STEM-Talk Dawn Kernagis and Ken Ford

Today we have Dr. Nicholas Norwitz, 28, a third-year Harvard Medical School student whose research into the applications of a ketogenic diet as metabolic medicine has attracted a significant following.

For a number of years during his youth, Nick suffered from a number of debilitating diseases, including osteoporosis, ulcerative colitis, and inflammatory bowel disease.  In today’s interview, we talk to Nick about research that led him to adopt a ketogenic diet that put him back on the road to metabolic health.

After graduating from Dartmouth College in 2018 with a degree in cellular and molecular biology, Nick attended Oxford University where he earned a Ph.D. in metabolism and nutrition. He is the author of peer-reviewed scientific papers and textbook chapters on topics including Alzheimer’s disease, cardiovascular disease, diabetes, gastrointestinal health, genetics osteology and Parkinson’s disease.

Show notes:

 [00:02:53] Marcas opens the interview mentioning that Neck grew up in Boston, and asks if it’s true that he was a very curious kid growing up.

[00:04:09] Marcas asks Nick if as a young child he always knew he wanted to be a physician and a scientist.

[00:05:40] Ken mentions that Nick was a runner in high school, and as is the case with many runners, this led to fractures. However, Ken goes on to say that these fractures did not resolve for Nick, and asks what he learned as a result.

[00:11:08] Ken asks about Nick’s eating habits in college as he loved to cook and bake.

[00:15:40] Marcas follows up, asking Nick at what point during his Ph.D. training was he admitted to palliative care.

[00:21:01] Marcas pivots to talk about the need for incorporating metabolic health into our health-care system. He mentions that Nick once said that “we live in a society where our social norms and ecosystem, with respect to health and food, are extremely dysfunctional,” and asks Nick to elaborate on this.

[00:26:16] Ken mentions a paper that Nick recently published titled, “Oreo Cookie Treatment Lowers LDL Cholesterol More Than High Intensity Statin Therapy in a Lean Mass Hyper-Responder on the Ketogenic Diet: A Curious Crossover Study.” To provide some background, Ken mentions that some people on a ketogenic or low carb diet experience a dramatic increase in LDL cholesterol. The rationale behind Nick’s paper being that if it is the removal of carbohydrates that causes this increase in LDL, adding carbohydrates back into one’s diet should bring LDL levels back down. Ken asks Nick to talk about this experiment and how he designed it.

[00:35:44] Ken mentions that the paper seems to be designed to be provocative, as simply testing carbohydrates against statins would likely have not gotten as much attention as using Oreo cookies.

[00:37:00] Marcas mentions that in the Oreo cookie vs statin experiment, Nick’s original fasted-morning LDL was 384, before dropping it with Oreos, then doing a washout before dropping it again with statins. Marcas asks Nick what his fasted-morning LDL was post washout, prior to the statin intervention.

[00:39:07] Marcas brings up Nick’s paper titled: “The Lipid Energy Model: Reimagining Lipoprotein Function in the Context of Carbohydrate Restricted Diets.” Marcas goes on to mention that the aim of the paper was to propose a mechanistic explanation for the “lean mass hyper-responder phenotype.” Marcas asks Nick to give listeners an overview of the lipid-energy model.

[00:45:18] Ken mentions that according to Nick, BMI is not a requirement for classification as a lean mass hyper-responder. Nick’s paper, however, uses BMI data. Ken mentions that he finds BMI relatively useless and asks why Nick did not use DEXA scans instead.

[00:48:52] Ken mentions that adipose tissue contains roughly 25 percent of total body cholesterol, and we know that LDL binding to adipose cell membranes is competitively inhibited by HDL. Ken asks if lean mass hyper-responders were foun

Dr. Vyvyane Loh returns to STEM-Talk for her second appearance to talk about atherosclerotic heart disease. Also known as ASCVD, the disease has been reported to affect 26 million people in the U.S., and annually leads two million hospitalizations and more than 400,000 deaths.

Vyvyane is a board-certified physician in obesity and internal medicine. In episode 142 of STEM-Talk, we talked to Vyvyane about her Boston-based preventative-care practice that specializes in weight management and the treatment of chronic metabolic diseases such as diabetes, hypertension and dyslipidemia.

