Unlocking the Potential of a Century-Old Approach: Ketogenic Diets and Aging

Introduction

A century ago, pediatricians introduced the ketogenic diet as a treatment for children with intractable seizures, alongside its use in managing diabetes. This dietary approach, characterized by low-carbohydrate, high-fat meals, aimed to induce a state of near hypoglycemia, forcing the body to rely on ketones for energy. Although this strategy faded with the discovery of insulin and better antiseizure medications in the 1920s, it's making a comeback today, thanks to rising concerns about obesity and diabetes. The global market for ketogenic diets surged to over $11 billion in 2022, raising a pivotal question: is this resurgence just another fad, or have we finally caught up with a century-old approach?

Ketogenic Diets and Their Historical Efficacy

While the reasons behind the effectiveness of ketogenic diets in controlling seizures remain unclear, researchers have established their effectiveness in treating diabetes and metabolic syndrome. Athletes have also experienced positive outcomes. Still, the scope of their potential benefits, particularly in conditions like heart disease and dementia, remains less explored. However, recent developments, including a $3.5 million federal grant from the National Institutes of Health for the TAKEOFF trial, suggest that we are on the verge of unlocking the true potential of ketogenic diets in addressing various aspects of aging and frailty.

The TAKEOFF Trial: Targeting Aging with Ketone Ester

The TAKEOFF trial (Targeting Aging With Ketone Ester in Older Adults for Function in Frailty) aims to understand the long-term effects of ketone ester supplementation on frailty. Ketone esters, precursor molecules that rapidly convert into ketone bodies in the absence of carbohydrates, hold promise as a potential tool to combat aging-related frailty. The study involves collaboration between researchers from the Buck Institute for Research on Aging, Ohio State University, and the University of Connecticut, with a total of 180 participants.

Frailty and Aging

Frailty, a common condition associated with aging, involves the gradual loss of strength, endurance, and resilience to stressors. This condition often leads to increased susceptibility to falls, slow recovery from surgery, and reduced mobility. The TAKEOFF study's primary hypothesis is that by targeting fundamental aging mechanisms, it may be possible to mitigate various age-related diseases across different organ systems.

The BIKE Pilot Study

Before launching the TAKEOFF trial, researchers at the Buck Institute conducted the BIKE (Buck Institute Ketone Ester) pilot study. This was the first double-blind, randomized, placebo-controlled study assessing the use of ketone ester supplements in adults aged 65 and older. The 12-week BIKE study provides valuable insights to help fine-tune the protocol for the longer-term TAKEOFF trial, which is expected to last up to 24 weeks.

Study Outcomes and Biomarkers

The primary outcome measure across all three study sites in the TAKEOFF trial will be leg press strength. Researchers will also evaluate various secondary outcomes related to geriatric and cognitive function, including gait speed, cognitive tests, and overall quality of life. Additionally, biomarkers available in clinical labs, such as insulin, C-reactive protein, cystatin, and natriuretic peptide, will be studied as potential responsive outcome measures for future aging research.

Wide-ranging Expertise in Ketone and Aging Research

The TAKEOFF trial boasts a team of co-investigators with diverse expertise in ketone and aging research. Dr. Jeff Volek from Ohio State University, known for his work on ketogenic diets and supplements, brings insights into the anti-catabolic effects of ketones on muscle tissue. Additionally, ketones' anti-inflammatory properties may offer benefits to older adults by reducing oxidative stress, potentially improving conditions like heart disease, Alzheimer's disease, asthma, and arthritis.

Immunological Perspective on Aging

Dr. Jenna Bartley, an assistant professor at the University of Connecticut, examines how immune responses and physical function decline with age. Ketogenic diets and ketone bodies, particularly beta-hydroxybutyrate, have shown promising influences on various aspects of aging. Dr. Bartley's work explores whether ketone supplementation can enhance immune function, particularly focusing on T cells, which play a crucial role in immune responses. This research may hold the key to addressing immune dysfunction associated with aging.

Benefits of Ketone Supplements

Unlike strict ketogenic diets, which demand rigorous adherence, ketone supplements offer a more accessible and practical approach. They eliminate the need for constant dietary monitoring, potentially making findings from studies like TAKEOFF more applicable to a broader population. Recent advancements in ketone ester formulations have improved taste and affordability, further enhancing their appeal as a research tool.

Conclusion

The TAKEOFF trial and related studies mark significant steps in the emerging field of geroscience, aimed at translating fundamental aging mechanisms into therapies for age-related diseases. As we continue to explore the molecular mechanisms of frailty and aging, ketogenic diets and supplements, once regarded as relics of the past, could emerge as powerful tools for promoting healthy aging and addressing a wide range of age-related conditions. While more research is needed, the potential benefits of ketone supplementation are generating optimism among researchers, offering hope for a healthier and more active aging population.