Keto Diet Benefits For Dementia Patients: Does It Work?

Dementia is a growing issue, with the number of people living with the condition predicted to rise from 55 million in 2020 to 139 million by 2050. Alzheimer's Disease is the most common form of dementia, accounting for 60-80% of cases. While treatments can slow the progression of the disease, none can stop it. Scientists are therefore testing a range of interventions, including the keto diet – a high-fat, very low-carbohydrate diet. This article will explore the evidence for and against the keto diet as a treatment for dementia.

Ketogenic diet and brain function

The ketogenic diet is a high-fat, low-carbohydrate diet with moderate amounts of protein. The brain usually runs on glucose, a critical source of energy, but in people with Alzheimer's, the brain's ability to use glucose for fuel is decreased. This is known as brain insulin resistance. The ketogenic diet has been found to be effective in helping people with type 2 diabetes get better control over their blood sugar levels. On a keto diet, when the body runs out of carbs as fuel, the liver burns fat for energy instead, producing ketones, which serve as a backup energy source.

The brain in people with Alzheimer's can still use ketones for energy. The theory is that if the brain receives ketones as energy instead of glucose, it might help restore some cognitive function. A study published in 2021 recruited 26 people with an Alzheimer's diagnosis. The scientists compared a ketogenic diet with the participants' regular diet as a control. They found that when people followed the keto diet, they reported improvements in daily function and quality of life compared with when they followed their usual diets.

The ketogenic diet has also been found to reduce inflammation, which is associated with dementia. This provides another way in which the keto diet might help slow down dementia. However, there are some drawbacks and limitations to the keto diet. It can be tough to stick to long-term, and it may also lead to cardiovascular problems, GI effects, an increased risk of pancreatitis, fatty liver disease, renal calculi, and osteoporosis.

Another way to induce ketogenesis is through fasting or caloric restriction. This has been shown to improve longevity and reduce the risk of chronic disease and has similar positive effects on aging brains. A conventional healthy diet with mild caloric restriction could be a more sustainable way to improve brain function without the health risks of an extreme or extended version of the ketogenic diet.

Ketones as an alternative energy source

The brain typically relies on glucose as its primary energy source. However, in people with Alzheimer's disease, the brain's ability to utilise glucose for fuel is impaired. This is known as brain insulin resistance and is akin to type 3 diabetes.

Ketones, produced by the liver, offer an alternative energy source for the brain. When the body has no glucose fuel, either due to fasting or a low/zero-carbohydrate diet, the liver converts fat into ketones, which can be used by the brain for energy. This process is called ketogenesis and can be triggered by a ketogenic diet or caloric restriction, such as intermittent fasting.

The ketogenic diet is a high-fat, very low-carbohydrate diet, which has been used to successfully treat epilepsy for over 100 years. More recently, it has been shown to help people with type 2 diabetes better manage their blood sugar levels.

In Alzheimer's patients, the brain's utilisation of glucose is decreased, and ketones can step in as an alternative fuel source. The brain can still use ketones for energy, potentially improving cognition and restoring some cognitive function.

A small pilot study by the KU Alzheimer's Disease Research Center found that the ketogenic diet improved cognitive test scores in people with Alzheimer's disease after three months. The average increase in scores was higher than that associated with some existing memory medications.

Additionally, the ketogenic diet has been found to reduce inflammation, which is also beneficial for the brain. Inflammation tends to increase with age and is associated with dementia. The anti-inflammatory effects of the keto diet may help slow dementia progression.

While the ketogenic diet shows promise in delaying or mitigating symptoms of cognitive decline, it is not without its drawbacks. Adherence can be challenging, and long-term adherence may lead to cardiovascular problems, gastrointestinal issues, increased risk of pancreatitis, fatty liver, renal calculi, and osteoporosis.

Caloric restriction, such as intermittent fasting, may be a more sustainable approach to inducing ketogenesis and improving brain function without the risks associated with the extreme or extended ketogenic diet.

The impact of ketogenic diet on inflammation

The Impact of the Ketogenic Diet on Inflammation

The ketogenic diet has been shown to have anti-inflammatory effects, which may be beneficial in the treatment of dementia. Inflammation is a key factor in the neuropathology of Alzheimer's disease, and it is associated with neurotoxic mechanisms that lead to neuronal loss in the brain regions responsible for memory and cognitive processes.

The ketogenic diet may reduce inflammation by inhibiting the activation of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB). This results in the downregulation of COX2 and inducible nitric oxide synthase expression, which are associated with increased immune response. Additionally, the activity of cytokines, such as IL-1b, IL-6, CCL2/MCP-1, and TNF-α, is diminished.

