An intermittent fasting (IF) diet and a standard healthy living (HL) diet focused on healthy foods both lead to weight loss, reduced insulin resistance (IR), and slowed brain aging in older overweight adults with IR, new research showed. However, neither diet has an effect on Alzheimer’s disease (AD) biomarkers.
Although investigators found both diets were beneficial, some outcomes were more robust with the IF diet.
“The study provides a blueprint for assessing brain effects of dietary interventions and motivates further research on intermittent fasting and continuous diets for brain health optimization,” investigators led by Dimitrios Kapogiannis, MD, chief, human neuroscience section, National Institute on Aging, and adjunct associate professor of neurology, The Johns Hopkins University School of Medicine, wrote.
The findings were published online on June 19 in Cell Metabolism.
Cognitive Outcomes
The prevalence of IR — reduced cellular sensitivity to insulin that’s a hallmark of type 2 diabetes — increases with age and obesity adding to an increased risk for accelerated brain aging as well as AD and related dementias (ADRD) in older adults who have overweight.
Studies reported healthy diets promote overall health, but it’s unclear whether, and to what extent, they improve brain health beyond general health enhancement.
Researchers used multiple brain and cognitive measures to assess dietary effects on brain health, including peripherally harvested neuron-derived extracellular vesicles (NDEVs) to probe neuronal insulin signaling; MRI to investigate the pace of brain aging; magnetic resonance spectroscopy (MRS) to measure brain glucose, metabolites, and neurotransmitters; and NDEVs and cerebrospinal fluid to derive biomarkers for AD/ADRD.
The study included 40 cognitively intact overweight participants with IR, mean age 63.2 years, 60% women, and 62.5% Caucasian. Their mean body weight was 97.1 kg and mean body mass index (BMI) was 34.4 kg/m2.
Participants were randomly assigned to 8 weeks of an IF diet or a HL diet that emphasizes fruits, vegetables, whole grains, lean proteins, and low-fat dairy and limits added sugars, saturated fats, and sodium.
The IF diet involved following the HL diet for 5 days per week and restricting calories to a quarter of the recommended daily intake for 2 consecutive days.
Both diets reduced neuronal IR and had comparable effects in improving insulin signaling biomarkers in NDEVs, reducing brain glucose on MRS, and improving blood biomarkers of carbohydrate and lipid metabolism.
Using MRI, researchers also assessed brain age, an indication of whether the brain appears older or younger than an individual’s chronological age. There was a decrease of 2.63 years with the IF diet (P=.05) and 2.42 years with the HL diet (P <.001 in the anterior cingulate and ventromedial prefrontal cortex.>
Both diets improved executive function and memory, with those following the IF diet benefiting more in strategic planning, switching between two cognitively demanding tasks, cued recall, and other areas.
Hypothesis-Generating Research
AD biomarkers including amyloid beta 42 (Aβ42), Aβ40, and plasma phosphorylated-tau181 did not change with either diet, a finding that investigators speculated may be due to the short duration of the study. Light-chain neurofilaments increased across groups with no differences between the diets.
In other findings, BMI decreased by 1.41 kg/m2 with the IF diet and by 0.80 kg/m2 with the HL diet, and a similar pattern was observed for weight. Waist circumference decreased in both groups with no significant differences between diets.
An exploratory analysis showed executive function improved with the IF diet but not with the HL diet in women, whereas it improved with both diets in men. BMI and apolipoprotein E and SLC16A7 genotypes also modulated diet effects.
Both diets were well tolerated. The most frequent adverse events were gastrointestinal and occurred only with the IF diet.
The authors noted the findings are preliminary and results are hypothesis generating. Study limitations included the study’s short duration and its power to detect anything other than large to moderate effect size changes and differences between the diets. Researchers also didn’t acquire data on dietary intake, so lapses in adherence can’t be excluded. However, the large decreases in BMI, weight, and waist circumference with both diets indicated high adherence.
The study was supported by the National Institutes of Health’s National Institute on Aging. The authors reported no competing interests.
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