Tired Brain, Low Mood? It Could Be Mitochondria

Author: Rohan Smith | Functional Medicine Practitioner | Adelaide, SA

Quick Answer

Mitochondria fatigue mood are closely connected, and many people don’t realise that chronic tiredness, low energy, brain fog and low mood can stem from impaired mitochondrial function. Mitochondria are the powerhouses of your cells, responsible for producing cellular energy (ATP), and when they aren’t working optimally, your body struggles to keep up with physical and mental demands. In this article, we explore how mitochondrial dysfunction can contribute to fatigue and mood imbalances, and why conventional testing often misses these deeper drivers.

Persistent low mood, brain fog, and mental fatigue may be linked to impaired mitochondrial function, particularly when these symptoms occur alongside chronic fatigue, poor stress tolerance, or unexplained physical exhaustion (1–3).

Mitochondria generate cellular energy in the form of adenosine triphosphate (ATP), which the brain relies on heavily. When energy production is disrupted, neurotransmitter signalling, inflammation regulation, and cognitive performance can be affected—potentially contributing to mood symptoms in some individuals (4–6).

Core Concept: Why Brain Energy Matters for Mood

Mitochondria are intracellular organelles responsible for producing ATP, the primary energy currency of the body. Although the brain represents only around 2% of total body weight, it consumes approximately 20% of the body’s total energy output (6).

Because of this high demand, even subtle impairments in cellular energy metabolism may disproportionately affect cognitive and emotional function. This includes pathways related to cellular energy metabolism and methylation, which influence mitochondrial efficiency and neurological function.

Research has increasingly linked mitochondrial dysfunction with depression, anxiety, cognitive fatigue, and neuroinflammation in specific populations (1–4,7).

This does not imply that all mood disorders are caused by mitochondrial dysfunction. Rather, impaired cellular energy production may represent an under-recognised contributing factor in complex, chronic, or treatment-resistant cases.

Neurotransmitter synthesis, release, and reuptake are all energy-dependent processes. When ATP availability is reduced, neurotransmitter signalling may become inefficient—even when neurotransmitter levels appear adequate on standard assessment (3,8).

Why Conventional Mental Health Care May Miss This

Standard mental health assessment appropriately focuses on psychological history, symptom patterns, and—where indicated—pharmacological modulation of neurotransmitters. This approach is effective and essential for many individuals.

However, routine mental health care rarely evaluates cellular energy metabolism, oxidative stress, or mitochondrial efficiency. Standard blood tests do not directly assess ATP production or metabolic bottlenecks that influence neuronal energy availability (5,9).

As a result, individuals experiencing overlapping symptoms—such as depression, chronic fatigue, exercise intolerance, or cognitive fog—may be told their results are “normal,” despite ongoing functional impairment. This reflects current testing limitations rather than a failure of care.

How Mitochondrial Dysfunction Can Influence Mental Health

When mitochondrial function is impaired, several downstream effects may occur:

• Reduced ATP production, limiting neuronal firing capacity and cognitive endurance (3,6)
• Increased oxidative stress, which can damage neuronal membranes and enzymes (7,8)
• Low-grade inflammation, commonly associated with altered mood and motivation (4,10)
• Impaired detoxification and metabolic clearance, contributing to cognitive fog (9)
• Disrupted synthesis of key neurotransmitters, including serotonin and dopamine (3,8)

These mechanisms have been observed in subsets of individuals with depression, bipolar disorder, chronic fatigue syndrome, and neurodegenerative conditions, although the degree of involvement varies between individuals (1–3,9,11).

Why Antidepressants May Help Some People — and Not Others

Antidepressant medications can be effective and appropriate, particularly in moderate to severe depression. However, response rates vary, and a significant proportion of individuals experience only partial or minimal benefit (15).

Emerging research suggests that altered energy metabolism and inflammatory signalling may limit the brain’s capacity to utilise neurotransmitters efficiently, even when their availability is pharmacologically increased (1,3,4).

This does not invalidate antidepressant therapy. Instead, it highlights that additional physiological contributors may need to be addressed in some individuals alongside standard mental health care.

Solution Explained: A Functional, Systems-Based Assessment

At Elemental Health and Nutrition, mitochondrial health is assessed indirectly using pattern-based functional testing rather than a single diagnostic marker. This approach is led by Rohan Smith, Functional Medicine Practitioner with over 12 years of clinical experience.

Assessment may include:

• Organic acids testing to evaluate metabolic intermediates related to mitochondrial pathways, oxidative stress, and nutrient sufficiency (9)
• Functional blood chemistry assessing thyroid, liver, glucose regulation, iron status, and inflammatory markers that influence energy metabolism
• Comprehensive gut testing, recognising that gut-derived inflammation and nutrient malabsorption can impair mitochondrial performance (10)
• Environmental exposure assessment, as certain toxins are recognised mitochondrial inhibitors (5)

These tools are used to identify contributing patterns and physiological stressors. They do not diagnose psychiatric conditions and are intended to complement—not replace—psychological or psychiatric care.

When to Consider a Mitochondrial Contribution

A mitochondrial component may be worth exploring when low mood or anxiety occurs alongside:

• Chronic or unexplained fatigue
• Post-exertional exhaustion
• Brain fog or cognitive slowing
• Reduced stress tolerance
• Multiple nutrient deficiencies
• Limited or short-lived response to standard treatments

Not all individuals will exhibit a mitochondrial contribution, and careful, individualised assessment is required.

Key Insights

• The brain is one of the body’s most energy-dependent organs (6)
• Impaired mitochondrial function may contribute to mood and cognitive symptoms in some individuals (1–4)
• Standard testing does not typically assess cellular energy metabolism
• A systems-based approach can help identify overlooked contributors
• Addressing physiology complements—rather than replaces—psychological care

Next Steps

If persistent fatigue, brain fog, or low mood have not responded as expected to conventional approaches, a deeper evaluation may be appropriate.

Discovery calls are available to review symptom patterns, relevant history, and potential next steps in an exploratory, evidence-informed, and individualised manner.

👉 Learn more about our functional approach to mental health

References

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