The ketogenic diet also influences the anti-inflammatory action via activation of microglial cells, pro-apoptotic properties, and elevated concentrations of neuroprotective mediators, including neurotrophins and molecular chaperones.

Another mechanism by which the ketogenic diet may reduce inflammation is through the inhibition of histone deacetylases (HDACs), which play a role in altering chromatin structure and accessibility. β-hydroxybutyrate (β-OHB), a ketone body produced during the ketogenic diet, inhibits HDACs 1, 3, and 4 (class I and IIa) in vitro, leading to improved memory function and synaptic plasticity.

Furthermore, ketone bodies can inhibit the NOD-like receptor 3 inflammasome (NLRP3), which controls the activation of caspase-1 and the release of pro-inflammatory cytokines, such as IL-1β and IL-18.

Overall, the anti-inflammatory effects of the ketogenic diet may contribute to its potential benefits in the treatment of dementia, particularly Alzheimer's disease.

The link between diet and cognitive decline

The keto diet works by reducing the body's reliance on glucose as its primary source of energy. When carb intake is minimal, the liver burns fat for energy instead, producing ketones, which can also be used as fuel by the brain. This process may be particularly beneficial for individuals with Alzheimer's disease, as their brains have reduced ability to use glucose efficiently, a condition known as "brain insulin resistance" or "type 3 diabetes". By providing the brain with an alternative energy source, the keto diet may help restore some cognitive function.

Evidence for the keto diet in dementia treatment

While the keto diet has been used successfully to treat epilepsy for over a century, its potential benefits for dementia are only recently being explored. Small-scale studies have shown encouraging results, with improvements in daily function, quality of life, and cognitive test scores reported by participants following the keto diet. However, these studies have been limited in size and duration, and more research is needed to confirm the effectiveness of the keto diet in treating dementia.

The link between inflammation and cognitive decline

In addition to improving glucose control, the keto diet has also been found to reduce inflammation, which is associated with dementia. As levels of inflammation tend to increase with age, this anti-inflammatory effect may be another way in which the keto diet could help slow the progression of dementia.

Alternative dietary approaches

While the keto diet has shown promise, it is not without its drawbacks. Adherence to the diet can be difficult, and it may not be a healthy long-term option for everyone. An alternative approach is to combine the keto diet with the Mediterranean diet, which emphasizes whole grains, olive oil, fish, fruits, and legumes. This combination has been linked to improved cognitive function and reduced risk of Alzheimer's disease in preliminary studies. Additionally, the MIND diet (Mediterranean-DASH Diet Intervention for Neurodegenerative Delay), which is similar to the Mediterranean keto diet, has also been associated with a reduced risk of Alzheimer's disease.

In conclusion, while the keto diet may not be a cure for dementia, it is a promising idea worth pursuing. Dietary interventions have the potential to play a significant role in slowing cognitive decline and improving the lives of individuals with dementia. However, more research is needed to fully understand the complex relationship between diet and cognitive decline.

The role of ketogenic diet in regulating GABA

The ketogenic diet has been used as a treatment for epilepsy since the 1920s. Although the mechanism by which the diet protects against seizures is unknown, there is evidence that it causes effects on intermediary metabolism that influence the dynamics of the major inhibitory and excitatory neurotransmitter systems in the brain.

Glutamate is the major excitatory neurotransmitter in the brain, while GABA (gamma-aminobutyric acid) is the major inhibitory neurotransmitter. The brain must continually synthesise and deliver to neurons the glutamate that they release upon depolarisation. It is also important that the brain rapidly and efficiently removes glutamate from the synaptic space to maintain low levels of glutamate in the synapse, maximising the signal-to-noise ratio upon release of this transmitter from nerve endings.

Astrocytes, a type of glial cell, are responsible for removing glutamate from the synapse, converting it to glutamine via the enzyme glutamine synthetase, and then exporting glutamine back to neurons. This process is known as the glutamate-glutamine cycle.

The ketogenic diet has been found to intensify the flux through the astrocytic glutamine synthetase pathway, providing more glutamine to serve as a precursor to GABA. In addition, the diet may alter neuronal handling of glutamate at nerve endings, making more glutamate available for the glutamate decarboxylase reaction in nerve endings, which is responsible for the synthesis of GABA.

In summary, the ketogenic diet appears to increase the synthesis of GABA in the brain by enhancing the conversion of glutamate to glutamine in astrocytes and providing more glutamine as a precursor for GABA synthesis in neurons.

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