Therapeutic Ketogenic Diet Promising Treatment for Anorexia Nervosa, suggests research

AN is a chronic and fatal psychiatric disorder characterized by an extreme and idiosyncratic avoidance of food, severe emaciation, and a distorted perception of body weight. It has one of the highest mortality rates among all psychiatric disorders - especially among females aged 15-24, who are 12 times more likely to die from AN than from other causes. Conventional treatments of AN have generally had little impact since the disorder often recurs, particularly among weight-recovered patients with dysmorphic preoccupation and fear of weight gain.

Researchers establish that in AN, brain glucose metabolism is somehow altered due to increased anxiety and stress though the brain still needs more glucose. Such deviance compels the brain to function on ketones that are formed once the body enters a condition of ketosis brought about by starvation. Ketones like BHB serve not only as a substitute source of fuel for the brain but may also bring relief in anxiety symptoms and also regulate emotions.

Previously, studies reported structural and functional abnormalities in the brains of patients with AN, specifically in regions known to mediate reward processing and body image perception. These changes may underlie both chronic misperception of body size and the drive to be thin. Environmental precipitants, such as social media, may enhance these behaviors through conditioning fear responses to weight gain.

TKD is similar to fasting in that glucose and insulin are lower, and fat is converted to ketones for energy. Most of the calories from the diet come from fat, which is then broken down into fatty acids and then acetyl-coenzyme A (acetyl-CoA). After fat metabolism exceeds the TCA cycle's capacity, shunting of the acetyl-CoA to the production of ketones occurs, which is BHB and ACA among others.

This study suggests that TKD can normalize brain energy metabolism of an individual suffering from AN by permitting ketosis to be induced without the requirement for starvation. Ketones are not only a source of alternative brain energy but also the facilitation of the production of GABA from glutamate and glutamine. GABA is well known to play a crucial role in reducing anxiety and stabilization of emotional states, which would thus interrupt the cycle of starvation and anxiousness of AN.

Pilot studies have been promising with TKD. In a case report, a patient diagnosed with AN recovered with TKD followed by ketamine infusion. In a recently published open-label trial, five adults diagnosed with wrAN were placed on TKD for at least eight weeks and showed significant improvements in eating disorder-related behaviors and emotional regulation, assessed by the EDEQ and other clinical assessments.

The authors acknowledge that while TKD seems to be a promising therapeutic intervention for AN, further studies are required to validate its safety and efficacy even in larger populations and even among those patients that are remaining underweight. A subsequent follow-up study will be executed to examine the long-term effects of TKD in AN-specific behaviors as well as take a peek at possible advantages of combining TKD with other interventions, such as infusion of ketamine.

In conclusion, the neurobiological proposed model of AN combines metabolic and psychological factors that might explain how the therapeutic ketogenic diet could end the cycle of starvation and anxiety in AN. Premature data are promising but researchers caution that a more extensive set of trials should be conducted to establish TKD as standard treatment in this complex and challenging disorder.

Reference:

Frank GKW, Scolnick B. Therapeutic ketogenic diet as treatment for anorexia nervosa. Frontiers in Nutrition, 2024, DOI: 10.3389/fnut.2024.1392135, https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2024.1392135/full