In today’s podcast, Vyvyane and host Dr. Ken Ford talk about ASCVD as well as recent research that has shown substantial individual variability in the response to statin therapy as a way to lower cardiovascular risk. Vyvyane and Ken also discuss how the current knowledge base informing clinical practice in medicine today is far behind advances in the biological sciences, especially in the field of ASCVD.

Show notes:

 [00:03:15] Ken welcomes Vyvyane back to STEM-Talk and encourages listeners to check out Vyvyane’s first interview, episode 142. Ken goes on to mention that atherosclerotic heart disease has been reported to affect 26 million people in the U.S. and that despite the wide use of statins as a primary prevention of atherosclerotic heart disease, the effects of this treatment have been variable with regards to major adverse cardiac events. Ken asks Vyvyane for her thoughts.

[00:05:32] Ken asks Vyvyane about recent developments in atherosclerotic heart disease research, specifically in regard to the anatomical aspects of the disease-model itself.

[00:08:43] Ken follows up asking Vyvyane how the knowledge we have of glycocalyces, and the endothelial lining of the blood vessels, could affect clinical practice.

[00:12:19] Ken asks if there are any other recent updates to the anatomical model of atherosclerotic disease that people should be aware of.

[00:13:09] Ken asks Vyvyane how she would characterize the significance of the tunica intima of the coronary artery.

[00:15:25] Ken asks about the third recent anatomical highlight to blood vessels relevant to the discussion.

[00:19:19] Ken follows up, asking if this is how the vasa vasorum contributes to our understanding of the development of atherosclerosis.

[00:21:05] Ken asks Vyvyane to explain what endothelial dysfunction is and what are its downstream effects.

[00:26:09] Ken asks Vyvyane to expound on the link between atherosclerotic disease and auto-immunity.

[00:31:01] Ken asks, given the link to inflammation, if there have been any therapeutic developments made in the treatment of atherosclerotic disease.

[00:34:54] Ken asks about the vaccine that is being developed for atherosclerosis.

[00:37:53] Ken mentions that another recent development in the field is the growing appreciation for clonal hematopoiesis in atherosclerosis. Ken asks Vyvyane to explain what clonal hematopoiesis is.

[00:39:55] Ken asks Vyvyane what some actionable takeaways are from our discussion on atherosclerosis that listeners can take home with them.

[00:43:17] Ken asks Vyvyane about her passion for dance, and how much time she invests in that area of her life.

[00:48:11] Ken follows up asking Vyvyane what drives her to pursue dance so passionately.

[00:53:34] In closing the interview, Ken encourages listeners to check out Vyvyane’s podcast as well as her website.

Links:

Vyvyane Loh website

Vlmdrounds.com

Learn more about IHMC

STEM-Talk homepage

Ken Ford bio

Ken Ford Wikipedia page

 

Today we have Dr. Johnathan Edwards, an anesthesiologist and medical practitioner who specializes in human health and optimization. He is perhaps best known for treating mental health conditions with ketamine,  a dissociative anesthetic that is used for general anesthesia, pain relief, depression and epilepsy. John also uses ketamine to help adolescents overcome depression and suicidal ideation.

In today’s interview, we talk about his new book, “The Revolutionary Ketamine: The Safe Drug That Effectively Treats Depression and Prevents Suicide.” More Americans have died from suicide than all the wars since Vietnam. The suicide rate among 10- to-24-year-olds in this country increased 62 percent from 2007 through 2021. As John points out in today’s discussion, most people are not aware that American children between the ages of 10 and 14 are twice as likely to die from suicide than homicide.

Show notes:

[00:02:39] Dawn explains that suicide is a pressing problem in America, with more Americans dying of suicide than from all the wars since Vietnam. She also points out that police and firefighters are more likely to die from suicide than in the line of duty. John then gives an overview of ketamine and its ability to help treat depression and suicidal thoughts.

