Scientists from Wake Forest School of Medicine have found that a modified Mediterranean–ketogenic diet may help reduce the risk of Alzheimer’s disease by positively affecting the gut microbiome.
The research, led by Ravinder Nagpal and published in EBioMedicine, suggests that dietary changes can influence the balance of gut bacteria and related brain health markers.
Alzheimer’s disease is the most common cause of dementia, a condition marked by a progressive decline in memory, thinking, behaviour, and the ability to carry out everyday activities independently.
Growing evidence suggests that the gut microbiome — the trillions of bacteria, fungi, and other microorganisms living in the digestive tract — may play an important role in the development and progression of Alzheimer’s disease.
The gut microbiome is essential for overall health. It helps regulate digestion, supports the immune system, produces important metabolites, and even communicates with the brain through what is known as the gut–brain axis.
Some gut microbes can produce substances that influence inflammation and brain function, which may either protect against or contribute to neurodegenerative diseases like Alzheimer’s.
In this study, researchers examined how the gut microbiome differed between older adults with mild cognitive impairment (MCI) and those with normal cognitive function.
Mild cognitive impairment is an early stage of cognitive decline, in which individuals experience noticeable memory problems but are still able to carry out most daily activities independently.
The team also wanted to know whether a modified Mediterranean–ketogenic diet could alter the gut microbiome in ways that were linked to changes in Alzheimer’s-related markers found in cerebrospinal fluid (CSF).
What is a Mediterranean–ketogenic diet?
The Mediterranean diet focuses on plant-based foods such as fruits, vegetables, legumes, whole grains, nuts, seeds, and extra virgin olive oil, along with moderate amounts of fish, seafood, poultry, eggs, and dairy.
The ketogenic diet, commonly used in medical settings to treat severe epilepsy in children, is high in fat, moderate in protein, and very low in carbohydrates. This eating pattern forces the body to switch from burning carbohydrates to burning fat, producing molecules called ketones that can be used as an alternative energy source for the brain.
The modified Mediterranean–ketogenic diet used in this study combined elements of both approaches, aiming to deliver the brain-health benefits of Mediterranean foods while promoting the fat-burning state associated with ketosis.
The study involved 17 older adults, including 11 with mild cognitive impairment and 6 who were cognitively normal. Participants followed either the modified Mediterranean–ketogenic diet or the American Heart Association (AHA) diet for six weeks.
Researchers analysed participants’ gut microbiome and Alzheimer’s disease biomarkers in cerebrospinal fluid both before and after the diet intervention.
Key findings
Before the dietary changes, there were no major differences in the overall diversity of gut bacteria between people with normal cognition and those with mild cognitive impairment. However, people with MCI showed unique patterns of certain microbial species, suggesting a possible microbial “signature” linked to early cognitive decline.
The two diets also affected gut bacteria differently:
- The modified Mediterranean–ketogenic diet slightly reduced levels of lactate and acetate while increasing propionate and butyrate — short-chain fatty acids that are thought to support gut and brain health.
- In contrast, the American Heart Association diet increased acetate and propionate, but reduced butyrate, a compound known for its anti-inflammatory and neuroprotective properties.
These shifts in gut metabolites suggest that specific dietary patterns may create an intestinal environment that is more or less favourable for brain health.
The findings support the idea that certain microbial patterns may be associated with mild cognitive impairment and that changing the diet can influence these patterns in potentially beneficial ways. By altering the gut microbiome and its metabolites, a modified Mediterranean–ketogenic diet may help reduce biological risk factors linked to Alzheimer’s disease.
While further research on larger populations is still needed, this study adds to a growing body of evidence that diet — particularly diets that support both metabolic and gut health — may be a powerful, non-invasive strategy for protecting brain function as we age.
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