TED Series, Part V: Vitamin C and Mental Health: Neurotransmitters, Stress, and Emotional Resilience

Daniel Mirea (October 2025)
NeuroAffective-CBTยฎ | https://neuroaffectivecbt.com


Abstract

In this fifth instalment of TED (Tiredโ€“Exerciseโ€“Diet) series, of the NeuroAffective-CBTยฎ project, we explore the multifaceted role of Vitamin C in mental health. Emerging evidence suggests optimal neurocognitive benefits occur at daily intakes of 200โ€“500 mg. Beyond its reputation as an immune booster, Vitamin C functions as a key modulator of neurotransmitter synthesis, oxidative stress, and immuneโ€“brain communication. Drawing on recent research in neuroscience, nutritional psychiatry, and psychoneuroimmunology, this article examines how Vitamin C supports emotional regulation, cognitive performance, and resilience under chronic stress. Integrating this evidence within the NeuroAffective-CBTยฎ (NA-CBT) framework, we highlight Vitamin C as a practical component of lifestyle-oriented psychotherapy, bridging nutrition, physiology, and affect regulation.


Introducing TED in the NeuroAffective-CBTยฎ Framework

The TED model (Tiredโ€“Exerciseโ€“Diet) synthesises neuroscience, psychophysiology, and behavioural science into an integrated scaffold for emotional regulation and biological stability. Within NeuroAffective-CBTยฎ, TED interventions are introduced early in therapy to restore homeostasis across the Bodyโ€“Brainโ€“Affect triangle, the physiological foundation of affective regulation, motivation, and self-concept (Mirea, 2023; Mirea, 2025).

Following earlier TED instalments on Creatine (Part I), Insulin Resistance (Part II), Omega-3 (Part III), and Magnesium (Part IV), this chapter focuses on Vitamin C, a micronutrient that bridges diet, stress, immunity, and cognition. Despite being essential to brain and body function, humans have lost the genetic capacity to synthesise Vitamin C, making dietary intake or supplementation critical for maintaining mental and metabolic health.


Evolutionary Context: A Necessary Deficiency

Unlike most mammals, humans lack the gulonolactone oxidase gene required for endogenous Vitamin C synthesis. Evolutionarily, this was likely pruned due to ancestral diets rich in fruits and vegetation (Harrison & May, 2009). Consequently, Vitamin C must be obtained through food, primarily fruits, vegetables, and, more recently, supplementation.

This evolutionary dependency aligns with human dietary anatomy: our dentition and digestive tract are optimised for plant-based, nutrient-dense foods rather than raw animal flesh. Thus, our reliance on Vitamin C-rich diets is biologically hardwired, linking nutrition directly to both immune and psychological resilience.

From a TED perspective, this represents a fundamental Dietโ€“Affect relationship: emotional and physiological stability rely on the consistent intake of nutrients we cannot make ourselves.


Vitamin C and Neurotransmitter Synthesis

Vitamin C plays a pivotal biochemical role in neurotransmitter regulation. It acts as a cofactor for dopamine ฮฒ-hydroxylase, the enzyme converting dopamine into norepinephrine (adrenaline), essential for motivation, attention, and stress response (Otte et al., 2016). It is also necessary for the metabolism of tryptophan into serotonin, the neurotransmitter most associated with emotional regulation and well-being (Young, 2020).

Low Vitamin C levels have been linked to reduced serotonin and norepinephrine activity, contributing to low mood, fatigue, and anxiety. In turn, adequate Vitamin C enhances the synthesis and stability of these neurotransmitters, improving energy and affective balance.

๐Ÿ’ก TED Translation:
Vitamin C acts as a โ€œbiochemical connectorโ€ in the Tired and Diet domains, fuelling the brainโ€™s ability to convert nutrients into emotion-regulating signals. When Vitamin C is low, dopamine and serotonin pathways slow down, leading to fatigue, irritability, and low resilience under stress.


Stress, Cortisol, and Oxidative Load

Vitamin C is among the most concentrated antioxidants in the brain and adrenal glands, the latter being the bodyโ€™s cortisol-producing centres. Chronic psychological or physical stress depletes Vitamin C rapidly, while low Vitamin C status impairs the bodyโ€™s ability to modulate cortisol output (Brody et al., 2002).

Experimental studies show that supplementation can reduce stress-induced cortisol elevations and improve mood under high-pressure conditions, such as academic or occupational stress (de Oliveira et al., 2015). The relationship is reciprocal: stress depletes Vitamin C, and deficiency heightens the physiological stress response.

๐Ÿ’ก TED Translation:
This is where Tired meets Diet: stress โ€œburns throughโ€ Vitamin C reserves, and depletion feeds back into higher cortisol and anxiety. Maintaining adequate Vitamin C helps keep the stress response efficient rather than overreactive.


