ISLAMABAD, MARCH 27 (ONLINE): A ketogenic (keto) diet can slow the arrival of the mild cognitive loss that signals the development of Alzheimer’s disease, a new study in mice suggests.
The authors of the study found that a low-carb, high-fat keto diet results in an increase in BHB molecules that have been associated with protection against neuroinflammation.
Experts have expressed a need for confirmatory support in humans, particularly since “Alzheimer’s disease” in mice does not fully replicate the human version.
In a new study using a mouse model, a ketogenic (keto) diet postponed the onset of Alzheimer’s disease (AD).
Delaying Alzheimer’s is being credited with a sevenfold increase in the mice’s levels of the beta-hydroxybutyrate (BHB) molecule.
The BHB molecule has been associated with delays in the onset of mild cognitive dementia typical of the early stages of Alzheimer’s. The moleculeTrusted Source is also found in humans, where it’s produced when the body burns fat for energy in order to feed the body’s mitochondriaTrusted Source. The molecule supports the transfer of energy from the liver to the rest of the body when glucose levels are insufficient.
The authors of the study from the University of California, Davis (UC Davis) have previously published researchTrusted Source finding that BHB, depending on dosage, is anti-inflammatory for human brain cells inflamed by beta-amyloid plaques.
These plaques were, for a time, considered the main cause of Alzheimer’s. Yet, many people have the plaques who never develop Alzheimer’s, and foundational research that identified them as an Alzheimer’s cause has since been discredited.
The new study involved genetically modified APP/PS1 mice who express a mouse/human amyloid precursor protein as well as a mutant human presenilin 1 gene. Both target central nervous system neurons.
The mice were bred at UC Davis. Their female and male offspring lived in a 12-hour light and 12-hour dark environment, with up to four mice in a cage eating a standard mouse chow diet for six months. At that age, they were assigned to weight-balanced groups, with each mouse living in a separate enclosure for the remainder of the study, so researchers could control their consumption of food.
Mice were given either a keto diet or a carbohydrate-rich standard diet — both diets provided the same number of calories.
The researchers observed that female mice had higher levels of BHB in their bodies than males, as well as brain enzymes known to support memory.
At the same time, male mice who were switched to a late-midlife keto diet exhibited improved spatial memory.
The study is published in Nature Communications Biology.Trusted Source
How keto affects neuroinflammation
Michelle Routhenstein, registered dietician and nutritionist at EntirelyNourished.com, who was not involved in the study, explained that “A ketogenic diet is a high fat, low-carbohydrate eating approach that causes ketosis.”
“Ketosis is a metabolic state where the body primarily burns fat for fuel instead of carbohydrates, which yields ketone bodies as an alternative energy source,” she continued.
One concern regarding the higher levels of fat in a keto diet is the promotion of neuroinflammation that can adversely affect cognitive health. However, more of the right fats can reduce neuroinflammation.
Indeed, in the study, lead author Dr. Gino A. Cortopassi told Medical News Today that “When the exact same number of calories are delivered by keto as by the control diet, there is a significant reduction of systemic inflammatory cytokinesTrusted Source.”
“There are neuroprotective elements found in certain fats, like omega-3 fatty acids, fat-soluble carotenoids, and vitamins, which can help combat inflammation and oxidative stress,” Routhenstein noted.
On the other hand, Routhenstein said, “While some fat in the diet is helpful to reduce inflammation and neuroinflammation, excessive intake of saturated fats could potentially elevate cholesterol levels and cardiovascular risk.”
“Long-term adherence [to a keto diet] may also lead to nutrient deficiencies and adverse effects on heart and gut health, necessitating careful monitoring and balanced nutrition to mitigate potential harms.”
— Michelle Routhenstein
As a cardiovascular dietician, Routhenstein does not recommend a strict keto diet.
How to raise BHB levels
Dr. Cortopassi explained how BHB levels increase in humans, saying “After humans have fasted for about 12 hours, BHB levels rise. This is because the carbohydrate stores have become exhausted.”
He added that humans on a keto diet have significantly higher levels of BHB than humans on a standard, carb-rich, diet.
Dr. Cortopassi said human BHB levels may be increased in any of three ways.
First, obviously, is going on a keto diet. Second, one may take a BHB supplement. Third, and least effective, he said, is putting oneself on a one-meal-a-day carbohydrate diet — in which BHB levels will slowly rise after the liver’s glycogen is depleted. However, BHB levels will drop “precipitously” when the next carbohydrate meal is consumed.
Before making any significant dietary changes, it is best to consult your physician.
Mouse versus human studies of Alzheimer’s
“It is very important to recognize that this was a study in mice and does not provide any conclusive evidence of ketogenic diet and Alzheimer’s progression in humans,” said Routhenstein.
Dr. Stefania Forner, Ph.D., Alzheimer’s Association director of medical and scientific relations, who was also not involved in the study, agreed.
“This study is based on research in a mouse model of Alzheimer’s. While animal models of the disease are somewhat similar to how Alzheimer’s progresses in humans, they do not replicate the disease in humans exactly. Models are important in helping us understand the basic biology of the disease, but we need human studies in representative populations for ideas to be fully validated.”
— Dr. Stefania Forner
While the new study presents “intriguing” findings, Dr. Forner felt “more research is needed to understand the impacts and outcomes of a ketogenic diet on people living with, or at risk for, Alzheimer’s.”
Dr. Forner made clear, however, that, “At this point, no one should adopt this diet to prevent or treat Alzheimer’s or other cognitive impairment. If you are considering changing your diet for this purpose, always talk to your healthcare provider first.”
In 2025, the Alzheimer’s Association expects to publish the results of their U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (U.S. POINTER). This is a two-year clinical trial involving a large representative group of Americans.
Dr. Forner said it is investigating whether “lifestyle interventions that simultaneously target many risk factors — including diet — can protect cognitive function in older adults who are at increased risk for cognitive decline.”
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