Marin County’s Buck Institute conducts human trial on dietary supplement

In its first human clinical trial, the Buck Institute for Research on Aging in Novato is studying the effects of a dietary supplement on aging.

"This first-ever human clinical trial is a landmark event at the Buck Institute," said Buck Institute chief executive Eric Verdin. "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."

Thirty Marin residents 65 or older are being recruited to participate in the 12-week, double-blind, randomized, placebo-controlled study. To be considered, email BIKE-Study@buckinstitute.org.

The supplement, a ketone ester, produces the same effect as adhering to a ketogenic diet, which features high-fat, moderate-protein and low-carbohydrate foods. The celebrity psychologist Jordan Peterson has extolled the benefits of his own version of the keto diet, which mostly includes meat.

A ketone body is a compound made in the liver when fat is metabolized. Various forms of fasting and a ketogenic diet both result in the production of these ketones. Ketone production has been linked to several health benefits: weight loss, reduced inflammation and a reversal of the metabolic syndrome, a cluster of conditions that together raise the risk of coronary heart disease, diabetes, strokes and other serious health problems.

"We are the first research organization in the world to test the impact of a ketone ester on aging mechanisms in older adults," said Dr. John Newman, a Buck Institute professor who is the principal investigator of the study.

There are problems with using either fasting or a ketogenic diet to generate ketones in humans. Most people are unwilling to fast for prolonged periods, and there are health concerns associated with eating high amounts of fat and severely limiting the intake of carbohydrates.

The use of the ketone ester supplement avoids those problems because it causes the liver to generate ketosis without fasting or eating high amounts of fat.

Participants in the study will make five visits to the Buck Institute, fill out a daily activity log at home and wear a supplied Fitbit monitor. Blood and other bio-specimens will be collected at various times during the trial.

Newman said biochemical molecular effects on inflammation, metabolism and the biomarkers of aging will be assessed. Participants will also be asked to perform standardized physical and mental tests to determine if the ketone ester affects their strength, mobility and cognitive function.

Study nurses and independent medical officers will perform routine clinical labs to ensure that the ketone ester is safe for each participant.

Newman said the 2.5-ounce ketone ester people will drink once a day "has a 'generally recognized as safe' designation from the Food and Drug Administration and is sold to consumers as a food product, similar to a dietary supplement."

"I've been floored by the response from the community to this," he said, noting that half a dozen participants have already signed up. "We're getting dozens of emails a day."

The pilot study is being funded by philanthropists. Kentfield resident Jim Johnson, a retired plastic surgeon, donated $250,000 to the project, and the Buck Institute's "impact circle," a group of Marin residents who contribute regularly to Buck projects, chipped in $120,000.

Johnson, 75, said that during the early 2000s he was involved in research studying the health effects of fasting on alternate days and was excited to learn that the Buck was investigating the means of producing similar beneficial effects using ketone esters.

Johnson said he experimented with eating just 20% of his normal diet on alternate days but found the regimen difficult to maintain. He said he has been taking the ketone ester being used in the study for the last year and actually doubled the dose a month ago.

Johnson said he seems to have more mental energy and believes his endurance has improved, but added, "I'm not ruling out the placebo effect."

The Buck Institute, Newman and Dr. Brianna Stubbs, a study investigator, own stock in BHB Therapeutics, the company providing the ketone ester being studied. They are also inventors on patents that relate to the product being studied.

BHB Therapeutics is a joint venture between Juvenescence and the Buck Institute. BHB Therapeutics's focus is novel approaches to inducing a state of ketosis based on research conducted in the labs of Verdin and Newman.

In May 2022, Juvenescence and the Buck Institute announced a new joint venture, Selah Therapeutics, which is focusing on novel ketone-based therapies for chronic diseases of aging.

Newman said collaborations with industry can play a vital role in moving cutting-edge science out of the lab and into products that can benefit people's lives. For example, he said BHB Therapeutics developed the ketone ester and conducted the testing necessary to ensure that it is safe for humans to take.

"That gave us a tool that we could give to people in clinical trials, which we didn't have before," Newman said. "I could never have done that by myself working in the lab."

Newman, however, said researchers have to carefully manage potential conflicts of interest.

"In the aging field, we have to be particularly sensitive to that idea," he said, "because there is so much stuff that is not science out there. So much stuff that is sold as anti-aging or anti-aging clinics. Stuff that is pseudoscience."

Newman said that although BHB Therapeutics is supplying the ketone ester, it is not funding the study and played no role in its design.

"This is just the first of what we hope will be a growing clinical research program at the Buck," Newman said, "to help us accelerate getting our science out of the laboratory and into people's lives."