Vitamin C, Immunity, and the Gutโ€“Brain Axis

Vitamin C supports both innate and adaptive immunity, promoting leukocyte function, barrier integrity, and antioxidant defence (Carr & Maggini, 2017). Its influence extends to the gutโ€“brain axis, the bidirectional communication between intestinal microbiota and the central nervous system.

Figure 1: The Vitamin Cโ€“Neurotransmitterโ€“Stress Interaction Loop

Deficiency in Vitamin C increases intestinal permeability (โ€œleaky gutโ€) and systemic inflammation, which can trigger neuroinflammatory cascades linked to depression and anxiety (Otte et al., 2016). Adequate Vitamin C intake may therefore modulate mood indirectly by maintaining gut integrity and reducing inflammatory load.

๐Ÿ’ก TED Translation:
Within TED, Vitamin C stabilises both the body and the mind, supporting the โ€œDietโ€ domain by maintaining gut health and the โ€œAffectโ€ domain by reducing the inflammatory signals that disrupt mood regulation.


Epigenetic and Cognitive Dimensions

Emerging research suggests Vitamin C contributes to epigenetic regulation, influencing DNA methylation and histone modification processes involved in early neurodevelopment and long-term emotional outcomes (de Beni et al., 2021).

High concentrations of Vitamin C are found in the brain and cerebrospinal fluid, particularly in the hippocampus and cortex, regions essential for memory and emotional learning. Even when blood levels fall, the brain retains Vitamin C preferentially, highlighting its role in preserving neurocognitive function under stress.

๐Ÿ’กTED takeaway:

Your brain treats Vitamin C like gold, it holds onto it even when the rest of your body runs low. Thatโ€™s because Vitamin C helps protect brain cells, supports memory, and keeps emotional circuits flexible under stress. New research shows that Vitamin C doesnโ€™t just work in the moment, it may even influence how certain genes involved in brain development and emotional balance get โ€œswitched onโ€ or โ€œoff.โ€ In simple terms, Vitamin C helps your brain stay adaptable, protecting your mood and mental sharpness over time. In TED language, vitamin C fuels both Diet and Affect, nourishing your brainโ€™s chemistry while helping it handle lifeโ€™s stress without burning out.


Clinical and TED Practical Guidance

Recommended dietary intake for adults is 75โ€“90 mg/day, but emerging data suggest higher doses (200โ€“500 mg/day) may optimise antioxidant and neurochemical benefits (Carr & Rowe, 2020).

Natural sources:

  • Citrus fruits (orange, lemon, grapefruit)
  • Kiwi, strawberries, papaya
  • Bell peppers, broccoli, spinach, kale

Supplementation:

  • Divide doses (e.g., 250 mg twice daily) for better absorption.
  • Combine with flavonoid-rich foods (e.g., berries, green tea) to enhance bioavailability.
  • Avoid smoking and chronic alcohol use, which accelerate Vitamin C depletion.

๐Ÿ’กTED Translation:
Think of Vitamin C as your brainโ€™s โ€œdaily maintenance nutrientโ€, keeping neurotransmitters balanced, inflammation low, and energy steady. Consistent intake, alongside sleep and exercise regulation, reinforces the biological base for emotional stability and therapeutic progress. This is such a vital hormone, clinicians may consider psychoeducating clients on Vitamin Cโ€™s stress-buffering role when addressing fatigue or anxiety, integrating nutritional discussions within TED-based behavioural activation plans.


Summary & Outlook

Vitamin C exemplifies the TED principle that emotional health begins with biological balance. It supports neurotransmitter synthesis, moderates stress responses, protects against oxidative damage, and sustains gut and immune integrity. Within NeuroAffective-CBTยฎ, Vitamin C functions as both a preventive and adjunctive intervention, enhancing emotional resilience and amplifying the effects of psychotherapeutic change.

Like Omega-3, Magnesium, and Creatine in earlier TED modules, Vitamin C represents a key neuro-metabolic pathway where diet and mood converge. However, supplementation should never replace clinical care, it must be introduced under professional guidance and viewed as a supportive component of comprehensive mental health treatment.

Emerging evidence suggests that optimal neurocognitive benefits occur at daily intakes of 200โ€“500 mg of slow release (or time release) Vitamin C, the type that stays longer in the system. Future research should explore Vitamin C supplementation within structured TED protocols for mood, stress, and cognitive disorders, bridging nutritional neuroscience with applied behavioural interventions.


โš ๏ธ Disclaimer

These articles are for educational purposes only and do not replace medical or psychological evaluation. Individuals should consult their GP or prescribing clinician before starting supplementation, especially if taking psychiatric or cardiovascular medication.