[00:06:56] Dawn pivots to mention the dark side of ketamine, including ketamine misuse and overdose.  Recent studies have reported a worldwide increase in ketamine misuse and overdoses. Back in October, Mathew Perry, one of the stars of the popular sit-com “Friends,” died from what the Los Angeles cororner described as the acute effects of ketamine. Because this was such a high-profile case, Dawn asks John to discuss the potential adverse effects of ketamine.

[00:13:03] Ken mentions a 2022 study in the American Journal of Drug and Alcohol Abuse that looked at ketamine overdoses and deaths. The study found no cases of overdose or death from ketamine used in a clinical setting as therapy for depression. Ken asks if there is anything John would like to add about ketamine and safety.

[00:13:059] Dawn shifts to talk about John’s background, mentioning that he grew up riding dirt bikes and eventually raced bikes professionally.

[00:15:18] Ken asks John to share his story of how a junior college professor sparked his interest in science.

[00:17:49] Dawn mentions that John jumped around from Eastern Virginia Medical School, to the University of Reno, to the University of Utah, at which point it looked as though he was heading for a career in internal medicine. Dawn asks why John changed his mind and decided not to pursue that career path.

[00:19:40] Dawn asks John what led him to the University of South Florida.

[00:20:18] Ken asks John about another career shift that came about as the result of a suggestion from one of John’s professors.

[00:21:42] Dawn asks about John’s motivation to move to Las Vegas to be close to his father.

[00:22:59] Dawn asks John to explain what motivated him and his wife to move to France after their daughter turned five.

[00:24:55] Dawn asks John to talk about the transition of ketamine from anesthetic to antidepressant.

[00:28:16] In his book on ketamine, John writes about how the benefits of supervised psychedelic therapy can be broken down into four effects. Ken asks John to briefly explain each of these effects.

[00:31:39] Dawn asks John to explain how ketamine manipulates the function of brain receptors as an antagonist and agonist.

[00:33:40] Dawn mentions that some people do not believe that ketamine functions as a classic psychedelic like psylocibin or LSD. She asks John if he agrees.

[00:35:54] Ken mentions a recent STEM-Talk interview with Mark Mattson discussing glutamate. In Mark’s book, “Sculptor and Destroyer: Tales of Glutamate,” he points out that ketamine’s highest interactions are with glutamate, and this affinity has been shown to alleviate depression and schizophrenia.

What if the path to delaying the onset of dementia symptoms begins at the nose?

It is a doorway that the research of Dr. Michael Leon opened with a 2023 study on the power of olfaction enrichment to influence memory function and brain health. The findings drew wide acclaim and interest when his results found that stimulation of our sense of smell with essential oils had a profound impact on memory, cognition, and language recall.

Our conversation with Leon on STEM-Talk Episode 164 is available now wherever you enjoy podcasts.

Leon’s long research career has focused on the influence of environmental enrichment on neurological function, disease, and disorders. He has studied the benefits of sensory-motor stimulation for children with autism spectrum disorder, for the treatment of anorexia and for those with dementia and neurological conditions.

He is a professor emeritus in the Department of Neurobiology and Behavior at the University of California Irvine, where his Leon Lab has focused on studying the benefits of increased sensory-motor activity in children with autism spectrum disorder.

The work that the Leon Lab is doing is fascinating, and the applications this olfaction stimulation study are potentially important and wide-reaching.

Overview:

[00:02:33] Dawn starts the interview by asking Michael how he got interested in science.

[00:003:59] Dawn asks how Michael got involved in studying olfaction.

[00:04:36] Dawn asks about Michael’s research on Autism Spectrum Disorder (ASD), which resulted in a series of studies from 2013, 2015, and 2016.

[00:08:11] Dawn asks how Michael took the principles of environmental enrichment from his work on autism and applied them to his aging research, which began in 2018.

[00:09:28] Ken asks Michael about his 2023 study titled “Olfactory enrichment using an odorant diffuser improves memory and modifies the uncinate fasciculus in older adults.”

[00:11:25] Ken asks Michael why he chose the specific seven odors that he used in the study.

[00:12:24] Ken poses a listener question about whether or not a CPAP machine, which many older Americans use, would complicate Michael’s olfactory enrichment protocol, or if it is possible that the CPAP machine and the protocol can be used together.

[00:13:35] Dawn asks Michael what the selection and recruitment process was like for this study.

