Focus areas

RESEARCH FOCUS AREAS

At LBI, we investigate the interaction between lifestyle and the brain in health and disease across lifespan, focusing on three main domains:

COGNITIVE PERFORMANCE

METABOLIC PSYCHIATRY

HEALTHY AGING

Human Brain and Nutrition

In the evolutionary journey of our species, nutrition played a pivotal role, and this is especially true for the development of our brain.

A large brain comes with obvious benefits like complex reasoning skills, planning, or language skills. These cognitive features distinguish humans from the rest of the animal kingdom. However, large brains also represent an energetic challenge: the human brain accounts for 20-25% of the resting metabolic rate.

To support the large and energy-costly brain, our whole body and diet had to change. Compared to other primates, humans are relatively under-muscled (which saves energy) and over-fat (which enables us to store more energy). Also, our diet is very energy-dense. We only eat quite a small volume of food which is rich in calories.

These anatomical and dietary changes helped us to support the high-energy demands of our brain. Another important evolutionary adaptation to the high-energy demands of our brain is the ability to switch between its two primary fuels – glucose and ketones.

Ketosis

Being ‘in ketosis’ simply means having a certain amount of ketones (specific biochemical molecules) in your blood. Attaining a physiological state of ketosis is marked by blood ketone levels above 0.5 mMol/L.

When following a typical Western diet, rich in carbohydrates and eating all day long, glucose is readily available and serves as the primary energy source for the brain. In this situation, there will be limited to no ketones circulating in your blood. When intake of carbohydrates is restricted, the body undergoes a so-called metabolic shift, transitioning from reliance on glucose to utilizing ketones.

The metabolic shift can be induced by fasting (obstructing from food for a certain amount of time), or following a ketogenic diet, characterized by high fat, adequate protein, and low carbohydrate intake. In these situations, the liver will transfer fat (more specifically fatty acids) into ketones. One can also boost blood ketone levels by taking nutritional supplements (such as exogenous ketones or MCT oil).

Ketones traverse the blood-brain barrier, providing an energy source for the brain. Therefore, ketosis is an essential metabolic adaptation to periods of low carbohydrate availability. Without ketosis, our brains would run out of fuel in a couple of days. Thanks to ketosis, healthy people can survive several weeks without access to food. For most of human evolution, access to nutritional resources fluctuated over time. Therefore, it was common to be in ketosis. In our current environment, with high accessibility of high-carb food, entering ketosis is much less common.

Apart from serving as a potent brain fuel source, ketones also demonstrated anti-inflammatory and antioxidant properties conferring neuroprotective benefits.

Metabolic psychiatry

According to the World Health Organization, more than 1 in 8 people worldwide live with a mental disorder, and so far, conventional treatment options are falling short in effectiveness, necessitating the exploration of new approaches.

Metabolic psychiatry can be this new approach. This newly emerging field focuses on the interplay between the body and the brain, connecting metabolic dysfunction in the body with metabolic dysfunction in the brain and psychiatric illnesses. Complex biochemical pathways fuel the body and the brain and sustain overall well-being. If there is a hiccup anywhere in this system, it will have negative consequences on our mental and physical health.

Viewing mental disorders from a metabolic perspective is a drastic paradigm shift in our understanding and potential treatment of psychiatric disorders. So far, these disorders have been treated using behavioral and pharmacological approaches, focusing on symptom treatment rather than the underlying causes and commonly cause diverse side effects, many of which are metabolic. Therefore, investigating metabolic pathways in psychiatric disorders can provide a groundbreaking holistic understanding of lifestyle-brain interactions.

Given the complexity of psychiatric disorders as represented by the diversity of displayed symptoms of individuals with the same diagnosis, the need to tackle underlying mechanisms rather than simply treating separate symptoms arises. Metabolic psychiatry offers a promising route for more effective and personalizable treatments compared to traditional pharmacological treatment. By unraveling the metabolic underpinnings, personalized treatment strategies tailored to an individual's unique metabolic profile can be developed, introducing a new era of mental health care.

Using metabolic interventions, such as the ketogenic diet, we intend to modulate dysfunctional and/or disrupted metabolic pathways and, consequently, alleviate the broad spectrum of symptoms of psychiatric disorders long term. This is the core of metabolic psychiatry.

LBI’s own research currently focuses on autism spectrum disorder (ASD), and attention deficit hyperactivity disorder (ADHD), and post traumatic stress disorder (PTSD); while our communication and policy shaping efforts cover the whole metabolic psychiatry field.

Healthy ageing

Diseases responsible for the majority of deaths in developed countries, such as cardiovascular disease, cancer, type 2 diabetes, or dementia, have one thing in common – the risk of developing all of these diseases rises sharply with age.

For a long time, researchers considered ageing to be a non-modifiable risk factor - a process that can not be manipulated. The relatively new field of ageing science aims to change that. Scientists try to identify which molecular processes are responsible for ageing and whether these processes can be slowed down or maybe even reversed!

Calorie restriction is known to prolong the lifespan of many model organisms, and it decreases the risk of major diseases in humans. A growing body of scientific evidence also shows that calorie restriction positively affects “hallmarks of aging”, molecular processes implicated in the process of aging.

As ketosis accompanies calorie restriction or fasting, it is hypothesized that ketones themselves might be responsible for some of the benefits of calorie restriction and might alleviate some of the age-related physiological dysfunctions.

One of our key research areas is metabolic treatment to prevent age-related cognitive decline. Building on strong published pilot studies and some larger trials, we are conducting studies using metabolic lifestyle interventions in mild cognitive impairment patients. The goal is to prevent Alzheimer’s development as part of a broader aim to promote healthy ageing.

Disclaimer
The content of this website is provided by the Lifestyle Brain Interaction research group. It does not necessarily represent the views, strategy, or policies of Leiden University.