Ketosis & Depression

Depression is a mental disorder that effects close to 21 million people in the United States alone. Many variable may lead to a depressive episode, including predisposing genetics mutations, alterations in brain chemistry, and traumatic life events.

There are currently many treatments for depression available, but approximately 30% of patients with major depressive disorder (MDD) present resistance to current pharmacological therapies.  However, newer research is demonstrating that a specific diet may hold potential in alleviating depression in those resistant to the current conventional therapies.

In this blog post, we will discuss the medical application of nutritional ketosis as a novel treatment therapy for depression.

Ketosis is a deliberate metabolic state that occurs in the presence of extreme carbohydrate restriction, often less than 35g a day. This metabolic state has been shown to be an efficacious option in treating refractory epilepsy. We will explore the evidence behind ketosis as a therapeutic for depression and discuss how it could potentially be used as a first line therapy or adjuvant treatment to potentiate the effects of conventional pharmacological treatments.

Mitochondria & Depression:

The role of impaired mitochondria in depression is an area of research that has gained greater traction in the past few years due to its potential implications for understanding this complex disorder. Mitochondria are well known as the the powerhouses of cells and provide energy to support numerous cellular processes, including neurotransmission and neurogenesis. Research suggests that mitochondrial dysfunction can lead to an increase susceptibility to depression and may also be why we see a overlap between metabolic disorders and depression.

Nutritional Ketosis has been found to have an overall potent effect on mitochondria. Studies suggest that ketogenic diets can increase levels of mitochondrial respiration, enhance ATP production, and may even stimulate mitochondrial biogenesis, which is the formation of new mitochondria.

Neurotransmitters & Depression:

Neurotransmitters are chemical messengers that regulate communication between neurons and other cells and have long been associated with depression. They play an imperative role in regulating mood, cognition, and behavior. Commonly studied neurotransmitters in depression include serotonin, norepinephrine, dopamine, glutamate and GABA.

One neurotransmitter called GABA, an inhibitory neurotransmitter, has been shown to have a strong correlation with depressive symptoms.

Research has shown that nutritional ketosis has the ability to favorably potentiate GABA neurotransmission and alleviate Glutamate/GABA imbalances. This mechanism of action is likely why nutritional ketosis confers benefits for patients with refractory epilepsy.

Neuroinflammation & Depression:

While depression is probably not a purely an inflammatory condition, there is ample evidence in support of the association between depression and inflammation. This observation has been replicated several times and reviewed extensively.

The physiological byproducts of Ketosis, specifically B-hydroxybutyrate, have been shown to limit neuroinflammation in rodent models by decreasing the expression of the NLRP3 inflammasome, interleukins, and TNFa.

Microbiome & Depression:

During recent years the gut microbiota has become a hot topic in medical research as there have been a multitude of studies published examining the implication of the gut microbiome in virtually every disease.

The relationship between the gut microbiota and behavioral affect is one of the most intriguing and controversial topics in microbiome research. Growing evidence suggests that the configuration of gut microbiota may alter brain physiology and behavior in various brain disorders, including depression.

Nutritional Ketosis has demonstrated its ability to favorably alter the gut microflora in both animal models and select patient populations further increasing the mechanistic data of this diets anti-depressant effects.

Dr. Tanner Wilson is a IFM Certified Functional Medicine Provider in Kansas specializing in health optimization.