Series context: Mirea, D. (2025) TED Series, Part IV: Magnesium and Mental Health. NeuroAffective-CBTยฎ. Available at: https://neuroaffectivecbt.com/2025/10/21/ted-series-part-iv-magnesium-and-mental-health/ [Accessed 22 October 2025].

References

Brody, S., Preut, R., Schommer, K. and Schรผrmeyer, T. (2002) โ€˜Vitamin C high-dose supplementation reduces anxiety and cortisol levelsโ€™, Psychopharmacology, 159(3), pp. 319โ€“324.

Carr, A.C. and Maggini, S. (2017) โ€˜Vitamin C and immune functionโ€™, Nutrients, 9(11), 1211.

Carr, A.C. and Rowe, S. (2020) โ€˜The emerging role of vitamin C in health and diseaseโ€™, Nutrients, 12(9), 2736.

de Beni, R. et al. (2021) โ€˜Vitamin C and epigenetic regulation of brain development and functionโ€™, Frontiers in Neuroscience, 15, 690341.

de Oliveira, I.J. et al. (2015) โ€˜Effects of oral vitamin C supplementation on anxiety in students: A double-blind, randomized, placebo-controlled trialโ€™, Pak J Biol Sci, 18(1), pp. 11โ€“18.

Harrison, F.E. and May, J.M. (2009) โ€˜Vitamin C function in the brain: vital role of the ascorbate transporter SVCT2โ€™, Free Radical Biology and Medicine, 46(6), pp. 719โ€“730.

Mirea, D. (2023) Tired, Exercise and Diet Your Way Out of Trouble (TED Model). NeuroAffective-CBTยฎ. ResearchGate.

Mirea, D. (2025) TED Series, Part IV: Magnesium and Mental Health. NeuroAffective-CBTยฎ. Available at: https://neuroaffectivecbt.com/2025/10/21/ted-series-part-iv-magnesium-and-mental-health/ [Accessed 22 October 2025].

Otte, C., Gold, S.M., Penninx, B.W. et al. (2016) โ€˜Major depressive disorderโ€™, Nature Reviews Disease Primers, 2, 16065.

Young, S.N. (2020) โ€˜Tryptophan metabolism and serotonin synthesis: relevance for psychiatric disordersโ€™, Journal of Psychiatry & Neuroscience, 45(3), pp. 151โ€“161.

TED Series, Part IV: Magnesium and Mental Health – New Research Findings and NeuroAffective-CBTยฎ Implications.


Daniel Mirea (October 2025)
NeuroAffective-CBTยฎ | https://neuroaffectivecbt.com


Abstract

In this fourth instalment of the TED (Tiredโ€“Exerciseโ€“Diet) Series, we explore magnesium, an essential mineral often overlooked in discussions of mood, stress, and emotional regulation. Drawing from neuroscience, nutritional psychiatry, and the NeuroAffective-CBTยฎ framework, this article examines how magnesium supports brain function, sleep, and affective stability. It highlights evidence linking low magnesium levels to stress sensitivity, anxiety, and depression, and outlines how restoring magnesium balance may enhance emotional resilience, cognitive clarity, and therapeutic responsiveness.


Introducing TED in the NeuroAffective-CBTยฎ Framework

The TED (Tiredโ€“Exerciseโ€“Diet) model integrates neuroscience, psychophysiology, and behavioural science to restore balance across the Bodyโ€“Brainโ€“Affect triangle central to emotional health. Within NeuroAffective-CBTยฎ, TED interventions target the biological underpinnings of affective instability, fatigue, sleep disruption, poor diet, and chronic stress (Mirea, 2023; Mirea, 2025).

Following earlier TED instalments on Creatine (Part I), Insulin Resistance (Part II), and Omega-3 Fatty Acids (Part III), part IV turns to Magnesium, the quiet stabiliser of the nervous system. Though often overlooked, magnesium deficiency is widespread and increasingly recognised as a modifiable factor in stress, anxiety, and mood disorders. Despite its importance, subclinical magnesium deficiency affects an estimated 60โ€“70% of adults, with even higher rates observed in those under chronic stress or psychological strain (Maguire, 2018).


Magnesium and the Stress Response

Both physical and emotional stress, common in our multi-tasking, always-connected society, rapidly drain the bodyโ€™s magnesium stores. Research shows an inverse relationship between cortisol and magnesium levels: the higher the magnesium, the lower the cortisol (Takase et al., 2004). In turn, chronic stress accelerates magnesium loss through the urine and cellular loss, a process that weakens the bodyโ€™s ability to recover, creating a self-perpetuating loop of tension, fatigue, and anxiety.

In controlled studies, adrenaline infusions have been shown to rapidly and persistently reduce serum magnesium, with levels remaining low even after stress hormones subside (White et al., 1992). Observational data echo this: students under exam stress and soldiers anticipating conflict both show sharp declines in magnesium concentrations, particularly in red blood cells (Takase et al., 2004).