[00:14:48] Ken asks, in light of Michael’s research on the connection between memory and olfaction, what the potential consequences might be for people who reported loss or diminishing sense of smell following a COVID-19 infection.

[00:16:51] Ken asks if any of the olfactory remediation kits have shown promise in restoring lost olfaction following COVID-19.

[00:17:32] Ken asks what the mechanism is behind the loss of olfaction following menopause.

[00:19:43] Dawn asks Michael how his olfactory enrichment as a memory intervention compares to other memory interventions like dancing, music and audio books.

[00:20:22] Ken asks Michael what the limitations of the study were, as well as what kind of follow up he is planning.

[00:23:14] Ken asks if there is any promise in applying Michael’s olfactory therapy to mild TBI.

[00:24:10] Dawn asks Michael to describe how the brain processes information while asleep versus while awake, and if this influenced his study.

[00:25:53] Dawn mentions that the participants of Michael’s 2023 study were healthy, with no signs of dementia. She then asks Michael if he can speak to the potential use of olfactory enrichment for adults living with a dementia diagnosis.

[00:26:41] Ken asks if this olfactory enrichment approach is efficacious for Alzheimer’s and other forms of dementia.

[00:27:10] Ken mentions the difficulty in treating Alzheimer’s pharmacologically due to the varied causes of the disease among individuals.

[00:29:10] Ken asks Michael if there are environmental protocols other than olfactory enrichment that s...

Today we have Dr. Mark Mattson, an adjunct professor of neuroscience at Johns Hopkins School of Medicine who is making his third appearance on STEM-Talk.

Today’s interview focuses on Mark’s research into glutamate and comes on the heels of the publication of Mark’s new book, “Sculptor and Destroyer: Tales of Glutamate – The Brain’s Most Important Neurotransmitter.”

Today Mark explains how more than 90 percent of the neurons in the brain deploy the little-known molecule glutamate as their neurotransmitter. Glutamate controls the structure and function of the brain’s neuronal networks and mediates many of our human capabilities, such as learning, memory, creativity, and imagination.

But there’s also a dark side to glutamate. Mark shares how it can play a causal role in the development of disorders such as autism, schizophrenia, and epilepsy as well as diseases such as Alzheimer’s, Parkinson’s, and ALS.

Mark is affectionally known as the godfather of intermittent fasting and his first appearance on STEM-Talk focused on the many ways that fasting optimizes healthspan and even lifespan. His second STEM-Talk interview followed the publication of his book, “The Intermittent Fasting Revolution: The Science of Optimizing Health and Enhancing Performance.”

Show Notes:

[00:04:05] Dawn welcomes Mark back to STEM-Talk for his third appearance. Dawn mentions that our previous two episodes with mark focused on intermittent fasting, and that Mark is considered the godfather of intermittent fasting. Dawn goes on to mention that the National Institutes of Health has described Mark as “one of the world’s top experts on the potential cognitive and physical health benefits of intermittent fasting.”

[00:05:05] Ken mentions that in our previous STEM-TALK interview Mark shared that he was working on a new book about glutamate. Ken adds that Mark considers his research on glutamate to be his most important work. Ken asks why Mark feels as though this research is his most important, given his substantial contributions in other areas.

[00:05:49] Dawn mentions that Mark’s research hasn’t been limited to just glutamate and intermittent fasting. Mark has contributed to a broad range of topics including brain evolution, cognition, the impact of diet and lifestyle on brain health, as well as the pathogenesis and treatment of various neurological conditions. Dawn asks Mark to talk about his motivation to understand how the pieces of the “brain puzzle” fit together, which is the core motivation for his pursuing a broad scope of research.

[00:07:22] Ken asks about Mark’s postdoc work, where he discovered that glutamate sculpts the formation of hippocampal neuronal networks during development.

[00:09:33] Ken mentions that while Mark was at the University of Kentucky, he discovered that the amyloid beta peptide which accumulates in the brain during Alzheimer’s disease renders neurons vulnerable to excitotoxicity. Ken goes on to say that since this, and the previously mentioned discovery, neurologists have shown that neuronal network hyperexcitability occurs early in Alzheimer’s and may contribute to neuronal degeneration. Ken asks Mark to talk about the significance of these two discoveries.

