Anorexia Nervosa is an eating disorder that can affect people of all ages, genders, sexual orientations, races, and ethnicities. It is characterized by extreme weight loss and consequent difficulties maintaining an appropriate body weight for the height and age of the sufferer. It is not a new condition, and many historians believe there is evidence to suggest that individuals have been displaying symptoms of anorexia for hundreds or even thousands of years. Treatment plans are often tailored to the individual patient and can range from cognitive behavioural therapy, a hospital stay, psychotherapy and help from a registered dietitian. However, despite these treatments, recovery is a long process.

In this piece, we have the privilege of taking a look at a new potential treatment option for Chronic Anorexia Nervosa, from the three viewpoints – the author of a compelling research article, the Faculty Member who recommended the work, and the patient involved in the study. Let’s introduce these participants:

Barbara Scolnick is a semi-retired internist who lives in Boston, MA. She graduated from Columbia College of Physicians & Surgeons in 1977. During this time she often worked part-time in outpatient clinics and also raised 3 children.

Caroline Beckwith is Barbara’s niece and the patient in this study. She has a Bachelor’s Degree from the University of Wisconsin Madison and half of a Master’s Degree from Columbia University Teachers College. Her Anorexia and addiction ultimately made finishing this program pretty impossible.

Maria Consolata Miletta is an Associate Faculty Member for Faculty Opinions who works with Tamas Horvath to evaluate the literature relevant to their research interests. She is currently a group leader at the University of Zurich. Her main research interests are the neurobiology of anorexia nervosa and she hopes that one day she can study the condition at a single-cell resolution and begin to lay the foundation of an effective cure.

*This study was conceptualized and implemented by Prof. Tamas Horvath, Faculty Member, principal investigator and last author on the paper, and performed in his lab at the Yale School of Medicine.

What sparked your interest in researching Anorexia Nervosa?

BS: Everything changed 15 years ago when my niece Caroline Beckwith was 14 years old. Since her mother and I are identical twins, our families are very close. Caroline was funny, athletic, easy-going, and in general a pleasure to be around, until she developed anorexia nervosa, and was swallowed up, not to emerge for 15 years. Once she developed anorexia nervosa, I tried to find answers.

MM: My main research interest at the end of my PhD was the physiology of fasting: specifically, what happens to our body when we fast and how long can we? Hence I contacted Prof Tamas Horvath, a worldwide expert in the field and I moved to Yale for a postdoc in his lab. He has been studying for 25 years a family of neurons physiologically active during fasting called AgRP neurons. The hypothesis was that these neurons might be involved in the development of Anorexia Nervosa. There were some supportive data from clinical studies too. Patients suffering from Anorexia have a high level of circulating AgRP protein in the blood for example. These neurons are located in the hypothalamus, a deep region in the brain mainly involved in feeding behavior.

The project was risky but we really surprised by the results. We found that AgRP neurons, when activated in an activity-based anorexia model, modulate a complex response that involve both metabolic and behavioral changes to adapt to fasting.

What is your relationship with the study “Remission from Chronic Anorexia Nervosa With Ketogenic Diet and Ketamine: Case Report”?

BS: This entire project was dependent upon my easy access to PubMed, initially at the Harvard medical school library, and then my home computer. I used this tool to read papers of scientists who worked at different decades and disparate fields—lipid research, hibernation, brain histology. Among the influential scientists was Ralph Holman who described the skewed fatty acid profile seen in patients with anorexia nervosa. Shan Guisinger authored “Adaptation to Flee Famine” and noted that patients with anorexia nervosa and migrating mammals both engage in constant motion and minimal eating, and suggested that anorexia nervosa was a manifestation of an ancient adaptation to fleeing famine.

Discovering that an animal model of anorexia had been described since the 1960s was eye-opening. The activity-based anorexia rodent model of anorexia nervosa was based on the observation that some rodents when placed in a cage with a running wheel and subjected to a slight decrease in the food supply, proceed to hyper-exercise and reject all food, and actually starve to death if not removed from the cage. This self-starvation required both stimuli; the running wheel and decreased food supply.

The most important message is that: Anorexia is not a choice. There is so much stigma in society for people suffering from Anorexia and this might delay getting the most appropriate treatment or even getting appropriate funding for research. Patients do not choose to starve to death.

Maria Miletta, Group Leader, Department of Neonatology, University of Zürich.

I wondered if a faulty brain circuit responsible for recognizing the ambient food supply might be the underlying pathology in anorexia nervosa. One could hypothesize, that this “faulty circuit” would be asymptomatic unless the patient experienced an initially minor episode of insufficient nutrition, and then, unfortunately, it would become obvious. Hibernation is an adaptation that requires the mammal to recognize and anticipate changes in ambient food supply so I focused my reading on hibernation.

The ketogenic diet has been shown to be an effective treatment for seizure disorders since it was described in 1921. While the exact mechanism of action remains unknown, the diet causes the brain energy supply to shift from being dependent on glucose to being driven by ketones. This is a fundamental change which alters many pathways. When I found articles from 1970s, that suggested the ketogenic diet was useful in the activity-based anorexia model, I wondered why it was not tried in humans. It seemed to tie the pieces together.

MM: Currently, there is no effective treatment for anorexia. It is worrisome because it is the psychiatric disorder with the highest mortality (almost 10% according to the national institute of mental health). Actual treatment involves the restoration of the normal body weight, addressing the abnormal behaviors that promote and support this eating disorder, often a parallel treatment with antidepressants. 20% of patients will develop chronic anorexia. This study report is interesting because find a long-term strategy that can help in both managing the weight and the psychiatric symptoms (phobia to eat, compulsive behaviors). Certainly, to be considered effective, the treatment should be extended to a greater number of patients.