Environmental and sensory stressors such as noise exposure also increase magnesium loss through urine, lasting up to 48 hours post-exposure, suggesting that both psychological and physical stressors drain the same metabolic reserve.

TED translation: This is where Tired meets Diet, stress burns through magnesium, and low magnesium magnifies stress sensitivity, forming a self-perpetuating loop of fatigue and emotional tension.


Mechanisms: How Stress and Sleep Deplete Magnesium

During acute stress, the fight-or-flight response mobilises magnesium from cells into the bloodstream to support energy production and neuromuscular activity. However, prolonged or repeated stress leads to excretion rather than recycling, gradually lowering the bodyโ€™s magnesium reservoir.

Cortisol intensifies this cycle by stimulating the kidneys to excrete more magnesium, while inflammatory stress hormones further impair intestinal absorption. Over time, this results in lower intracellular magnesium in tissues such as muscle, brain, and heart, correlating with symptoms of tension, irritability, and restlessness.

Chronic sleep loss compounds the problem. Both short-term and long-term sleep deprivation reduce red blood cell magnesium levels, impairing vascular flow and contributing to the โ€œwired but tiredโ€ pattern common in anxiety and burnout (Takase et al., 2004).

Magnesium and Mental Health: Depression, ADHD, and Brain Aging

Magnesium and Depression

Epidemiological data from the National Health and Nutrition Examination Survey (NHANES) show that adults with the lowest magnesium intake have significantly higher rates of depression, particularly younger adults (Jacka et al., 2009).

A 2019 meta-analysis of 11 studies found that people with the lowest magnesium consumption were 81% more likely to experience depression than those with the highest (Derom et al., 2019).

Mechanistically, magnesium supports serotonin function, reduces neuroinflammation, and stabilises the excitatoryโ€“inhibitory balance of the brain, aligning with TEDโ€™s goal of calming hyperaroused affective circuits.

Magnesium and ADHD

Around 90% of individuals with ADHD show suboptimal magnesium levels, which correlate with irritability, restlessness, and sleep issues. Supplementing magnesium glycinate (125โ€“300 mg/day) for 4โ€“6 weeks can reduce symptoms and may even ease stimulant-related side effects.

Magnesium, Cognition, and Brain Aging

Recent research using UK Biobank data (n = 6,000) found that individuals with higher dietary magnesium intake (~550 mg/day) had larger grey matter and hippocampal volumes than those consuming ~350 mg/day, roughly the RDA (Peterson et al., 2023). These structural differences may reflect slower brain aging, roughly equivalent to one year of preserved neural integrity.

Complementary studies link higher magnesium intake to a lower risk of dementia and mild cognitive impairment in older adults, especially women (Yary et al., 2016). Magnesiumโ€™s neuroprotective effects likely stem from reducing oxidative stress, enhancing synaptic plasticity, and maintaining mitochondrial efficiency.


Magnesium and Sleep Physiology

Magnesium supports the onset and maintenance of sleep by activating GABAergic pathways and regulating melatonin synthesis. Randomised trials and meta-analyses show mixed outcomes likely due to differences in baseline magnesium status among participants, but studies consistently find that deficient individuals experience improved sleep quality following supplementation (Abbasi et al., 2012).

TED translation: Magnesium supports Tired by enhancing sleep restoration, Exercise by improving muscle relaxation, and Diet by regulating the energyโ€“stress feedback loop that shapes mood and focus.


Forms, Absorption, and Co-Nutrients

Not all magnesium forms are equally effective:

  • Best absorbed: Magnesium glycinate, citrate, malate, and L-threonate.
  • Less effective: Magnesium oxide (low absorption, laxative effect).

Optimise absorption by:

  • Taking magnesium with meals that include healthy fats or carbohydrates.
  • Co-supplementing vitamin D3 and vitamin B6, which enhance uptake.
  • Using divided doses throughout the day.
  • Avoiding enteric-coated capsules that delay intestinal release.

Magnesium L-threonate, in particular, crosses the bloodโ€“brain barrier and supports learning, memory, and synaptic density (Slutsky et al., 2010).

โš–๏ธ Dosage and Clinical Application

Target symptomRecommended formTypical dosageNotes
General stress / anxietyMagnesium glycinate or citrate250โ€“400 mg/daySplit doses with meals
Sleep disturbanceMagnesium glycinate or citrate200โ€“300 mg before bedEnhances relaxation
ADHD (children/adolescents)Magnesium glycinate powder125โ€“300 mg/dayGentle, better tolerated
Cognitive performanceMagnesium L-threonate1โ€“2 g/day (elemental Mg โ‰ˆ 150 mg)Crosses bloodโ€“brain barrier

Therapeutic effects typically take 3โ€“4 weeks as intracellular magnesium levels gradually normalise.

