Scientists discovered that a combination of two natural substances—ketone bodies and glutamine—can help restore energy production in brain cells affected by a rare genetic disorder called AGC1 deficiency. This condition causes severe developmental delays, seizures, and problems with brain development. Using lab-grown brain cells from patients with this disease, researchers found that these cells struggle to produce energy efficiently. However, when they added ketone bodies and glutamine, the cells’ energy-producing structures (mitochondria) started working normally again. This finding supports why some patients improve when following a ketogenic diet, and it opens new doors for potential treatments.

The Quick Take

  • What they studied: Whether special supplements could fix energy production problems in brain cells from people with AGC1 deficiency, a rare genetic disorder affecting brain development.
  • Who participated: The study used laboratory-grown brain cells created from skin cells of patients with AGC1 deficiency. No living patients were directly involved in the experiments.
  • Key finding: When researchers added ketone bodies and glutamine together to the defective brain cells, the cells’ energy factories (mitochondria) worked normally again, producing energy efficiently just like healthy cells.
  • What it means for you: If you or a family member has AGC1 deficiency, this research suggests that a combination approach using ketone bodies and glutamine might help restore normal brain cell energy production. However, this is early-stage research, and more testing in patients is needed before this becomes a standard treatment. Talk to your doctor about whether a ketogenic diet or these supplements might be appropriate.

The Research Details

Researchers created brain cells in the laboratory by converting skin cells from AGC1-deficient patients into brain cells using special techniques. This allowed them to study what goes wrong in these cells without experimenting on actual patients. They then tested whether adding different nutrients could fix the energy problems they observed.

The scientists used advanced tools to measure how well the cells’ energy factories (mitochondria) were working, looked at which genes were active or inactive, and tested various combinations of supplements to see what worked best.

This type of study is valuable because it lets researchers understand disease mechanisms and test potential treatments in a controlled laboratory setting before considering human trials.

Understanding exactly how AGC1 deficiency breaks the cells’ energy production is crucial for developing treatments. By using patient-derived cells, researchers can study the real disease process rather than guessing. This approach allowed them to discover that the problem isn’t permanent—it can be fixed by providing alternative energy sources, which is much more hopeful than if the damage were irreversible.

This study was published in a peer-reviewed scientific journal, meaning other experts reviewed the work before publication. The researchers used established laboratory techniques and modern genetic analysis tools. However, because this work was done in laboratory cells rather than in living patients, results may not translate directly to clinical benefits. The study is preliminary and represents an important first step, but human trials would be needed to confirm these findings work in actual patients.

What the Results Show

The main discovery was that brain cells from AGC1-deficient patients have a serious energy problem: they can’t efficiently use their normal fuel (pyruvate) to power their mitochondria. Instead, these cells rely too heavily on a less efficient energy pathway called glycolysis, which is like running a car on fumes.

When researchers examined the cells’ genetic instructions, they found that the genes controlling the normal fuel-burning process were turned down or off. This explained why the cells were struggling.

The breakthrough came when researchers added ketone bodies and glutamine together. These are alternative fuels that bypass the broken pathway. When the cells had access to these alternative fuels, their mitochondria started working normally again, producing energy efficiently just like healthy cells.

This restoration of energy production also reduced cell death and improved cell growth, suggesting the energy problem was directly causing the cells to die and fail to multiply properly.

Beyond the main energy restoration, researchers observed that fixing the energy problem also reduced the amount of cell death happening in the defective cells. Additionally, the cells showed improved ability to grow and divide when given the supplement combination. These secondary improvements suggest that the energy deficit was the root cause of multiple problems in these cells, not just one isolated issue.

This research aligns with and explains clinical observations that some AGC1-deficient patients improve when following a ketogenic diet (a high-fat, low-carbohydrate diet that produces ketone bodies). Previous studies showed that AGC1 deficiency causes low levels of a brain chemical called NAA, which is important for insulating nerve fibers. This new research reveals the energy production mechanism behind that problem and suggests a way to address it. The findings build on decades of research into mitochondrial diseases and metabolic disorders.

This study was conducted entirely in laboratory-grown cells, not in living organisms or patients. Laboratory results don’t always translate to real-world benefits. The study didn’t test whether these supplements would work in actual patients or determine the right doses. Additionally, the study didn’t examine long-term effects or potential side effects of the supplement combination. The sample size and specific patient characteristics aren’t detailed in the abstract, making it difficult to assess how representative these cells are of all AGC1-deficient patients.

The Bottom Line

Based on this research, a combination of ketone bodies and glutamine shows promise for treating AGC1 deficiency (moderate confidence level, as this is preliminary laboratory research). However, clinical trials in actual patients are needed before this can be recommended as standard treatment. If you have AGC1 deficiency, discuss with your neurologist whether a ketogenic diet or these supplements might be appropriate for your specific situation.

This research is most relevant to people with AGC1 deficiency, their families, and their healthcare providers. It may also interest researchers studying rare mitochondrial diseases and metabolic disorders. People with other mitochondrial diseases should not assume these findings apply to their condition without consulting their doctor, as different mitochondrial diseases have different causes.

In laboratory cells, the energy restoration happened relatively quickly once the supplements were added. However, if this approach moves to human trials, it typically takes months to years to see clinical improvements in patients with neurological conditions. Any benefits would need to be carefully monitored by medical professionals.

Want to Apply This Research?

  • If prescribed ketone supplements or glutamine by your doctor, track daily intake amounts and timing. Also monitor energy levels, seizure frequency (if applicable), and overall well-being using a simple daily log with ratings from 1-10.
  • Work with your healthcare team to incorporate prescribed supplements into your daily routine at consistent times. If following a ketogenic diet, use the app to track macronutrient ratios (fat, protein, carbohydrates) to maintain proper ketone production.
  • Maintain a long-term health journal tracking neurological symptoms, energy levels, cognitive function, and any side effects. Share this data with your healthcare provider at regular appointments to assess whether the treatment approach is working for your individual situation.

This research describes laboratory findings in cultured cells and has not yet been tested in human patients. AGC1 deficiency is a serious medical condition requiring specialized care from a neurologist or metabolic disease specialist. Do not start, stop, or change any supplements or dietary approaches without consulting your healthcare provider first. While this research is promising, it represents an early stage of investigation. Any treatment decisions should be made in consultation with qualified medical professionals who understand your complete medical history and can monitor your response to treatment.