How food, exercise and GLP-1 drugs influence brain power
By Austin Perlmutter, MD
Brain Power: How Brain Energy Drives Brain Health
Brain metabolism is a fundamental aspect of overall brain health, playing a critical role in cognitive function, aging, and disease prevention. Unlike other organs, the brain requires a continuous and substantial supply of energy to function optimally. In fact, while it’s only about 2-3 lbs., the brain uses around 20-25% of the body’s energy. This energy typically comes from glucose (aka blood sugar), but under certain conditions, the brain can also utilize alternate fuel sources such as ketones and lactate. The interplay of these fuels is crucial for maintaining brain health, particularly in the context of aging and neurodegenerative diseases like Alzheimer’s. In this article, we explore how lifestyle factors such as exercise and diet, as well as emerging pharmacological interventions like GLP-1 related drugs, can influence brain metabolism.
Brain Metabolism, Alzheimer’s Disease, and Aging
Aging is associated with a decline in metabolic efficiency, and this is particularly evident in the brain. As we age, the brain’s ability to utilize glucose diminishes, leading to a state of energy deficit that can contribute to cognitive decline. This is one of the key factors underlying the development of Alzheimer’s disease, a neurodegenerative disorder characterized by progressive memory loss and cognitive impairment.
In Alzheimer’s disease, there is a significant reduction in glucose metabolism in the brain, a phenomenon known as “brain hypometabolism.” This is often detected years before clinical symptoms appear and is thought to contribute to the accumulation of amyloid-beta plaques and tau tangles, the pathological hallmarks of Alzheimer’s. Moreover, impaired glucose metabolism can exacerbate oxidative stress and inflammation, further accelerating neurodegeneration.
The use of alternate fuel sources, such as ketones, has shown promise in counteracting brain hypometabolism in Alzheimer’s patients. Ketogenic diets and exogenous ketone supplements are being explored as potential therapeutic strategies to provide the brain with an alternative energy source, thereby improving cognitive function and slowing disease progression.
The Role of Exercise in Brain Metabolism
Exercise is one of the most effective ways to enhance brain metabolism and promote cognitive health. Physical activity increases blood flow to the brain, improving the delivery of oxygen and glucose to neurons. It also stimulates the production of brain-derived neurotrophic factor (BDNF), a protein that supports the growth and survival of neurons and enhances synaptic plasticity, which is crucial for learning and memory.
Certain types of exercise, particularly aerobic exercise like running, swimming, and cycling, have been shown to be especially beneficial for brain metabolism. These activities increase the efficiency of mitochondrial function in neurons, enhancing the brain’s ability to produce and utilize energy. Resistance training, such as weightlifting, also contributes by improving insulin sensitivity, which can help maintain healthy glucose metabolism in the brain.
In one remarkable interventional study conducted in people who were overweight or obese, it was found that an 8-week intervention of aerobic exercise was sufficient to alter brain sensitivity to insulin. This powerful research suggests that exercise may directly act on brain metabolic state to improve our ability to use fuel.
The Influence of GLP-1 Related Drugs on Brain Metabolism
Glucagon-like peptide-1 (GLP-1) related drugs, such as Ozempic, originally developed for the treatment of type 2 diabetes, have gained attention for their potential effects on brain metabolism. GLP-1 is a hormone that enhances insulin secretion and promotes satiety, but it also has neuroprotective properties.
In the brain, GLP-1 receptors are expressed in regions involved in energy balance and cognition, such as the hippocampus and hypothalamus. Activation of these receptors by GLP-1 drugs can enhance glucose metabolism, reduce oxidative stress, and promote the survival of neurons. These effects are particularly relevant in the context of neurodegenerative diseases and cognitive decline.
Recent studies suggest that GLP-1 related drugs may help mitigate the metabolic deficits observed in Alzheimer’s disease by improving glucose utilization in the brain. Moreover, these drugs are linked to reduced inflammation and oxidative stress, both of which are key contributors to neurodegeneration. With this said, GLP-1 related drugs do come with side effect risks, as well as the potential for muscle loss. They also don’t address multiple brain pathways that can be better targeted using a holistic approach to brain health. Therefore, these medications should not be seen as a replacement for lifestyle modification when it comes to protecting brain health.
Diet and Brain Metabolism
A diet rich in whole foods, healthy fats, and low in refined sugars supports optimal brain function by providing a steady supply of energy and reducing inflammation. The ketogenic diet, in particular, has been shown to enhance ketone production, providing an alternative fuel source for the brain. While this type of diet may not generalize to most people (there are risks associated with long-term adherence to a more restrictive diet like the ketogenetic diet), it has shown some promise in particular regarding hypometabolic brain states like Alzheimer’s disease. In addition, it's notable that in preclinical (and some clinical) research, foods like olive oil, Tartary buckwheat fiber and protein may help to activate the body's natural production of GLP-1. Some of the core dietary considerations to support healthy brain metabolism include:
Consuming fiber-rich foods
Avoiding added sugars
Minimizing processed foods
Decrease refined carbohydrate intake
Conclusion
Understanding the intricacies of brain metabolism is key to promoting cognitive health and preventing neurodegenerative diseases like Alzheimer’s. the influence of lifestyle factors such as exercise and diet all contribute to maintaining a healthy brain. Emerging treatments, including GLP-1 related drugs, offer the potential for promising avenues for enhancing brain metabolism and protecting against cognitive decline, but shouldn’t be seen as a panacea, and can come with side effects. By adopting a holistic approach that integrates diet, exercise, and innovative therapies, we can support brain health throughout the aging process.
BONUS!
The Role of Alternate Fuel Sources: Ketones and Lactate
While glucose is the primary energy source for the brain, alternate fuel sources like ketones and lactate play a significant role, especially during periods of glucose scarcity or metabolic stress. Ketones, produced during the breakdown of fats, can cross the blood-brain barrier and serve as an efficient fuel for neurons. This is particularly important during prolonged fasting, ketogenic diets, or in states of insulin resistance where glucose utilization is impaired.
Lactate, traditionally viewed as a metabolic waste product, has recently gained recognition as a valuable energy substrate for the brain. Produced by astrocytes, lactate can be shuttled to neurons where it is converted into pyruvate and used in the mitochondrial Krebs cycle to produce ATP, the energy currency of the cell. This lactate shuttle is especially crucial during intense neuronal activity when the demand for energy exceeds the supply of glucose.
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