The Ketogenic Diet: A Recipe Against Depression?

Treatment-resistant depression (TRD) is a severe form of depression that persists despite the use of at least two adequate antidepressant treatments. This condition, affecting approximately one-third of depressed patients, represents a significant challenge in psychiatry. TRD is associated with significantly reduced quality of life, increased risk of comorbidities, including anxiety and cardiovascular diseases, and higher mortality rates.

Despite the benefits of current treatments, their effectiveness remains limited for these patients, highlighting an urgent need for alternative solutions. These new approaches must target biological mechanisms often overlooked by conventional treatments while offering innovative and personalized options.

In this context, the ketogenic diet emerges as a promising avenue to complement or enhance conventional therapies. Known for its neuroprotective effects and its beneficial impact on gut microbiota, this diet—based on low carbohydrate and high fat consumption—stimulates the production of ketone bodies. These molecules play a crucial role in regulating brain functions by improving neuronal balance, reducing oxidative stress, and modulating inflammatory processes.

This study explores the efficacy and mechanisms of the ketogenic diet as a complementary treatment for treatment-resistant depression.

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The Ketogenic Diet: A Remedy That Lives Up to Its Promises?

In this study, patients aged 18 to 65 with TRD were randomly divided into two groups:

• Ketogenic Diet Group (KD): Carbohydrate intake limited to 30g per day, with meals prepared and weekly monitoring by a dietitian. Ketosis levels were regularly measured to assess adherence.
• Control Group (Plant-Based Diet): Similar monitoring but based on a diet richer in vegetables and unsaturated fats.

The study lasted six weeks, with rigorous follow-up to evaluate participant adherence. Depressive symptoms were assessed at 6 and 12 weeks. Secondary parameters included anxiety, quality of life, reward sensitivity, and changes in gut microbiota.

Participants following the ketogenic diet showed a significant reduction in depression scores at six weeks compared to the control group. Improvements were also observed in secondary aspects such as anxiety and anhedonia.

The data also suggest that the ketogenic diet influences several biological mechanisms. It stimulates the production of the neurotransmitter GABA, essential for the balance between neuronal excitation and inhibition, thereby reducing brain dysfunctions associated with depression. Ketone bodies produced by this diet exert protective effects against oxidative stress. Beneficial changes in gut microbiota were also observed, promoting the growth of bacteria linked to better mental health.

The Ketogenic Diet: A Revolution in Progress

TRD is a severe form of depression that persists despite the use of antidepressants. Affecting about one-third of depressed patients, it leads to reduced quality of life and increased risks of comorbidities.

Faced with these challenges, the ketogenic diet appears as an innovative approach, targeting biological mechanisms such as neurotransmitter balance, oxidative stress reduction, and gut microbiota improvement. This study aimed to evaluate its efficacy and potential as a complementary treatment by comparing a ketogenic diet group with a control group receiving a more conventional diet.

The results show that the ketogenic diet significantly improves depressive symptoms, particularly anxiety and anhedonia. However, its impact depends on strict adherence, which poses a significant challenge for its clinical implementation.

Larger-scale studies with extended follow-up are necessary to confirm these findings and identify strategies to enhance patient adherence. If these obstacles are overcome, the ketogenic diet could expand current therapeutic options, offering a promising new path for patients with TRD.