First study of ketone body supplementation in healthy older adults will look at ketone ester supplementation in the context of aging.
The Buck Institute for Research on Aging has launched its first human clinical trial. The BIKE (Buck Institute Ketone Ester) pilot study is the first trial in the world to look at the effects of ketone ester supplementation in the context of aging.
Thirty healthy individuals over the age of 65 will take part in a 12-week double-blind, randomised, placebo-controlled study to see whether benefits of ketone bodies in aging that have been observed in mice translate to human beings.
Longevity.Technology: Keto is very much a weight-loss buzzword, but the science of ketosis has much broader applications for longevity and improving healthspan. Ketones are naturally-occurring compounds made in the liver and are a byproduct of fat metabolism – meaning when your body burns fat for energy, rather than carbohydrates. Carbs are the body’s go-to for energy, so there is usually only a very small amount of ketones in the blood at any given time. However, when dietary carbohydrates (sugars in various forms) are limited, the body uses fat instead of sugar for energy.
This state of ketosis can be achieved through fasting, and ketogenic diets have become popular in recent years. But as well as weight loss, ketosis has several health benefits, including a reversal of metabolic syndrome and reduced inflammation.
Ketogenic diets have been extensively studied in mice; previous research at the Buck showed that a ketogenic diet improved healthspan and memory in aging mice, but it’s easy to control what a lab mouse eats – and harder for humans to resist the siren call of the carbohydrate. In addition, health concerns have been raised about eating high amounts of fat and limiting the intake of carbohydrates.
Enter the ketone ester supplement – able to put people into ketosis without a restrictive diet. Several clinical studies are underway testing the use of ketone esters in people with heart disease, type 2 diabetes, obesity and memory deficits, among other conditions.
Just like riding a BIKE
The new pilot study, which is a basic experimental study involving humans, not an investigational drug study, is recruiting participants from Marin County in California. Participants should be independent older individuals with stable health, aged 65 years or older, who have access to the internet and can easily be involved in a 12-week programme.
“We are the first research organization in the world to test the impact of a ketone ester on aging mechanisms in older adults,” said Buck assistant professor John Newman, MD, PhD, who is the principal investigator of the study. “We are excited to push cutting-edge aging science discovered in our laboratory and others toward clinical application and are thrilled to be doing it together with people who live in Marin County.”
Newman explains that findings in the lab have suggested that ketone bodies impact many of the pathways associated with aging, so the team hopes this research will verify that in humans , laying the groundwork for the next big steps.
He said: “The hardest step in moving discoveries out of the laboratory is that first proof-of-principle: does the biology hold up in people? By growing the capability to do small, cutting-edge clinical studies at Buck we can give Buck scientists and the Marin community the ability to really unlock the Buck’s scientific potential together.”
“This first-ever human clinical trial is a landmark event at the Buck Institute. It’s a hallmark of our growth and the maturation of the field of aging research,” said Buck Institute President and CEO Eric Verdin, MD.
“This effort is an important advance in its own right, but it is also a seed to grow the expertise and capabilities to accelerate unlocking the potential of Buck science to improve human health. The trial was funded by members of our local community and we are looking forward to engaging with local organizations such as Vivalon and the Marin Council on Aging to ensure community involvement and diverse, inclusive, and equitable participation as our clinical studies grow.”
Buck Lead Translational Scientist Brianna Stubbs, DPhil, is managing the BIKE study. Those enrolled in it will be paid for their participation. They will take a daily study beverage with half of the participants getting the ketone ester, the others getting a placebo. Study personnel will not know which participants are getting the actual ketone supplement.
Participants in the study will make five visits to the Buck, and at home they will fill out daily activity logs and wear a supplied Fitbit. Blood and other bio-specimens will be collected at various times during the trial and participants will be asked to perform standardised physical function tests involving balance, walking speed, chair sits, leg press performance, walking speed and grip strength. They will also take standardised mental tests which measure short-term memory, visuospatial abilities, executive functions, attention, concentration and working memory as well as orientation to time and place. Study data will be available after all results are analysed.
Also in the pipeline
Stubbs and Newman have applied for funding to expand the pilot study to involve 180 people at risk for frailty at three sites across the US in a study called TAKEOFF ( Targeting Aging with a Ketone Ester for Function in Frailty). This study would look at the impact of ketone esters on the aging immune system, and on muscle function and metabolism, and would analyse state-of-the-art geroscience biomarkers for the entire study.
Also underway is STAK (Strategies to Augment Ketones for Enhanced Readiness and Disease Reversal) which is funded by the Department of Defense and run by Ohio State University. The overall goal is to determine if ketone esters would promote resilience in active duty soldiers as well as support the health of veterans; recruitment for STAK is expected to start next month.=