Study Finds Intermittent Fasting May Offset Alzheimer Disease Risk, Support Treatment Goals

The study may serve as a foundation for future investigation regarding dietary recommendations to support the treatment of Alzheimer disease.

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About the Trial

Trial Name: Intermittent Calorie Restriction, Insulin Resistance, and Biomarkers of Brain Function

ClinicalTrials.gov ID: NCT02460783

Sponsor: National Institute on Aging (NIA)

Completion Date: December 23, 2022

According to findings of an exploratory pilot study published in Cell Metabolism, intermittent calorie restriction improved executive function and other memory measures in older adults who are cognitively intact. The research was also presented in a poster presentation at the 2024 Alzheimer's Association International Conference in Philadelphia, Pennsylvania, which was held July 28 to August 1, 2024.¹

For this study (NCT02460783), investigators assessed whether late middle-age and older overweight individuals who were considered cognitively intact with peripheral insulin resistance (IR) are a population for accelerated cognitive brain aging. The enrolled 40 participants had a mean age of 63.2 years with a body mass index (BMI) of 27.5 or higher (mean BMI: 34.4). Additionally, most of the enrolled participants were women (60%) and were White (62.5%).^1,2

Participants were randomly assigned to adhere to an intermittent fasting (IF; n =20) or “healthy living” (HL; n = 20) diet and followed their assigned diet for an 8-week period. IF consisted of restricting calories to a quarter of the recommended daily intake for 2 consecutive days per week (2 meal replacement shakes adding to a total of 480 calories per day) and 5 days of HL, whereas the HL diet emphasized healthy dietary choices (eg, fruits and vegetables, whole grains, lean proteins), limiting added sugars, saturated fats, and sodium.^1-3

To monitor and reinforce adhering to the diet, participants attended in-person visits on weeks 2, 4, and 6, and were contacted either by phone or email on weeks 1, 3, 5, and 7. All participants returned for a final visit on week 8, with those in the IF group returning on the first fasting day to ensure comparability with baseline. All outcomes were assessed at weeks 0 (baseline) and 8, and evaluated brain health measures, cognition and physical activity, and systemic and peripheral metabolism measures.²

According to the findings, both diets had produced comparable benefits on neuron-derived extracellular vesicle biomarkers of neuronal IR, brain-age-gap estimate, and magnetic resonance spectroscopy glucose, demonstrating that these measures are sensitive indicators of the brain’s response to dietary interventions. Both diets were shown to improve peripheral metabolic indices—including weight, BMI, waist circumference, circulating lipids, and peripheral IR measures—with IF producing about a 2-times decrease in BMI, weight, and estimated mean daily calorie intake compared with HL. This superiority, however, did not extend into brain health outcomes except for cued recall and the executive function trend level. Alzheimer disease (AD) and AD-related dementia biomarkers in cerebrospinal fluid (CSF) and NDEVs did not change with either diet, according to the investigators.²

Further, executive function composite scores improved significantly for those on the IF diet, but not the HF diet. Based on assessments using the California Verbal Learning Test’s long-delay cued recall task, learning and memory had also improved significantly with the IF diet, whereas those on the HL diet demonstrated no effect. Sedentary bouts also decreased in the IF group and increased in the HL group. Across both groups, logical memory improved. In addition, levels of amyloid-beta 42 and phosphorylated-tau 181 did not change in CFS with either diet, despite decreased levels in brain aging measures.^1,2

Additionally, the investigators noted that adverse events (AEs) were minimal and both diets were well-tolerated. The most frequent AEs were gastrointestinal and occurred in participants assigned to the IF group. Three participants (15.0%) reported experiencing constipation and 2 (10.0%) reported loose stools, notably during the 2 restricted days. Further, 3 participants in the IF group (15.0%) and 2 (10.0%) in the HL group reported occasional headaches that were either self-remitting or subsided with common treatments.²

"Many people think that eating a healthy diet or following an IF regimen are good ways to stave off cognitive decline during aging, but our study actually provided supporting evidence," said Dimitrios Kapogiannis, MD, National Institute on Aging and the Johns Hopkins University School of Medicine, in a news release. “Our study lays the groundwork for larger clinical trials that will examine a variety of dietary interventions that will help people have good brain health and live healthier, longer lives.”¹

REFERENCES

1. Medpage Today. Intermittent Fasting May Improve Memory, Executive Function, Early Trial Suggests. News release. August 4, 2024. Accessed August 12, 2024. https://www.medpagetoday.com/meetingcoverage/aaic/111363?xid=nl_mpt_morningbreak2024-08-05&mh=6d2b5f4f91352444bdf817a9c17750bc&utm_source=Sailthru&utm_medium=email&utm_campaign=MorningBreak_080524&utm_term=NL_Gen_Int_Daily_News_Update_active

2. Kapogiannis D, Manolopoulos A, Mullins R, et al. Brain responses to intermittent fasting and the healthy living diet in older adults. Cell Metabolism. 2024;36(8):1668–1678.e5. doi:10.1016/j.cmet.2024.05.017

3. Intermittent Calorie Restriction, Insulin Resistance, and Biomarkers of Brain Function. ClinicalTrials.gov identifier: NCT02460783. Updated April 2, 2024. Accessed August 12, 2024. https://clinicaltrials.gov/study/NCT02460783