Alzheimer`s Disease(AD), is a neurodegenerative disease characterized by progressive cognitive impairment and memory impairment, the global prevalence of dementia has been estimated to be as high as 24 million. As the population worldwide continues to age, the number of individuals at risk will also increase and is predicted to double every 20 years until at least 2040. Some experts say that more than half of the elderly over 80 will show cognitive impairment. Current therapies can only temporarily relieve symptoms and cannot delay or reverse the course (1) (2).

The etiology of Alzheimer disease remains unclear, the well accepted hypothesis is Beta amyloid deposition hypothesis currently. But with the failure of clinical trials of multiple anti-ß amyloid deposition drugs, this hypothesis has faced to be more questioned and challenged. The bioenergy hypothesis becomes a study hotspot in the pathogenesis of Alzheimer’s disease.

 What is bioenergy hypothesis?

The bioenergy hypothesis states that glucose metabolism disorders in certain areas of the brain may being 20 years prior to the onset of clinical symptoms in Alzheimer’s disease. Insufficient energy intake will induce oxidative stress and neuroinflammation, which lead to brain dysfunction. Meanwhile, glucose intake in certain regions of the brain of healthy elder people will also decrease compared to younger populations (13), which can also explain the decline in cognitive function during normal aging.

A study led by Madhav Thambisetty (NIA) found distinct abnormalities in glycolysis, the main process by which the brain breaks down glucose, with evidence linking the severity of the abnormalities to the severity of Alzheimer’s pathology. Researchers believed that reduced glycolysis in the brain may be related to the occurrence of Alzheimer’s disease symptoms such as memory problems and cognitive decline (3) (5). More and more studies have confirmed that in Alzheimer’s disease (AD), the brain’s absorption and metabolism of glucose deteriorates.

Studies have confirmed that both the brain’s absorption and metabolism of glucose deteriorated in Alzheimer’s disease. Compared to age‐matched, cognitively normal controls, there is a particular pattern of glucose hypometabolism in the parietal and temporal cortices, where the glucose deficit rate is 20–25%(4) (6).

Now, multiple PET studies have found that patients with AD inheritance or lifestyle have abnormally intake and metabolic rates for glucose (CMRg) in brain before cognitive symptoms appear (7) (8) (9) (10) (11) (12).These findings suggest that disorders of glucose metabolism in certain brain regions (temporal cortex, parietal cortex, posterior cingulate cortex, etc.) are early pathological features of Alzheimer’s disease. Reduced brain glucose metabolism in AD patients can occur long before AD symptoms appear (about 20 years), and decreased glucose uptake may contribute to related cognitive decline.

The now classic studies by Owen et al. and Drenick et al. demonstrated that ketones are the main reserve fuel for the brain.(14)(15)  Studies indicated that there were no significantly different in the brain ketone uptake between AD and controls. Hence, providing the aging brain with more ketones may help it overcome the creeping deficit in glucose uptake and metabolism, thereby delaying brain energy exhaustion and decreasing the risk of AD. (3)

Some MCTs-based products are now available in the US and European markets. It has been reported that taking single-dose (16) mild or moderate AD or taking MCTs regularly for several months (17) can improve cognitive function, which greatly promoted the advent of these products.

Clinical studies proved that adding MCT in daily diet can improve cognition

A follow-up randomized controlled trial evaluated the effectiveness of the cognitive ability of 140 patients with Alzheimer’s disease after taking 20 grams of MCT daily for 90 days. After 45 days, the improvement in ADAS-cog was significantly greater in the MCT group than in the placebo group, and it was almost significant (p = 0.077) after 90 days.(17)(18) Data from clinical trials suggest that MCTs improve cognition in patients with mild to moderate AD in apolipoprotein E4-negative patients.

A Japanese study showed that in a long-term MCT (20 g MCT / day) trial, 16 of 20 patients completed a 12-week regimen. The chronic consumption of the ketogenic formula was therefore suggested to have positive effects on verbal memory and processing speed in patients with AD (19).

These studies show that MCT supplements can improve cognitive function, and that in elderly people with mild to moderate cognitive impairment and APOE4-negative, cognitive function can be enhanced after taking 20 grams daily for 90 days.

A study on non-dementia elderly showed that taking 20 grams of ketogenic formula with MCT daily could enhance memory storage, visual memory, and task switching ability of non-demented elderly (20).

Another study in diabetes patients showed that ApoE-negative patients with mild to moderate cognitive impairment improved cognitive function by taking MCT 20 grams daily for three months (21).

Summary: The bioenergy hypothesis believes that Alzheimer’s disease is caused by impaired glucose metabolism in a certain region of the brain, resulting in insufficient brain energy and neurological inflammation. By supplementing MCT or ketone bodies in the daily diet early (at the age of 40), the brain can make up for the energy gap caused by the decline in glucose metabolism, which may prevent or delay the decline of brain cognitive function and reduce the risk of developing dementia.

Reference：

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