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McCabe, Room 215

Health Studies 4400 Massachusetts Avenue NW Washington, DC 20016 United States

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Nutritional Neuroscience Lab

The main focus of the Nutritional Neuroscience Lab is studying how food additives negatively influence neurotransmission, and how dietary nutrients may help prevent excitotoxicity. We are especially interested in how exposure to dietary excitotoxins can lead to neurological symptoms, including pain, cognitive dysfunction, paresthesia, gastrointestinal disorders, memory loss, inattention, impulsivity and centrally mediated fatigue; as well as psychiatric symptoms like depression, anxiety, PTSD and attentional difficulties.

Excitotoxins are amino acids in the diet which also function as excitatory neurotransmitters in the nervous system. These amino acids, when present in high enough amounts, have the ability to over-excite a neuron to the point that it dies. Even in smaller amounts, exposure to excitotoxins may lead to abnormal excitatory neurotransmission. Excitotoxicity also leads to increased production of reactive oxygen species and oxidative stress in cells, which in turn, increases the demand for dietary antioxidants.

The most common exposure to dietary excitotoxins comes from the use of free amino acids as food additives. The most well-known food additives in this class are monosodium glutamate (MSG) and aspartame (which is a dipeptide of phenylalanine and aspartate), though there are many others hidden under various names on food labels. Any food which contains free forms of glutamate, aspartate or L-cysteine has the potential to elicit symptoms in sensitive individuals; however, there are also foods like soy sauce and parmesan cheese which naturally contain higher levels of these amino acids. Extremely potent glutamate analogs also exist in the environment, but exposure to these chemicals is not as common.

In prior research, we have demonstrated that individuals with fibromyalgia and irritable bowel syndrome had >30% of their symptoms remit after one month on a low glutamate diet, with symptom return upon double-blind placebo-controlled crossover challenge with MSG as compared to placebo. We are now working to understand the mechanism behind why these individuals may be more susceptible to these food additives than the general population.

Our lab is also studying the effects of diet on ADHD. We have conducted research on the impact of micronutrient and amino acid consumption in ADHD, as well as the potential contribution of food additives to the symptoms of ADHD in college students, including artificial food coloring and the potential for dietary modulation of the NMDA glutamate receptor.

Our lab is striving to advance the understanding of dietary influences on excitotoxicity. In addition to widespread chronic pain and ADHD, disordered glutamatergic neurotransmission has been implicated in many disorders including: Alzheimer's, Parkinson’s, Multiple Sclerosis, epilepsy, migraine, depression, anxiety, obsessive compulsive disorder, PTSD, and others. Thus, the mission of our lab is to elucidate the potential impact of dietary excitotoxins on neurological/psychiatric symptoms, as well as the positive protective effects of specific dietary components including micronutrients, antioxidants and omega-3 fatty acids.

Current Study

We have just finished recruiting 40 veterans from around the US for our current Gulf War Illness (GWI) study funded by the Department of Defense. This study is evaluating whether a low glutamate diet can be used as an effective treatment for the chronic symptoms of GWI including widespread chronic pain, headache/migraine, cognitive dysfunction, mood dysregulation, sleep issues, and gastrointestinal symptoms. The data collected is being cleaned and analyzed, and the first publications from this research are expected in Summer 2020. If you are a Gulf War veteran who missed out on participating in this clinical trial, but are interested in future GWI clinical trials, please call or email the lab so you can be added to our wait-list.

Upcoming Studies

We are recruiting for an upcoming clinical trial that will assess the effectiveness of a low glutamate diet for pediatric refractory epilepsy. Glutamate is found in the diet as a flavor enhancer; and is also an important neurotransmitter in the body which mediates seizure activity. The low glutamate diet is balanced, nutritious and palatable, with no side effects. Additionally, the diet provides all nutrients necessary for optimal growth and development, as well as optimal brain function. The study is investigating if following the low glutamate diet for 1 month can improve seizure frequency, severity, and duration; cognitive functioning; and/or quality of life, in children with epilepsy. We will also be looking at changes in brain wave activity. Participation in the study will include 2 visits to the Nutritional Neuroscience Lab at American University over a 2- or 3- month study period, depending on group randomization. Eligible participants include children who are 4-18 years of age, who are experiencing at least 1 seizure per week, have had unsuccessful seizure control with 2 or more anti-epileptic drugs, are orally fed, and do not have inborn errors of metabolism.

