group of researchers out of the Swedish School of Sport and Health Sciences in Stockholm, which examined acute molecular responses to concurrent exercise involving different muscles. [01:09:56] Ken asks if Kaleen thinks that her type of muscle fiber, which is highly skewed toward Type I, has anything to do with her gravitation towards endurance sports [01:11:39] Ken talks about the shift in muscle fiber type seen in the aging population where fast twitch fibers are lost first, leading to some older people maintaining strength but losing explosive power. [01:13:20] Dawn asks if there is a triathlon in Kaleen’s future. [01:14:02] Dawn asks Kaleen about the influence of muscle-fiber type on performance and how that might influence someone in terms of them gravitating toward a particular mode of exercise. [01:15:41] Dawn closes the interview asking about Kaleen’s passion for singing and how she now sings in her church choir. Links: Kaleen Lavin bio Learn more about IHMC STEM-Talk homepage Ken Ford bio Ken Ford Wikipedia page Dawn Kernagis bio