๐Ÿ’ก TED Translation

In TED terms:

  • Tired: Magnesium restores cellular energy and supports sleep recovery.
  • Exercise: Adequate magnesium improves muscle performance, oxygen delivery, and recovery.
  • Diet: Replenishing magnesium reduces stress reactivity and emotional fatigue.

Together, these effects stabilise the Bodyโ€“Brainโ€“Affect system, preventing the physiological overload that fuels shame-based and affective dysregulation.


Summary & Outlook

Magnesium is a cornerstone of emotional and metabolic balance. Chronic stress, disrupted sleep, and processed diets have created widespread deficiency that quietly undermines mental health.

Evidence now supports magnesium as a low-cost, physiologically synergistic intervention for anxiety, ADHD, depression, and stress-related fatigue. Within the NeuroAffective-CBTยฎ framework, it complements psychotherapeutic change by restoring the biological foundations of calm, focus, and resilience. When combined with structured TED interventions, consistent sleep, regular movement, and nutrient-dense meals, magnesium reinforces the physiological stability needed for enduring psychological growth.

Future directions include evaluating magnesium supplementation within integrated TED protocols for mood and stress-related disorders, bridging nutritional neuroscience with applied cognitive-behavioural intervention research.


โš ๏ธ Disclaimer

These articles are for educational purposes and do not replace medical or psychological evaluation. Individuals should consult their GP or prescribing clinician before starting supplementation, particularly if taking psychiatric or cardiovascular medication.


Series context: Mirea, D. (2025) TED Series, Part III: Omega-3 and Mental Health. NeuroAffective-CBTยฎ. Available at: https://neuroaffectivecbt.com/2025/10/18/ted-series-part-iii-omega-3-and-mental-health/ [Accessed 21 Oct 2025].

References

Abbasi, B., Kimiagar, M., Sadeghniiat, K., Shirazi, M.M., Hedayati, M. & Rashidkhani, B. (2012). The effect of magnesium supplementation on primary insomnia in elderly subjects: A double-blind placebo-controlled clinical trial. Journal of Research in Medical Sciences, 17(12), 1161โ€“1169.

Derom, M.-L. et al. (2019). Magnesium and depression: A systematic review and meta-analysis. Nutrients, 11(11), 2473.

Freeman, M.P. et al. (2006). Omega-3 fatty acids: Evidence basis for treatment and future research in psychiatry. Journal of Clinical Psychiatry, 67(12), 1954โ€“1967.

Jacka, F.N. et al. (2009). Association between magnesium intake and depression in adults. Australian and New Zealand Journal of Psychiatry, 43(1), 45โ€“52.

Kirkland, A.E., Sarlo, G.L. & Holton, K.F. (2018). The role of magnesium in neurological disorders. Nutrients, 10(6), 730.

Maguire, M. C. (2018) Challenges in the Diagnosis of Magnesium Status. International Journal of Trace Elements in Medicine and Biology, 50, pp. 7-13. Available at: https://pubmed.ncbi.nlm.nih.gov/30200431/ [Accessed 21 Oct 2025].

Mirea, D. (2023) Tired, Exercise and Diet Your Way Out of Trouble (TED Model). NeuroAffective-CBTยฎ. Available at: https://neuroaffectivecbt.com [Accessed 21 October 2025].

Mirea, D. (2025) TED Series, Part III: Omega-3 and Mental Health. NeuroAffective-CBTยฎ. Available at: https://neuroaffectivecbt.com/2025/10/18/ted-series-part-iii-omega-3-and-mental-health/ [Accessed 21 October 2025].

Slutsky, I. et al. (2010). Enhancement of learning and memory by elevating brain magnesium. Neuron, 65(2), 165โ€“177.

Takase, B. et al. (2004). Influence of chronic stress and magnesium status on cardiovascular function and blood flow. Clinical Cardiology, 27(12), 671โ€“677.

White, J.R. et al. (1992) โ€˜Adrenaline infusion reduces plasma magnesium concentrations in humansโ€™, Clinical Science, 82(3), pp. 299โ€“303.

Yary, T. et al. (2016) โ€˜Dietary magnesium intake and the risk of dementia: A longitudinal cohort studyโ€™, European Journal of Nutrition, 55(6), pp. 2143โ€“2151.

TED Series, Part III: Omega-3 and Mental Health.

New Research Findings and NeuroAffective-CBTยฎ Implications

In this third instalment of the TED (Tiredโ€“Exerciseโ€“Diet) Series, we explore how omega-3 fatty acids, particularly EPA and DHA, influence mood, cognition, and emotional regulation. Drawing from neuroscience, nutritional psychiatry, and the NeuroAffective-CBTยฎ framework, this article examines the growing evidence that dietary fats do more than protect the heart, they also nourish the mind. Blending practical TED applications with current clinical research, it offers clinicians and readers accessible strategies for integrating omega-3s into a new lifestyle-based approach to mental health.

