For more than 50 years, researchers have examined the effect of a ketogenic diet on patients with behavioral health disorders.1 Despite this breadth of research, most of the studies have lacked depth, consisting mostly of case reports, animal studies, and small-sample open studies rather than controlled trials.1 Although researchers remain cautious, a review of research reveals that the popular diet may hold some promise for individuals with mental health disorders.

How Does the Ketogenic Diet Affect the Brain?

The ketogenic diet is an established option for treatment-resistant epilepsy, as evidenced by a range of studies, including controlled trials.1 The diet also has shown promise for managing other brain-based disorders, such as Parkinson disease, amyotrophic lateral sclerosis, traumatic brain injury, multiple sclerosis, and chronic headaches as well as for metabolic disorders such as obesity, cancer, and type 2 diabetes.2

Unfortunately, it is unclear how ketogenic diets work to control seizures, let alone how they may improve psychiatric symptoms.2 It may pertain to the presence of ketones, reduction in blood sugar, reduction in insulin and other growth-promoting hormones, or the combination of all of these.2 Other theories include altered neurotransmitter levels, changes in electrolyte gradients (lower intracellular sodium and calcium), reduction in markers of inflammation, and improved mitochondrial function.2

“The general consensus is that the brain functions more cleanly and efficiently when a significant portion of its energy comes from ketones, calming overactive and overly reactive brain cells,” Georgia Ede, MD, a board-certified psychiatrist specializing in nutrition-focused counseling, explained in Psychology Today.2

What the Research Reveals

A review of the literature reveals the following about the ketogenic diet’s reaction with diseases1:

  • Anxiety: Exogenous ketone supplementation reduced anxiety-related behaviors in a rat model.
  • Attention-deficit/hyperactivity disorder: In a controlled trial of the ketogenic diet in dogs with comorbid epilepsy, both conditions significantly improved.
  • Autism-spectrum disorder: An open-label study in children reported no significant improvement, yet one case study reported “a pronounced and sustained response.” Further, in 4 controlled animal studies, the ketogenic diet significantly reduced autism-related behaviors in mice and rats.
  • Bipolar disorder: One case study reported a reduction in symptomatology whereas a second case study reported no improvement.
  • Depression: The ketogenic diet significantly reduced depression-like behaviors in rat and mice models in 2 controlled studies.
  • Schizophrenia: An open-label study in female patients found reduced symptoms after 2 weeks of the ketogenic diet whereas a single case study reported no improvement; however, 3 weeks of the ketogenic diet in a mouse study normalized pathological behaviors.

The Bostock review did not include studies regarding how the ketogenic diet affects dementia and Alzheimer disease. A 6-week study of a low-carbohydrate diet in persons with mild cognitive impairment saw improvement in verbal memory, with greater benefits for persons who achieved higher ketone levels.2 The cognition and function of a man with Alzheimer disease “significantly improved” with the use of ketone supplements during a 20-month case study.2

A review of the effect of the ketogenic diet on patients with epilepsy concluded that3:

  • Subjective assessment of patients found cognitive improvements with the ketogenic diet treatment, particularly in the domains of alertness, attention, and global cognition;
  • Studies that used objective neuropsychological tests, however, confirmed benefits in alertness but found no improvement in global cognition;
  • The duration of the ketogenic diet treatment appears to have a positive effect on the degree of cognitive improvement; and
  • Because patient compliance with the ketogenic diet is generally low, this may lead to a bias in the research.

Researchers Urge Caution

According to researchers, there are several reasons why the effectiveness of the ketogenic diet in mental disorders is difficult to prove1:

  • Low number of human studies
  • Low quality of the studies (sample sizes are small, no control for placebo effects, no consistent measurement of ketosis, lack of detail about the specifics of the diet and duration)
  • No enforced standards as to what constitutes the ketogenic diet in humans
  • Ketogenic diet monotherapy is largely unexamined in human studies
  • The ketogenic diet requires patients who may be ill to measure food portions
  • Diet compliance can be difficult, particularly for patients with mania, apathy, reduced appetite, food cravings, or binge eating issues

The ketogenic diet may also cause adverse effects, including1,2:

  • Constipation
  • Elevated liver enzymes and/or abnormal liver function
  • Elevated serum cholesterol
  • Elevated triglycerides
  • Emesis
  • Gallstones
  • Hemolytic anemia
  • Hypoglycemia
  • Hypoproteinemia
  • Kidney stones
  • Leg cramps
  • Menstrual irregularities
  • Periorbital edema
  • Presacral edema
  • Renal tubular acidosis
  • Thrombocytopenia
  • Unwanted weight loss
  • Viral gastroenteritis

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Dr Ede agreed that the research is not there — yet.

“Nutrition studies are hard. Blinding is nearly impossible, funding is hard to come by, compliance is challenging, and controls are difficult to design,” Dr Ede explained.2 “Fear, bias, and nutrition miseducation limit the number of scientists interested in and willing to conduct studies of low-carbohydrate, high-fat diets. We clearly need high-quality human studies exploring the effects of ketogenic diets on mental health disorders, as many clinicians and patients will be afraid to utilize this diet without stronger evidence.”2

Most researchers agree that low-carbohydrate diets can help stabilize brain chemistry, particularly for patients who are not responding to other treatments. Psychiatrists interested in recommending the ketogenic diet to a patient may benefit from consulting with a dietitian or primary care provider with expertise in ketogenic diets.2

References

  1. Bostock EC, Kirkby KC, Taylor BV. The current status of the ketogenic diet in psychiatry. Front Psychiatry. 2017;8:43.
  2. Ede, G. (2017). Ketogenic diets for psychiatric disorders: a new 2017 review. Psychology Today. [Accessed 9 Aug. 2019].
  3. van Berkel AA, Ijff DM, Verkuyl JM. Cognitive benefits of the ketogenic diet in patients with epilepsy: a systematic overview. Epilepsy Behav. 2018;87:69-77. 

This article originally appeared on Psychiatry Advisor