"Creatine is very crucial for energy-consuming cells in skeletal muscle throughout the body, but also in the brain and in the heart," said Chin-Yi Chen, a research scientist at Virginia Tech's Fralin Biomedical Research Institute at VTC.

Chen is part of a research team working to develop a technique that uses focused ultrasound to deliver creatine directly to the brain. The work, being conducted in the lab of Fralin Biomedical Research Institute Assistant Professor Cheng-Chia "Fred" Wu, will be supported by a $30,000 grant from the Association for Creatine Deficiencies.

Creatine plays a vital role in the brain, where it interacts with phosphoric acid to help create adenosine triphosphate, a molecule essential for energy production in living cells. In addition to its role in energy production, creatine also influences neurotransmitter systems.

For example, creatine influences the brain's major inhibitory pathways that use the neurotransmitter gamma-aminobutyric acid, which limits neuronal excitability in the central nervous system. It may play a role in a variety of functions, including seizure control, learning, memory, and brain development.

A growing body of research suggests that creatine may itself function as neurotransmitter, as it is delivered to neurons from glial cells in the brain and can influence signaling processes between other neurons. While creatine deficiency disorders can weaken the skeletal muscle and the heart, they can also severely affect the brain. Many patients see increased muscle mass and body weight with creatine supplements, but they often continue to face neurodevelopmental challenges that can hinder their ability to speak, read, or write.

This is largely caused by the brain's protective blood-brain barrier. This selective shield blocks harmful substances like toxins and pathogens from entering brain tissue, but it can also prevent beneficial compounds like creatine from reaching the brain when levels are low.

Wu studies therapeutic focused ultrasound, which precisely directs sound waves to areas of the brain to which access has been opened temporarily. The process allows drugs to reach diseased tissue without harming surrounding healthy cells. While Wu is investigating this method as a potential treatment for pediatric brain cancer, he also sees potential in applying it to creatine deficiency.

"Through the partnership between Virginia Tech and Children's National Hospital, I was able to present our work in focused ultrasound at the Children's National Research & Innovation Campus," Wu said. "There, I met Dr. Seth Berger, a medical geneticist, who introduced me to creatine transporter deficiency. Together, we saw the promise that focused ultrasound had to offer."

The Focused Ultrasound Foundation has recognized Virginia Tech and Children's National as Centers of Excellence. Wu said the two organizations bring together clinical specialists, trial experts, and research scientists who can design experiments that could inform future clinical trials.

"It was a moment that made me really excited -- that I had found a lab where I could move from basic research to something that could help patients," Chen said. "When Fred asked me, 'Are you interested in this project?' I said, 'Yes, of course.'"

Because creatine deficiencies can impair brain development, the early stages of Chen's project will concentrate on using focused ultrasound to deliver creatine across the blood-brain barrier. Chen hopes the technique will restore normal brain mass in models of creatine deficiency.

Dr Juan Franco and colleagues say, on average, people with high weight will not be able to sustain a clinically relevant weight loss with lifestyle interventions, while the potential harms of weight loss interventions, including the reinforcement of weight stigma, are still unclear.

They stress that a healthy lifestyle has important benefits, but that weight alone might not give an adequate picture of someone's health, and say doctors should provide high quality, evidence based care reflecting individual preferences and needs, regardless of weight.

Lifestyle interventions that focus on restricting an individual's energy intake and increasing their physical activity levels have for many decades been the mainstay recommendation to reduce weight in people with obesity, explain the authors.

However, rigorous evidence has indicated that these lifestyle interventions are largely ineffective in providing sustained long term weight loss and reducing cardiovascular events (eg, heart attacks and strokes) or death.

Even though a healthy lifestyle provides important benefits, acknowledging that weight alone might not give an adequate picture of someone's health, and recognizing the limitations of lifestyle interventions for weight loss, could pave the way for more effective and patient centered care, they say.

Focusing on weight loss might also contribute to societal weight bias -- negative attitudes, assumptions, and judgments about people based on their weight -- which may not only have adverse effects on mental health but may also be associated with disordered eating, the adoption of unhealthy habits, and weight gain, they add.

They point out that recent clinical guidelines reflect the growing recognition that weight is an inadequate measure of health, and alternative approaches, such as Health at Every Size (HAES), acknowledge that good health can be achieved regardless of weight loss and have shown promising results in improving eating behaviors.

While these approaches should be evaluated in large clinical trials, doctors can learn from them to provide better and more compassionate care for patients with larger bodies, they suggest.

"Doctors should be prepared to inform individuals seeking weight loss about the potential benefits and harms of interventions and minimize the risk of developing eating disorders and long term impacts on metabolism," they write. "Such a patient centred approach is likely to provide better care by aligning with patient preferences and circumstances while also reducing weight bias."

They conclude: "Doctors' advice about healthy eating and physical activity is still relevant as it may result in better health. The main goal is to offer good care irrespective of weight, which means not caring less but rather discussing benefits, harms, and what is important to the patient."