Ketones in a Ketogenic Diet for Type 2 Diabetes and Heart Failure

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