Introducing TED in the NeuroAffective-CBTยฎ Framework

The TED (Tiredโ€“Exerciseโ€“Diet) model brings neuroscience, nutritional psychiatry, psychophysiology, and behavioural science into an integrated framework for emotional regulation and mental health. Within the broader NeuroAffective-CBTยฎ (NA-CBT) programme, TED is introduced early to support self-regulation and biological stability, the โ€œBodyโ€“Brainโ€“Affectโ€ triangle that underpins shame-based and affective disorders (Mirea, 2023; Mirea, 2025).

Earlier parts of this series explored the roles of creatine and insulin regulation in mood and cognition. This third instalment turns to omega-3 fatty acids, essential nutrients that play a central role in brain health, mood regulation, and anti-inflammatory balance.


Why Omega-3s Matter: The Brainโ€™s Structural Fat

When people hear the word โ€œfat,โ€ they often think of storage fat the kind that accumulates around the waist or organs. But the brain depends on an entirely different type: structural fat, which makes up the cell membranes of neurons. These membranes control how signals and chemicals move between brain cells, and their flexibility directly affects how efficiently neurons communicate (Huberman, 2023).

Omega-3 fatty acids, primarily EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) are the building blocks of these membranes. DHA maintains the structure of neurons, while EPA modulates inflammation and neurotransmission, influencing serotonin and dopamine signalling (Freeman et al., 2006; Mocking et al., 2020).

From a TED perspective, this is where Diet meets Affect: better membrane health and lower inflammation translate into improved emotional regulation, resilience to stress, and more stable mood patterns.

๐Ÿงฌ What Are EPA and DHA? (In Simple Terms)

When we talk about omega-3 fatty acids, weโ€™re mostly referring to two main types that the body uses for brain and heart health:

  • EPA (Eicosapentaenoic Acid): Think of EPA as the firefighter in your system. It helps reduce inflammation, calm overactive stress responses, and balance the brainโ€™s chemical messengers that affect mood. Studies show that getting enough EPA can help lift low mood and reduce symptoms of depression.
  • DHA (Docosahexaenoic Acid): DHA is more like the architect of your brain. It builds and maintains the structure of your brain cells, especially in areas responsible for memory, focus, and emotional stability. Itโ€™s crucial for brain development, but also for keeping adult brains flexible and resilient under stress.

Both EPA and DHA work together , EPA helps your brain feel better, and DHA helps it work better. You can get them from oily fish like salmon, sardines, and mackerel, or from algal oil if you follow a plant-based diet.

๐Ÿ’ก TED Translation:
EPA supports the Diet part of TED by reducing emotional inflammation, those biochemical โ€œstormsโ€ that make you feel tense or flat. DHA supports the Tired part, helping your brain stay sharp and recover faster when youโ€™re mentally drained. Together, they strengthen the brainโ€“body connection that TED and NeuroAffective-CBTยฎ aim to restore. It is important to note that these supplements do not cure mental health conditions but can operate as adjuncts to therapy and medication, supporting recovery and prevention.


๐Ÿ”ฌ Evidence from Research: Depression, Focus, and Emotional Health

EPA and Depression – What Research Shows

A growing number of studies show that omega-3 supplements rich in EPA (about 1 gram per day) can noticeably reduce symptoms of depression. In some cases, the improvements are similar to those seen with common antidepressant medications in people with mild to moderate depression (Peet & Horrobin, 2002; Martins, 2009; Mocking et al., 2020).

One major study compared 1 gram of EPA to fluoxetine (Prozac), a widely used SSRI antidepressant and found that both worked equally well in improving mood. The group that combined EPA and fluoxetine together did even better, suggesting that omega-3s may enhance the effects of antidepressant treatment (Nemets et al., 2006).

Scientists believe EPA helps mood in several ways. It reduces inflammation in the body and brain (which can interfere with mood-regulating chemicals like serotonin) and keeps brain cell membranes flexible, allowing signals to travel more efficiently between neurons (Su et al., 2018).

๐Ÿ’ก TED Translation:
In TED terms, EPA acts like a โ€œmood stabiliserโ€ for the bodyโ€“brain system, calming internal inflammation, improving brain energy flow, and helping emotions move more smoothly through the day.

DHA and Cognition – The Brainโ€™s Structural Support

While EPA helps regulate mood and inflammation, DHA focuses more on the structure and performance of brain cells. Itโ€™s especially concentrated in brain areas responsible for memory, focus, and emotional balance, such as the prefrontal cortex and hippocampus.

Research shows that people who get enough DHA perform better on memory and attention tasks, particularly older adults or those who normally eat little fish or other omega-3 sources (Yurko-Mauro et al., 2010). DHA helps brain cells maintain flexible outer membranes, allowing them to communicate efficiently and adapt to new information, a process linked to learning and resilience.

