Glucagon-like peptide-1 (GLP-1) agonist medications such as semaglutide (Ozempic, Wegovy) and tirzepatide (Zepbound, Mounjaro) have taken the world by storm over the past few years. People are losing tremendous amounts of weight and improving certain chronic medical conditions when all else has failed to help. Yet, it was an accident that GLP-1s were rediscovered as a tool
We have had GLP-1 medications on the market for a long time now, such as in the form of liraglutide (Saxenda). Liraglutide was first approved by the FDA in 2010 to improve blood glucose in patients with type 2 diabetes, but studies of the drug hinted at the weight loss potential offered by GLP-1s via its 5 and 10% weight loss compared with placebo. However, only more recently was that potential taken seriously as an intervention in and of itself. Today, GLP-1s are seen as a game-changer for the world's growing obesity problem.
This brings us to the ketogenic, or "keto" diet, which has traditionally been used for weight loss and fitness. It has taken the health and fitness sector by storm in waves over the years, and routinely stirs controversy. The keto diet is highest in fats, moderate in protein, and extremely low in carbohydrates. While exact amounts of each macronutrient can differ and there are multiple variations, a general rule is to keep carbohydrate intake extremely low (as low as 20 grams of net carbohydrate intake daily in some cases).
What is less well-known are the promising results of the keto diet in the medical literature across a variety of specialties. Beyond its effectiveness in weight loss, it has also shown risk reduction benefits for heart health, cancer, and even epilepsy. Even less well known is that in psychiatry, there is emerging research showing its impact on schizophrenia and bipolar disorder, and more recently in obsessive-compulsive disorder. Remarkably, some patients even claim the diet has brought to complete remission cases of the most treatment-resistant psychiatric conditions -- a claim actively sought by pharmaceutical companies for their drugs.
One case series showed success of the ketogenic diet for patients with a serious treatment-resistant psychiatric condition: anorexia nervosa. This is a condition in which patients will restrict eating for prolonged periods of time, which leads to it being the deadliest psychiatric condition. Patients with severe anorexia nervosa can routinely spend years pursuing treatments in inpatient medical and psychiatric units, eating disorder-specific units, structured outpatient group programs for eating disorders, and outpatient care with multiple individual specialists from various specialties, including psychiatry and adolescent medicine.
Published in the Journal of Metabolic Health, the case series follows three patients with anorexia nervosa who developed sustained improvements in their condition over the course of multiple years after starting the keto diet intervention. Over 1, 2, and 5 years, these three patients each ultimately gained at least 20 kilograms (about 44 pounds) of weight, with sustained weight restoration over those time frames. It is important to note that these were severe, treatment-resistant cases -- they suffered with anorexia for many years, and because of their conditions, these patients had developed multiple medical problems that directly resulted from food restriction, including osteoporosis, hypogonadism, and multiple organ prolapses treated with surgical interventions.
As a psychiatry resident, I am naturally fascinated by this promising potential of the keto diet. This may be a true disease-modifying intervention -- perhaps comparable to the likes of a medication such as lithium for bipolar disorder. Despite this, keto has long been overlooked.
So, how does it work? Theories point to ketones' effects in improving the health and functioning of mitochondria, brain neural energy metabolism, and immune response throughout the body.
However, we will need more than case reports and series in order to determine true efficacy and for this intervention to gain traction. Some groups are already working on clinical trials.
I believe the keto diet has the potential to become one of the most serious breakthrough treatments in psychiatry. It could entirely redefine psychiatric "treatment-resistance" as we know it. Of course, there are certainly weaknesses to the keto diet, such as with stigma, lifestyle change, and long-term adherence -- especially within populations that face significant socioeconomic barriers. But I believe the keto diet can completely change lives if it were to be adopted more readily in psychiatric practice.
It is only a matter of time before the keto diet takes the world by storm as GLP-1s recently have, to potentially spur a new revolution as the "Ozempic" or "Zepbound" of psychiatry.
Zane Kaleem, MD, is a fourth-year psychiatry resident at Penn State Milton S. Hershey Medical Center in Hershey, Pennsylvania.
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