Daily consumption of ketone ester, bis-octanoyl (R)-1,3-butanediol, is safe and tolerable in healthy older adults in a randomized, parallel arm, double-blind, placebo-controlled, pilot study
{"title":"Daily consumption of ketone ester, bis-octanoyl (R)-1,3-butanediol, is safe and tolerable in healthy older adults in a randomized, parallel arm, double-blind, placebo-controlled, pilot study","authors":"","doi":"10.1016/j.jnha.2024.100329","DOIUrl":null,"url":null,"abstract":"<div><h3>Objectives</h3><p>Ketone bodies are endogenous metabolites produced during fasting or a ketogenic diet that have pleiotropic effects on aging pathways. Ketone esters (KEs) are compounds that induce ketosis without dietary changes, but KEs have not been studied in an older adult population. The primary objective of this trial was to assess the tolerability and safety of KE ingestion in a cohort of older adults.</p></div><div><h3>Design</h3><p>Randomized, placebo-controlled, double-blinded, parallel-arm trial (NCT05585762).</p></div><div><h3>Setting</h3><p>General community, Northern California, USA.</p></div><div><h3>Participants</h3><p>Community-dwelling older adults, independent in activities of daily living, with no unstable acute medical conditions (n = 30; M = 15, F = 15; age = 76 y, range 65–90 y) were randomized and n = 23 (M = 14, F = 9) completed the protocol.</p></div><div><h3>Intervention</h3><p>Participants were randomly allocated to consume either KE (25 g bis-octanoyl (R)-1,3-butanediol) or a taste, appearance, and calorie-matched placebo (PLA) containing canola oil daily for 12 weeks.</p></div><div><h3>Measurements</h3><p>Tolerability was assessed using a composite score from a daily log for 2-weeks, and then via a bi-weekly phone interview. Safety was assessed by vital signs and lab tests at screening and weeks 0, 4 and 12, along with tabulation of adverse events.</p></div><div><h3>Results</h3><p>There was no difference in the prespecified primary outcome of proportion of participants reporting moderate or severe nausea, headache, or dizziness on more than one day in a two-week reporting period (KE n = 2 (14.3% [90% CI = 2.6–38.5]); PLA n = 1 (7.1% [90% CI = 0.4–29.7]). Dropouts numbered four in the PLA group and two in the KE group. A greater number of symptoms were reported in both groups during the first two weeks; symptoms were reported less frequently between 2 and 12 weeks. There were no clinically relevant changes in safety labs or vital signs in either group.</p></div><div><h3>Conclusions</h3><p>This KE was safe and well-tolerated in this study of healthy older adults. These results provide an initial foundation for use of KEs in clinical research with older adults.</p></div>","PeriodicalId":54778,"journal":{"name":"Journal of Nutrition Health & Aging","volume":null,"pages":null},"PeriodicalIF":4.3000,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1279770724004160/pdfft?md5=d1ff78b8a8ab1a599816c22096ac2f48&pid=1-s2.0-S1279770724004160-main.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Nutrition Health & Aging","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1279770724004160","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"GERIATRICS & GERONTOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Objectives
Ketone bodies are endogenous metabolites produced during fasting or a ketogenic diet that have pleiotropic effects on aging pathways. Ketone esters (KEs) are compounds that induce ketosis without dietary changes, but KEs have not been studied in an older adult population. The primary objective of this trial was to assess the tolerability and safety of KE ingestion in a cohort of older adults.
Community-dwelling older adults, independent in activities of daily living, with no unstable acute medical conditions (n = 30; M = 15, F = 15; age = 76 y, range 65–90 y) were randomized and n = 23 (M = 14, F = 9) completed the protocol.
Intervention
Participants were randomly allocated to consume either KE (25 g bis-octanoyl (R)-1,3-butanediol) or a taste, appearance, and calorie-matched placebo (PLA) containing canola oil daily for 12 weeks.
Measurements
Tolerability was assessed using a composite score from a daily log for 2-weeks, and then via a bi-weekly phone interview. Safety was assessed by vital signs and lab tests at screening and weeks 0, 4 and 12, along with tabulation of adverse events.
Results
There was no difference in the prespecified primary outcome of proportion of participants reporting moderate or severe nausea, headache, or dizziness on more than one day in a two-week reporting period (KE n = 2 (14.3% [90% CI = 2.6–38.5]); PLA n = 1 (7.1% [90% CI = 0.4–29.7]). Dropouts numbered four in the PLA group and two in the KE group. A greater number of symptoms were reported in both groups during the first two weeks; symptoms were reported less frequently between 2 and 12 weeks. There were no clinically relevant changes in safety labs or vital signs in either group.
Conclusions
This KE was safe and well-tolerated in this study of healthy older adults. These results provide an initial foundation for use of KEs in clinical research with older adults.
期刊介绍:
There is increasing scientific and clinical interest in the interactions of nutrition and health as part of the aging process. This interest is due to the important role that nutrition plays throughout the life span. This role affects the growth and development of the body during childhood, affects the risk of acute and chronic diseases, the maintenance of physiological processes and the biological process of aging. A major aim of "The Journal of Nutrition, Health & Aging" is to contribute to the improvement of knowledge regarding the relationships between nutrition and the aging process from birth to old age.