Ketogenic Diet for Traumatic Brain Injury

Age: Any Age

Sex: Any

Trial Phase: Academic

Sponsor: Loma Linda University

Disqualifiers: Stroke, Psychiatric disorder, Neurological disorder, Pregnancy, Diabetes, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

30 Participants Needed

Trial Summary

What is the purpose of this trial?

Traumatic Brain Injury (TBI) represents a significant public health risk in the United States leaving many survivors with significant long term cognitive deficits and at risk for neurodegenerative diseases. Despite extensive research there are no pharmacological therapies which have demonstrated significant improvement in neurological or cognitive recovery. Changes in glucose metabolism are considered the hallmark metabolic response to TBI and ketosis has been proposed as a therapy to ameliorate metabolic dysfunction. This trial investigates the therapeutic potential of a ketogenic or modified Atkins diet on neurocognitive outcome following moderate-severe TBI.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the ketogenic diet as a treatment for traumatic brain injury?

Research suggests that a ketogenic diet may help improve recovery after traumatic brain injury by protecting brain cells and reducing inflammation. Studies in animals and small human trials have shown potential benefits, such as improved memory and reduced brain tissue damage. ^{1 2 3 4 5}

Is the ketogenic diet generally safe for humans?

The ketogenic diet has been studied for its safety and potential benefits in various conditions, including traumatic brain injury. While specific safety data for adults with traumatic brain injury is limited, the diet is generally considered safe for humans, though it may have side effects like nutrient deficiencies and gastrointestinal issues. Always consult with a healthcare provider before starting any new diet. ^{1 2 3 5 6}

How does the ketogenic diet treatment differ from other treatments for traumatic brain injury?

The ketogenic diet is unique for traumatic brain injury as it shifts the body's energy source from carbohydrates to fats, producing ketones that may protect brain cells and improve recovery. Unlike other treatments, it has shown potential in reducing brain tissue loss and inflammation, and enhancing functional outcomes, particularly in cases where standard treatments are lacking. ^{1 2 3 5 7}

Research Team

Duc Tran, MD

Principal Investigator

Loma LInda University Medical Center

Brenda Bartnik-Olson, PhD

Principal Investigator

Loma LInda University Medical Center

Eligibility Criteria

This trial is for individuals with moderate to severe traumatic brain injury (TBI) admitted to Loma Linda University's surgical intensive care unit. Eligible participants are those within 2-30 days post-injury but not pregnant, without severe speech issues, significant prior neurological disorders or interventions, acute intoxication at the time of injury, certain metabolic disorders that conflict with a ketogenic diet, history of serious mental illness, renal failure, abdominal surgery during admission, Type 1 diabetes or liver dysfunction.

Inclusion Criteria

Admitted to Loma Linda University surgical intensive care unit (SICU)

You have had a serious head injury within the past month.

Exclusion Criteria

Pregnancy

You have severe difficulty speaking or understanding language.

Your prealbumin levels are very low when you are admitted to the study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a ketogenic or modified Atkins diet to assess its impact on neurocognitive and neurological outcomes

6 months

Regular visits for dietary monitoring and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of cognitive and neurological outcomes

6 months

Periodic assessments using MR spectroscopy and neuropsychological tests

Treatment Details

Interventions

• Ketogenic Diet
• Ketogenic/Modified Atkins Diet
• Standard Diet

Trial Overview The study explores whether a ketogenic or modified Atkins diet can improve cognitive outcomes after a TBI compared to a standard diet. It aims to address changes in glucose metabolism seen in TBI patients by testing if these diets could help recover brain function.

Participant Groups

Group I: TBI KD/MAD Experimental Treatment 1 Intervention

TBI subjects on a ketogenic/modified Atkins diet

Group II: TBI SD Placebo Group 1 Intervention

TBI subjects on a standard (normal) diet

Who Is Running the Clinical Trial?

Loma Linda University

Lead Sponsor

Trials

322

Recruited

267,000+

Findings from Research

In a pilot study involving 10 adult male patients with traumatic brain injury (TBI), the ketogenic diet (KD) was found to be feasible, with 80% of participants achieving ketosis within an average of 2.2 days after starting the diet.

No significant clinical adverse effects were reported, although some patients experienced mild issues like hypertriglyceridemia and hypoglycemia, suggesting that KD may be a safe intervention for TBI management, warranting further investigation in a randomized controlled trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I single center trial of ketogenic diet for adults with traumatic brain injury. Arora, N., Litofsky, NS., Golzy, M., et al.[2022]

Rats with diffuse axonal injury (DAI) that were fed a ketogenic diet showed reduced demyelination and less axonal damage, suggesting that ketone bodies can protect myelin and support recovery after brain injury.