If you would like more information or to see if your child may qualify to participate in this study, please call or email the Nutritional Neuroscience Lab with the following information:

  • The study you are interested in (epilepsy study)
  • Name
  • Phone number
  • Email address

Selected Publications and Talks

Brandley, E.T., & Holton, K.F. Breakfast positively impacts cognitive function in college students with and without ADHD. American Journal of Health Promotion. In Press Jan 2020. 

Holton KF, Kirkland AE. Moving past antioxidant supplementation for dietary treatment of multiple sclerosis. Multiple Sclerosis Journal. In Press.

Holton KF, Hargrave S, Davidson TL. Differential Effects of Dietary MSG on Hippocampal Dependent Memory Are Mediated by DietFront Neurosci. Sept 2019.

Kirkland AE, Holton KF. Measuring treatment response in pharmacological and lifestyle interventions using electroencephalography (EEG) in ADHD: A review. Clinical EEG and Neuroscience. In press. Nov 2018. DOI:10.1177/1550059418817966

Kirkland AE, Sarlo GL, Holton KF. The Role of Magnesium in Neurological Disorders. Nutrients2018 Jun; 10(6):730. DOI:10.3390/nu10060730 

Holton KF, Ndege PK, Clauw DJ. Dietary correlates of widespread chronic pain in Meru, Kenya. Nutrition. 2018 Feb; 53:14-19. DOI:10.1016/j.nut.2018.01.016

Holton KF, Cotter EW. Could dietary glutamate be contributing to symptoms of Obsessive-Compulsive Disorder? Future Science OA. 2018 Jan; 4(3):FSO277.

Holton KF, Johnstone JM, Brandley ET, Nigg JT.  Evaluation of Dietary Intake in Children and College Students with and without Attention-Deficit/Hyperactivity Disorder. Nutr Neuroscience. 2018 Jan; 23:1-14. DOI:10.1080/1028415X.2018.1427661

Brandley ET, Kirkland AE, Sarlo G, VanMeter J, Baraniuk J, Holton KF. The Effects of a Low Glutamate Dietary Intervention on Anxiety and PTSD in Veterans with Gulf War Illness (FS15-08-19). Curr Dev Nutr. 2019 Jun; 3(S1). (Peer reviewed podium presentation and published abstract)

Kirkland AE, Holton KF. Intake of Aspartate Is Negatively Associated with Overall Cognitive Functioning in College Students (P14-015-19). Curr Dev Nutr. 2019 Jun; 3(S1). American Society for Nutrition, Baltimore, MD. (Peer reviewed poster and published abstract)

  • Oral and poster presentation (student) at the American Epilepsy Society conference in Baltimore, MD Dec 6-10, 2019 titled, “Optimization of Data Collection for Clinics Specializing in Dietary Therapies for Epilepsy”

  • Poster presentation (student) at the International Conference on ADHD in Philadelphia, PA Nov. 6-9, 2019 titled, “Artificial Food Coloring Affects Brain Wave Activity in College Students with ADHD”
  • Oral presentation at the International Society for Nutritional Psychiatry Research in London, England Oct 20-22, 2019 titled, “A Low Glutamate Diet Reduces Anxiety and PTSD Symptoms in Veterans with Gulf War Illness”
  • Poster presentation (student) at the International Society for Nutritional Psychiatry Research in London, England Oct 20-22, 2019 titled, “The Effects of a Low Glutamate Diet on Depression in Gulf War Veterans”
  • Symposium presentation at the International Society for Nutritional Psychiatry Research in London, England Oct 20-22, 2019 titled, “Micronutrients for Mental Illness”
  • Symposium presentation at the International Society for Research on Child Psychopathology in Los Angeles, CA June 26-29, 2019 titled, “Broad Spectrum Micronutrient Treatment for Children with ADHD and Irritable Mood: Why, How, Results, and Future Directions”
  • Oral and poster presentation (student) at the American Society for Nutrition conference in Baltimore, MD June 8-11, 2019 titled, “The Effects of a Low Glutamate Dietary Intervention on Anxiety and PTSD in Veterans with Gulf War Illness”
  • Poster presentation (student) at the American Society for Nutrition conference in Baltimore, MD June 8-11, 2019 titled, “The Effects of a Low Glutamate Dietary Intervention on Anxiety and PTSD in Veterans with Gulf War Illness”
  • Poster presentation (student) at the American Society for Nutrition conference in Baltimore, MD June 8-112019 titled, “Intake of Aspartate and Glycine is Negatively Associated with Cognitive Functioning in College Students”
  • Poster presentation (student) at the Society for Research on Child Development Biennial Meeting in Austin, TX April 6-8, 2017 titled, “The effects of breakfast on cognitive function in college students with and without ADHD”