When DHA levels are low, brain signalling can become sluggish, affecting concentration, motivation, and even emotional stability. Regular intake through food (like oily fish) or supplements can help restore this โ€œneural flexibility.โ€

๐Ÿ’ก TED Translation:
In TED language, DHA supports the Tired and Diet domains, it helps the brain stay sharp, focused, and emotionally steady, especially under mental fatigue or stress. Think of it as giving your neurons the healthy fat insulation they need to keep your thoughts and emotions running smoothly.


โš–๏ธ Dosage, Ratios, and Practical Guidance

Most research suggests that taking between 1,000 and 2,000 mg per day of omega-3 fatty acids, especially formulations higher in EPA, can noticeably improve mood, focus, and general wellbeing (Martins, 2009; Mocking et al., 2020). For depression and emotional balance, experts often recommend that EPA make up at least 60% of the total omega-3 blend.

You can get these healthy fats from both food and supplements:

  • ๐ŸŸ Natural sources: oily fish such as salmon, sardines, mackerel, and anchovies.
  • ๐ŸŒฑ Plant-based options: chia seeds, flaxseed, walnuts, and algal oil (a vegan source rich in DHA).
  • ๐Ÿ’Š Supplements: choose products that are molecularly distilled or third-party tested for purity and heavy-metal safety.

Because omega-3s are fat-soluble, they are best absorbed when taken with meals that include some healthy fat, such as avocado, eggs, or olive oil.

๐Ÿ’ก TED Translation:
Omega-3s are like the high-quality oil in your brainโ€™s engine, helping neurons glide, communicate, and self-repair. For best results, pair consistent intake with the other TED elements: regular sleep (Tired), sports (Exercise), and nutrient-dense meals (Diet).


TED Practical Layer: Combining Nutrition with Behaviour

The TED approach is about how we live, not just what we take. Omega-3s work best when integrated into daily habits that support absorption, brain function, and emotional balance.

Here are a few practical ways to make that happen:

  1. Take omega-3s with meals that contain healthy fats.
    These fats, like those from eggs, olive oil, or avocado, help your body absorb EPA and DHA more efficiently.
  2. Pair with regular movement.
    Exercise increases enzymes that help omega-3s get into brain cells (Dyall, 2014). Even short daily walks or light strength training enhance this process.
  3. Balance omega-6 intake.
    Many modern diets contain too much omega-6 (from seed oils and processed foods), which can block omega-3 benefits. Aim for a lower omega-6 to omega-3 ratio (around 3:1) to reduce inflammation and support mood regulation (Simopoulos, 2016).
  4. Track mood and focus.
    Keep a brief weekly log of your energy, sleep, and emotional stability. Over a month or two, most people notice more mental clarity and steadier mood.

๐Ÿ’ก TED Translation:
Small, consistent actions matter. Taking omega-3s in the morning, walking regularly, and eating real, unprocessed foods all work together to open up the bodyโ€“brainโ€“affect loop, the very system TED aims to strengthen.

TED and NeuroAffective-CBTยฎ Integration

In the NeuroAffective-CBTยฎ (NA-CBT) framework, the TED model (Tired, Exercise, Diet) bridges the gap between the mind and body. Omega-3 supplementation fits naturally within the Diet domain, but its effects ripple across all three.

Low omega-3 levels have been linked to mood dysregulation, impulsivity, and emotional reactivity โ€” all central features of the bodyโ€“brainโ€“affect triangle that NA-CBT helps regulate (Mirea, 2025). Supporting neuronal health through dietary means therefore complements core CBT processes such as emotional awareness, behavioural activation, and self-compassion.

For clinicians, this integration can be structured through a few evidence-informed steps:

  1. Screen for dietary insufficiency or inflammation markers (e.g., high omega-6 intake, poor diet quality).
  2. Psychoeducate clients on the bodyโ€“mind connection โ€” explain how stabilising the bodyโ€™s biochemistry supports cognitive flexibility.
  3. Encourage gradual habit stacking, introducing omega-3s alongside TED routines (sleep hygiene, consistent exercise).
  4. Monitor outcomes, tracking not just mood changes, but energy, focus, and emotional resilience.

๐Ÿ’ก TED Translation:
Think of omega-3s as emotional lubricants, subtle but powerful agents that help the brainโ€™s communication systems run smoothly, making it easier for CBT tools to โ€œclick.โ€ Combined with good sleep and movement, they form part of a whole-person therapy that builds physiological and psychological balance from the inside out.


