Can achieving beneficial ketone levels improve metabolic health in the military?

A series of upcoming studies will explore whether the routine of active-duty military life and veterans’ disproportionately high incidence of chronic disease could be controlled by lifestyle interventions designed to achieve a metabolic state of nutritional ketosis.

This work, led by Ohio State University exercise science Y biomedical researchersis funded by a $10 million grant from a US Department of Defense program focused on improving the health of military service members, veterans, and the American public.

“Many Americans, including a significant number of military service members, and especially veterans, suffer from poor metabolic health,” the lead researcher said. jeff volekProfessor of human Sciences in the state of Ohio. “Despite billions of dollars in investments from the public and private sectors, traditional drug and lifestyle treatments have had limited success in reducing complications attributed to poor metabolic health, including disorders of the sleep, obesity, type 2 diabetes, heart failure, and chronic kidney disease. .

“We hope that everything we find here will have great relevance across the board, both inside and outside the military.”

More than two decades of studies have included Volek’s findings that the very low-carb, high-fat ketogenic diet, which converts fat into ketones used by cells in the body and brain as an alternative to glucose, does not raise saturated fats in the bloodto be able to help endurance athletes burn fat and keep the promise keep soldiers fit for duty. The popularity of the diet and the scientific evidence of its health benefits and weight loss results have led to the development and marketing of products that can be ingested to rapidly raise blood ketones without changing eating habits.

“A large portion of the grant is looking at both strategies to increase ketosis: the ketogenic diet and ketone-based beverages,” Volek said. Ketone drinks, formulated as ketone esters, are designed to put the body into nutritional ketosis, the state of the human body when it has increased access to ketones for fuel and as a signaling molecule.

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“Does the ketogenic diet produce different effects than ketone esters? Is one better than the other? My work has found that the ketogenic diet provides significant health benefits, but there could be some health benefits attributed to taking ketones and not changing the diet. It is a completely new area of ​​research.”

Orlando Simonetti

Studies exploring the impact of ketone esters on blood ketone levels and factors influencing individual variation in response to their intake are one of four separate project areas to be run simultaneously. The other three are intended to further understanding of nutritional ketosis in the context of addressing life circumstances and health issues of particular concern to the military: inadequate sleep, chronic kidney disease, and heart failure.

“This will be the first work to specifically explore how ketone esters and a ketogenic diet impact clinical outcomes, such as heart function and exercise capacity, in heart failure patients,” he said. Orlando SimonettiProfessor of cardiovascular medicine at Ohio State and co-leader of one of the projects. “We are hopeful that the imaging and physiological performance data we collected in this study will pave the way for future research on nutritional ketosis as a prevention and treatment for cardiovascular disease.”

All branches of the military are affected by poor metabolic health in the general population, which complicates recruitment, reduces soldier readiness, and can harm post-service quality of life. Disrupted sleep and the variety of stressors associated with training and active duty can have combined effects on both the body and the brain, increasing the risk of obesity and reduced mobility, as well as more serious mental health and neurological problems. forward in life.

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The grant, a DOD Peer Reviewed Medical Research Program – Focused Program Award, is called STAK, short for Strategies to Increase Ketosis. Volek’s lab leads the coordination of the work. the Buck Institutean aging research company, and virtual healtha company co-founded by Volek that has created a nutritional therapy program to treat and reverse type 2 diabetes on a large scale, has received sub-awards under the STAK grant for providing additional expertise.

STAK is intended to improve military readiness and reversal of diseases across the metabolic spectrum, from obesity/prediabetes to type 2 diabetes and associated complications of heart failure and chronic kidney disease.

The funding supports four projects:

  • Optimizing Ketone Administration Strategies: Clinical studies will explore the dosage, formulation, and timing of administration of ketone esters, as well as markers of health in study participants, to measure the physiological and metabolic effects of ketone esters. supplements. The researchers aim to create evidence-based guidelines for the use of ketone ester compounds based on the individual characteristics and performance requirements of soldiers. Volek’s lab will partner with the Buck Institute on this project.
  • Ketone Resistance Against Sleep Restriction: High-quality sleep is key to military mission readiness and success, but it’s not always possible to achieve in the field. This trial will assess the extent to which ketone esters and a ketogenic diet reduce the detrimental effects of sleep loss on physical and cognitive performance in ROTC cadets under physically demanding conditions. project leader william kramerin human sciences at Ohio State, he will work collaboratively with Ohio State sleep and brain imaging specialists.
  • Ketone Therapy to Improve Exercise Tolerance in Heart Failure: Simonetti, a frequent research collaborator of Volek, will co-direct this project with the Ohio State Wexner Medical Center cardiologist yuchi han. The team will examine the effects of ketone esters and a ketogenic diet in patients with type 2 diabetes and heart failure with preserved ejection fraction, a type of disease characterized by typical symptoms of heart failure despite almost no blood-pumping ability. normal heart. A randomized, double-blind, crossover trial will compare exercise capacity and heart function in participants taking ketone esters, following a ketogenic diet, or following a standard mixed-care diet. Ohio State researchers will partner with Virta Health, using the company’s ongoing remote care model to manage patient engagement for six months after trial completion.
  • Delaying or preventing the progression of diabetic nephropathy: Virta Health scientists will lead this two-year longitudinal study, examining whether the continuous remote care model, which includes biomarker monitoring, and a consistently administered ketogenic diet delay or they even reverse progression to chronic kidney disease in veterans with type 2 diabetes.
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Recruitment and enrollment of study participants is expected to begin in early 2023. The ketone esters used in the studies were developed by youth.

Project 1 will be led by brianna stubbs from the Buck Institute. Additional researchers include John Newman from the Buck Institute and Madison Kackley and Teryn Bedell from Volek’s lab.

Additional Project 2 researchers include Scott Hayesassociate professor of psychology, and Ulysses Magalangmedical director of sleep medicine at Ohio State Wexner Medical Center.

Additional Project 3 investigators include physicians from Ohio State Wexner Medical Center Joshua Josephendocrinologist; ayesha hasan, medical director of the heart transplant program; Y Sitaramesh Emanian interventional cardiologist.

Project 4 will be led by amy mackenzie, Robert Ratner Y Stephen Phinney of Virtual Health.

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