In laboratory tests, the ketone body β-hydroxybutyrate (βHB) improved myelination and cell survival in oligodendrocytes, indicating its potential as a therapeutic agent for preventing damage in brain injuries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketogenic diet protects myelin and axons in diffuse axonal injury. Mu, J., Wang, T., Li, M., et al.[2022]

A new ketogenic diet (KD) designed for adults significantly improved recovery from traumatic brain injury (TBI) in mice, showing reduced sensorimotor deficits and improved spatial memory over a 70-day study period.

The new-KD increased levels of Beta-hydroxybutyrate (β-HB) and enhanced the mTOR pathway, leading to reduced inflammation and tissue damage, suggesting it has therapeutic potential for treating TBI in adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A new ketogenic formulation improves functional outcome and reduces tissue loss following traumatic brain injury in adult mice. Thau-Zuchman, O., Svendsen, L., Dyall, SC., et al.[2021]

A pilot study involving 14 participants with post-concussion syndrome (PCS) tested a ketogenic diet (KD) for 2 months, showing that 11 participants successfully achieved ketosis and reported improvements in visual memory and symptom scores.

The ketogenic diet was found to be a feasible treatment option for PCS, with some participants experiencing symptom relief, although further research is needed to confirm its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Ketogenic Diet in the Treatment of Post-concussion Syndrome-A Feasibility Study. Rippee, MA., Chen, J., Taylor, MK.[2020]

A ketogenic diet (KD) significantly increased levels of beta-hydroxybutyrate and improved motor performance in rats after repetitive mild traumatic brain injury (rmTBI), indicating its potential efficacy in enhancing recovery.

KD therapy also prevented brain edema and improved neurochemical metabolite ratios, suggesting a protective role against neurodegeneration following rmTBI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton Magnetic Resonance Spectroscopy (H1-MRS) Study of the Ketogenic Diet on Repetitive Mild Traumatic Brain Injury in Adolescent Rats and Its Effect on Neurodegeneration. Zhang, F., Wu, H., Jin, Y., et al.[2018]

In a rat model of traumatic brain injury (TBI), the ketogenic diet (KD) increased the seizure threshold, meaning rats on the KD took longer to have seizures compared to those on a standard diet, particularly when the KD was maintained during seizure testing.

However, while KD reduced neuronal cell loss in the brain when administered before TBI, it did not prevent the development of epilepsy after the injury, indicating that KD may not be effective as a long-term antiepileptogenic treatment in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does ketogenic diet alter seizure sensitivity and cell loss following fluid percussion injury? Schwartzkroin, PA., Wenzel, HJ., Lyeth, BG., et al.[2017]

In a study involving 60 male Sprague-Dawley rats, the ketogenic diet (KD) significantly reduced brain edema and cellular apoptosis after traumatic brain injury (TBI), indicating its potential neuroprotective effects.

The KD was found to lower levels of the pro-apoptotic protein Bax, suggesting that it may help mitigate cell death in the brain following TBI, which could be beneficial for pediatric patients suffering from such injuries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The protective effect of the ketogenic diet on traumatic brain injury-induced cell death in juvenile rats. Hu, ZG., Wang, HD., Qiao, L., et al.[2017]

References

1. England pubmed.ncbi.nlm.nih.gov

Phase I single center trial of ketogenic diet for adults with traumatic brain injury. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Ketogenic diet protects myelin and axons in diffuse axonal injury. [2022]

3. Australia pubmed.ncbi.nlm.nih.gov

A new ketogenic formulation improves functional outcome and reduces tissue loss following traumatic brain injury in adult mice. [2021]

4. Switzerland pubmed.ncbi.nlm.nih.gov

The Ketogenic Diet in the Treatment of Post-concussion Syndrome-A Feasibility Study. [2020]

5. United States pubmed.ncbi.nlm.nih.gov

Proton Magnetic Resonance Spectroscopy (H1-MRS) Study of the Ketogenic Diet on Repetitive Mild Traumatic Brain Injury in Adolescent Rats and Its Effect on Neurodegeneration. [2018]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Does ketogenic diet alter seizure sensitivity and cell loss following fluid percussion injury? [2017]

7. England pubmed.ncbi.nlm.nih.gov

The protective effect of the ketogenic diet on traumatic brain injury-induced cell death in juvenile rats. [2017]