What were the limitations and challenges of this study?

BS: I was so excited to come up with something that might help Caroline. The disappointment was severe when no one in academia would research these ideas, and few would even entertain them. Ketogenic diets are commonly used for weight loss, so it was thought to be contraindicated. Ketamine was more palatable to the “specialists” I reached out to, but the doses considered by the academics who were treating depression with ketamine were lower than those used in the Mills study.

It feels absolutely fantastic to be recommended by Faculty Opinions. This recommendation, which is from an excellent basic scientist has given us all a very needed boost. It is wonderful to have basic scientists and clinicians work together.

Barbara Scolnick MD, Associate Investigator, Clinical Trial Ketogenic Diet/Ketamine for Anorexia Nervosa

BS: Caroline was nearing 30. She had been ill for 15 years. While her weight was nearly normal, she was consumed with compulsions to exercise and to eat in a ritualistic manner. It was not a life worth living, in her opinion. We could not wait for academics. Caroline and I talked, and walked endlessly through the streets of New York City in the pre-COVID months of 2019. Finally, we simply tried it ourselves, with the help of two great clinicians.

Beth Zupic-Kania is a nutritionist who has been treating children with seizure disorders with the ketogenic diet for a decade and graciously agreed to help us. Lori Calabrese is a psychiatrist who has used ketamine infusions to treat suicidal depression. We simply gave it a try and hoped for the best. Caroline’s response was so amazing, we were all stunned. After 4 weeks on the ketogenic diet, and 3 ketamine infusions, the anorexia nervosa related thoughts, behaviors, compulsions dissolved, and she remains in complete remission now over 12 months since the intervention.

CB: The largest, most obvious challenge, was convincing the anorexic voice in my head to allow me to eat fat. Anorexia has so many rules, but the strictest for me was to avoid high-fat food. If it was not avoidable, then I had to exercise the calories away. This voice in my head was with me every second of every day, so as I learned about the keto diet, anorexia did as well. The voice wakes up in the morning with you and starts to tell you your day. “First we’ll make coffee then we’ll do squats then we’ll do push-ups then we will go for a walk etc” ALL day. I found by eating a high fat “keto” breakfast first thing in the morning, before anything else, made anorexia quieter throughout the day. Getting myself to do this was hard, but not impossible.

There was a time in the beginning when I stopped eating keto and went back to eating what anorexia wanted me to eat (lots of walking down the streets of NYC while eating m&m’s and frozen yogurt) and this made it very clear that the high-fat diet was truly helping. I think I had to “go back” to be fully convinced that going forward with keto was the way out of anorexia. After that, eating this way became much easier.

I felt empowered every morning when I would wake up and eat bacon, eggs, avocado, and get to say “you can’t scream at me right now,” to anorexia. By the time I got the ketamine infusions, I had whole chunks of time in the day that were quiet from anorexia. It was not gone, but I could feel how much weaker it was from the diet.

MM: There is currently a growing body of evidence which shows that there is an area of the brain involved in the aetiology of anorexia, but isn’t necessarily under the conscious control of the brain. The combination of ketogenic diet and ketamine might surprisingly work in synergy with behavioral therapy because it targets these deep areas of the brain.

The largest, most obvious challenge, was convincing the anorexic voice in my head to allow me to eat fat. Eventually, I felt empowered every morning when I would wake up and eat bacon, eggs,avocado, and get to say "you can't scream at me right now," to anorexia. By the time I got the ketamine infusions, I had whole chunks of time in the day that were quiet from anorexia. It was not gone, but I could feel how much weaker it was from the diet.

Caroline Beckwith, Research Assistant, Clinical Trial Ketogenic Diet/Ketamine for Anorexia Nervosa

What is one thing you would like the average person to know about Anorexia Nervosa?

CB: I think people do not realize how much of a person’s life is stolen from anorexia. Looking back, I cannot believe I was allowed to go to college, live alone, feed myself, and have any chance of success.

I think the “average person” imagines someone with anorexia as a rail-thin ballerina or model. I think the easiest way to identify if someone has it is if they are clearly “following rules” that are punishing and isolating and do not appear to be in their best interest. Of course, I didn’t want to wake up at 4am and go on the elliptical machine for three hours! I just didn’t have a choice, and anorexia would not allow me to tell anyone this.

Anorexia is not a choice, or a “control issue”, or the result of some family trauma. It is completely out of control to anyone who has it, and they do not want it, but the voice tells you to keep that all a secret.

MM: The most important message is that: Anorexia is not a choice. There is so much stigma in society for people suffering from Anorexia and this might delay getting the most appropriate treatment or even getting appropriate funding for research. Patients do not choose to starve to death.

How does it feel to have your work recommended by Faculty Opinions?

BS: Absolutely fantastic. Most of the eating disorder community is absolutely shunning this idea, and I have gotten some very nasty emails, claiming it is absurd to use a diet to treat anorexia nervosa. This recommendation, which is from an excellent basic scientist has given us all a very needed boost. It is wonderful to have basic scientists and clinicians work together. As far as our pilot clinical trial, we will persist, and we will do it safely, and we will get answers.

If you’re interested in learning about research in this area, then you can read more in our Eating Disorder and Clinical Nutrition Sections. You can also follow our Associate Faculty Member, Maria Miletta.

Hannah Towfiq

Hannah Towfiq

Hannah is the Social Media & Content Manager at Faculty Opinions and Sciwheel. Her background is based in science and healthcare, which she utilises to communicate complex subjects in insightful and approachable formats, through our blogs and social platforms.

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