Thread by @KetoCounselor

Let's explore the outcomes of a study that explored the neurobiological evidence in support of improvement in depression with a ketogenic diet and find out what underlying biological mechanisms they uncovered through in vitro and in vivo studies.🧵(1/29) #depression #ketogenic

Basically, they did a literature review from August 2021 to January 2022. Here's what they found. (2/29) #research

People with #depression may have changes in #glucose #metabolism in the brain. The #ketogenic diet boosts cellular #energy metabolism by raising #ketone bodies and replacing glucose as the main fuel source. (3/29)

This may restore mitochondrial function and help maintain energy balance. The #ketogenic diet, which relies on ketone bodies instead of glucose, could be a promising approach. (4/29)

The glutamate/GABA system is implicated in depression. Studies have shown altered glutamate levels in depressed individuals, suggesting excessive glutamate-induced excitation in depression. (5/29) #neurotransmitters #neurotwitter

Reduced GABAergic activity accompanies depression, similar to epilepsy. Ketosis, which enhances astrocyte metabolism and increases glutamate removal, might explain the efficacy of ketosis in treating both epilepsy and depression. (6/29) #ketosis #brainhealth

#Mitochondria are responsible for energy metabolism in cells, and their reduced function is implicated in the pathogenesis of neurodegenerative diseases, which may contribute to depression. (7/29)

Ketosis may help alleviate depression by impacting mitochondrial and oxidative processes, ultimately improving brain function. (8/29)

The induction of low redox signaling molecules triggered by ketone bodies may increase the levels of antioxidants and detoxification enzymes, (9/29)

and it is thought that this potentially reduces the oxidative stress and mitochondrial dysfunction associated with depression. (10/29) #Depression #Ketosis #OxidativeStress #Mitochondria

The authors found many studies suggesting a strong association between depression and inflammation and also acknowledged it is likely not a purely inflammatory condition. (11/29)

Microglial alterations are thought to play a critical pathophysiological role in depression. β-hydroxybutyrate promoted microglial ramification in mice with depressive behavior. (12/29)

This finding, and many more outlined in their investigation of the scientific literature, provide evidence for the antidepressant effects of ketone bodies via their immunomodulatory actions. (13/29) #depression #inflammation #immunomodulation

Depression may have a causal link with the gut microbiota, as shown in animal model-based studies. Microbiome alterations seen in depressed patients are similar to those found in other chronic diseases such as metabolic syndrome. (14/29)

A ketogenic diet may help restore microbial balance in the gut, potentially alleviating the burden of depressive symptoms. Animal models and patients with brain disorders have shown promising results. (15/29)

These findings identified in the scientific literature provide a strong rationale for studying the effects of a ketogenic diet on the gut microbiota and symptom improvement in patients with depression and animal models with depression-like behaviors. (16/29)

Depression is a complex human phenomenon that can be difficult to study, but animal studies have provided valuable insights into potential pathophysiological mechanisms and clues for novel treatments for Major Depressive Disorder. (17/29)

In rat models of depression-like behaviors, a ketogenic diet improved "behavioral despair", indicating that ketosis could improve depressive symptoms. (18/29)

In other animal studies, feeding ketone salt and ketone salts mixed with medium-chain triglycerides improved anxiety-associated behaviors in Sprague-Dawley and WAG/Rij rats, achieving ketosis within seven days. (19/29)

Interestingly, in a mice study, exposure to a gestational ketogenic diet modulated the offspring's brain structures and protected them against anxiety and depression-associated behaviors later in adulthood, even though the offspring were fed a standard chow after birth. (20/29)

Furthermore, recent animal studies demonstrated that a ketogenic diet with regular exercise decreased anxiety and depressive behaviors in mice. The reduction in depression burden was correlated with BHB levels, linking mood improvement to favorable metabolic changes. (21/29)

While the evidence for the improvement in depressive symptoms and the underlying mechanisms is limited, the existing data are encouraging and warrant further mechanistic studies on the beneficial neuromodulator effects of ketosis. (22/29)

At the time this article was published, there were no RCTs investigating ketogenic diets and depression! But I know of at least one going on! So what did this study find out based on what was currently out there at the time around ketogenic diets for mood and cognition. (23/29)

A randomized controlled study found that a ketogenic diet reduced anxiety and improved mood and cognition in children and adolescents with refractory epilepsy compared to a regular diet with standard care. (24/29)

And in adult patients with chronic epilepsy, a ketogenic diet was associated with lesser anxiety and depression. (25/29)

The longer they were on the diet, the more favorable impact on their psychological state. I think that's pretty cool. (26/29)

A case study demonstrated that a ketogenic diet might act as a mood stabilizer in patients with type II bipolar disorder. Patients achieved mood stabilization superior to that accomplished using medication. (27/29)

You can read the conclusion yourself here. I don't want you to think I just made all this up🤷‍♀️(28/29)
lidsen.com/journals/rpn/r…

The authors state the keto is an established treatment for comorbidities & pathologies seen in depression, but we need more RCTs for specific MDD groups. Thanks to @baszuckigroup & partners for funding! Without them, no one would know how to feel better! #mentalhealth (29/29)