Episode 167: Nicholas Norwitz discusses a ketogenic diet as metabolic medicine
STEM-Talk
Understanding Lean Mass Hyper-responders and Lipid Energy Model
Exploring the concept of lean mass hyper-responders characterized by high LDL, high HDL, and low triglycerides, the chapter delves into the lipid energy model and the mechanisms behind this lipid profile. Discussions include the limitations of using BMI to categorize individuals and the importance of considering other metrics like DEXA scans. Emphasizing the individual context and dynamic nature of lipid profiles, the conversation highlights the complexities of interpreting biomarkers like HDL and LDL in the metabolic responses to diet and exercise.
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 found to have low fat mass as a defining feature, how might this effect the lipid panel in terms of LDL-C.
[00:50:50] Ken explains that the thinking regarding HDL is currently being refined, with current ideas regarding HDL all-cause mortality currently conforming to a U-shaped curve. Ken asks, with respect to lean mass hyper-responders, what sort of health risks these high HDL levels might confer.
[00:53:50] Marcas asks Nick how the lipid-energy model would apply in the population of lean people with respect to the difference between untrained individuals and highly trained athletic people, and if he can envision a study to tackle that question. Marcas goes on to ask when Nick thinks would be the best time to acquire samples in this hypothetical study, relative to bouts of exercise.
[00:57:55] Marcas mentions that the European Society of Cardiology and the European Society of Atherosclerosis came out with a consensus in 2019 on the superiority of apolipoprotein B measurement of serum cholesterol levels as an indicator of risk. Marcas goes on to mention that while apolipoprotein B was not measured in Nick’s Oreo study, his high LDL measurement was correlated with a high LDL particle count, meaning that lean-mass hyper responders might have a high apolipoprotein B and or high-particle count, which could translate to risk for cardiovascular disease. Marcas asks Nick what his thoughts are on how people on low carb diets should navigate high apolipoprotein B levels.
[01:01:09] Marcas pivots to ask about a piece that Nick wrote on a website called Stat, which is a journalistic site covering health, medicine, and life science. The piece detailed Nick’s concern going into medical school that being on the ketogenic diet would make him something of a pariah. Marcas asks how his experience in med school is now three years later, and whether or not he is in fact a pariah.
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