[00:13:39] Dawn asks Mark to talk about the significance of glutamate as a molecule and how it controls the formation of nerve cell networks as the brain develops in utero.

[00:17:50] Ken asks Mark why he thinks that glutamate rarely comes up in discussions of neurotransmitters, despite its importance of its functions.

[00:19:58] Ken asks Mark to expound on the “dark side” of glutamate.

[00:26:04] Dawn mentions that we may never know where in the universe glutamate originated, and while it might have been here on Earth, it perhaps originated somewhere else in the universe. Dawn asks Mark to expand on that notion.

[00:28:33] Ken shifts to the history of glutamate research, explaining that up until the 1940’s

Today we have Dr. Marc Hamilton, an international expert in muscle physiology. He has published pioneering work on the soleus push-up, a potent physiological method which Marc discovered having the ability to elevate metabolism for hours, even while sitting.

As a professor of Health and Human Performance at the University of Houston, Marc’s research focuses on solving problems of metabolism and biochemistry. His lab currently has a number of ongoing investigations, including studies on the biochemical mechanisms that may optimize fat metabolism to fuel muscle when fasting between meals.  This research includes a look at maximizing glucose metabolism while also reducing related plasma hyperinsulinemia due to chronic inflammation and carbohydrate ingestion.

Another recent area of research focus has been to improve metabolic health for preventing diabetes and pre-diabetes. This includes the goal of improving glucose tolerance. Research has shown that glucose intolerance has been a particularly troubling metabolic problem and has proven to be more difficult to treat than most people realize.

Marc is also well known for a string of papers beginning in early 2000’s that found excessive sitting should be viewed as a serious health hazard. This research illuminated how metabolic and biochemical processes are significantly impacted by certain types of prolonged muscular activity and inactivity.

In today’s interview, we particularly talk to Marc about his paper in iScience that reported that the soleus push-up’s ability to sustain elevated oxidative metabolism to improve the regulation of blood glucose is more effective than many popular methods currently touted as a solution.

Show notes:

[00:02:48] Marc begins the interview talking about his childhood and growing up outside of Houston.

[00:03:49] Ken asks if Marc’s later affinity for the real-world scientific problems that he works on today was originally inspired, in part, by his childhood history of hunting and studying animal behavior and anatomy.

[00:05:20] Marcas asks Marc what other hobbies he had as a child.

[00:06:35] Marcas mentions that Marc didn’t go to college with the intention of becoming a scientist and asks Marc what he had in mind when he started his undergraduate studies at the University of Texas.

[00:09:08] Marcas asks Marc if there was anything in particular in his zoology undergrad that sparked an interest in pursuing a master’s degree in exercise physiology.

[00:10:15] Marcas asks Marc to talk about what he enjoyed the most about graduate school, particularly with his Ph.D. at the University of South Carolina.

[00:16:05] Ken asks if Marc had a great deal of independence with his PhD.

[00:17:27] Ken mentions that Marc went to the University of Texas School of Medicine in Houston for his postdoc research, which focused on physiology, cell biology, and pharmacology. Ken asks Marc what that time was like.

[00:19:45] Ken asks Marc to talk about some fundamentals of muscle metabolism that listeners should keep in mind before diving deeper into his current research.

[00:24:58] Marcas shifts to talk about Marc’s 2004 paper “Exercise Physiology vs Inactivity Physiology,” which focused on the enzyme lipoprotein lipase (LPL) and how periods of inactivity impact its regulation.

[00:32:05] Ken mentions that Marc published a string of papers after his previously mentioned 2004 paper, elaborating on the same theme. Ken brings up his 2008 paper, titled “Too Little Exercise and Too Much Sitting,” in particular. Ken asks Marc to talk about his conclusion in that paper, that excessive sitting should be viewed as a serious health hazard. Ken also asks Marc if there is any efficacy to standing desks and balance boards that one sees in many workplaces now.

[00:36:48] Marcas wonders if over the course of Marc’s research if he has seen any differences in the effects of inactivity across the sexes and asks Marc if the effects are roug...