Modified Mediterranean ketogenic diet may improve brain health

Key takeaways:

• A modified Mediterranean ketogenic diet may reduce the risk for Alzheimer’s disease.
• Researchers said that the findings offer critical insight into how diet could improve brain health.

A modified Mediterranean ketogenic diet was associated with changes in a biological pathway linked to Alzheimer’s disease among older adults with mild cognitive impairment, according to study results published in Alzheimer’s and Dementia.

The ketogenic diet has emerged as a potential candidate for Alzheimer’s disease treatment because of its known protective effects for seizures and metabolic dysregulation, Amanda Hazel Dilmore, a PhD student in Rob Knight's lab at the University of California, San Diego, and colleagues wrote.

“The ketogenic diet is a candidate therapeutic for Alzheimer’s disease because of its ability to improve mitochondrial function and cerebral bioenergetics, enhance autophagy, and reduce oxidative stress,” they wrote. “It also reduces neuronal hyperexcitability and leads to improved amyloid and tau regulation, substantiating its potential use for cognitive impairment.”

Dilmore and colleagues added that gut microbiota are critical for ketogenic diet-mediated protection against seizures and modulation of bile acids — a major factor in cholesterol metabolism. Interest in those relationships, they wrote, was the catalyst for their analysis of gut microbiota and metabolites related to cognitive status after a ketogenic diet intervention compared with a low-fat-diet intervention.

“We hope that better understanding this complex relationship between diet, cognitive status and gut health will lead to new interventions to prevent and treat Alzheimer’s disease,” Suzanne Craft, PhD, professor of gerontology and geriatric medicine at Wake Forest University School of Medicine, said in a press release.

The researchers randomly assigned 20 prediabetic adults with either normal cognition or mild cognitive impairment (MCI) to a high-fat modified Mediterranean ketogenic diet (MMKD) or a low-fat American Heart Association diet for 6 weeks. After a 6-week washout period, the participants then began the alternate diet. To analyze changes in gut microbiome and metabolome, the researchers collected stool samples at five timepoints throughout the interventions.

Dilmore, Craft and colleagues found that, through modulation of GABA levels and gut-transit time, the MMKD may help older adults with MCI.

“Broadly, our investigation demonstrated that controlled changes in diet led to widespread changes in the microbiome and metabolome over time,” they wrote.

More specifically, the researchers found that those with MCI on the MMKD had lower levels of GABA — an inhibitory neurotransmitter — and GABA-producing microbes. They also had higher levels of GABA-regulating microbes. Notably, low levels of GABA have been linked to conditions like Alzheimer’s disease.

“Our study is the first to show that diet modulates GABA differently in MCI,” Craft said in the release.

The researchers also noted that those with MCI who also had curcumin in their diet had an altered bile acid pool and lower levels of bile salt hydrolase-containing microbes, which they wrote suggests reduced gut motility.

“Gut microbiota are known to modulate the bile acid pool; given that bile acids are the primary agent of cholesterol depletion in the brain, gut microbiota-induced changes to the bile acid pool may mitigate the dysregulation of cholesterol metabolism,” they wrote.

Dilmore, Craft and colleagues acknowledged that the study was limited because of its small sample size and “relatively brief intervention period,” but acknowledged the importance of their results.

“These findings provide crucial insight into how diet may affect the microbiome and improve brain health,” Craft said in the release. “Larger studies are needed to assess the role diet interventions play in patients with cognitive impairment.”

References:

• Dilmore AH, et al. Alzheimers Dement. 2023;doi:10.1002/alz.13007.
• Modified Mediterranean ketogenic diet may benefit adults at risk for Alzheimer's disease. https://www.eurekalert.org/news-releases/985220. Published April 5, 2023. Accessed April 6, 2023.