Summary & Outlook

The evidence around omega-3 fatty acids, particularly EPA and DHA, continues to grow, positioning them as safe, low-cost, and biologically plausible adjuncts for improving mood, cognition, and emotional regulation. In depression, EPA-dominant formulations (~1 g/day) have demonstrated antidepressant effects comparable to SSRIs in mild-to-moderate cases (Nemets et al., 2006; Mocking et al., 2020). DHA, on the other hand, plays a structural and neuroprotective role, supporting long-term cognitive resilience.

From the TED viewpoint, omega-3s bridge physiology and psychology. They not only support neuronal efficiency but also improve the emotional flexibility required for therapeutic change โ€” embodying TEDโ€™s principle that lifestyle science and psychotherapy are most effective when integrated.

Within the TED (Tiredโ€“Exerciseโ€“Diet) framework, omega-3s exemplify how dietary micro-interventions can amplify psychotherapeutic outcomes. Combined with good sleep, consistent exercise, and emotional processing, the three TED pillars, they help restore the physiological stability necessary for deeper psychological change.

For clinicians, the takeaway is practical:

  • Screen for dietary quality and omega-3 intake early in assessment.
  • Encourage balanced omega-3 to omega-6 ratios.
  • Integrate nutritional strategies alongside CBT interventions.
  • Track progress using both subjective (mood, focus) and objective (diet logs) measures.

๐Ÿ’ก Final Thought (TED Translation):
Omega-3s donโ€™t just feed the body, they fuel the brain. When woven into the TED lifestyle and NeuroAffective-CBTยฎ framework, they help restore energy, sharpen thinking, and smooth the emotional landscape, supporting the long-term goal of mindโ€“body regulation.


โš ๏ธ Disclaimer

These articles do not replace medical or psychological assessment. Regular health checks, including blood lipid and inflammatory markers, are recommended. Always consult your GP or prescribing clinician before starting supplementation, particularly if taking psychiatric medication or anticoagulants.


๐Ÿงพ References

Allen, P.J., Dโ€™Anci, K.E. & Kanarek, R.B. (2024) โ€˜Creatine supplementation in depression: bioenergetic mechanisms and clinical prospectsโ€™, Neuroscience & Biobehavioral Reviews, 158, 105308.
Dyall, S.C. (2014) โ€˜Long-chain omega-3 fatty acids and the brain: A review of the independent and shared effects of EPA, DHA and ALAโ€™, Frontiers in Aging Neuroscience, 6, 52.
Freeman, M.P. et al. (2006) โ€˜Omega-3 fatty acids: Evidence basis for treatment and future research in psychiatryโ€™, Journal of Clinical Psychiatry, 67(12), pp. 1954โ€“1967.
Huberman, A. (2023) Food and Supplements for Mental Health. The Huberman Lab Podcast, Stanford University.
Martins, J.G. (2009) โ€˜EPA but not DHA appears to be responsible for the efficacy of omega-3 supplementation in depressionโ€™, Journal of Affective Disorders, 116(1โ€“2), pp. 137โ€“143.
Mirea, D. (2023) Tired, Exercise and Diet Your Way Out of Trouble (TED Model). NeuroAffective-CBTยฎ. ResearchGate.
Mirea, D. (2025) TED Series, Part III: Omega-3 and Mental Health. NeuroAffective-CBTยฎ. Available at: https://neuroaffectivecbt.com/2025/10/18/ted-series-part-iii-omega-3-and-mental-health/ [Accessed 18 October 2025].
Mocking, R.J.T. et al. (2020) โ€˜Meta-analysis and meta-regression of omega-3 polyunsaturated fatty acid supplementation for major depressive disorderโ€™, Translational Psychiatry, 10, 190.
Nemets, B., Stahl, Z. & Belmaker, R.H. (2006) โ€˜Addition of omega-3 fatty acid to maintenance medication treatment for recurrent unipolar depressive disorderโ€™, American Journal of Psychiatry, 163(6), pp. 1098โ€“1100.
Simopoulos, A.P. (2016) โ€˜An increase in the omega-6/omega-3 fatty acid ratio increases the risk for obesity and metabolic syndromeโ€™, Nutrients, 8(3), 128.
Su, K.P. et al. (2018) โ€˜Omega-3 fatty acids in major depressive disorder: A preliminary double-blind, placebo-controlled trialโ€™, European Neuropsychopharmacology, 28(4), pp. 502โ€“510.
Yurko-Mauro, K. et al. (2010) โ€˜Beneficial effects of docosahexaenoic acid on cognition in age-related cognitive declineโ€™, Alzheimerโ€™s & Dementia, 6(6), pp. 456โ€“464.

TED Series, Part II: Insulin Resistance and Mental Health

Introducing TED in the NeuroAffective-CBTยฎ Framework

The TED (Tired-Exercise-Diet) model is more than just theory. Daniel Mirea first introduced TED in NeuroAffective-CBTยฎ publications such as โ€œTired, Exercise and Diet Your Way Out of Troubleโ€, where it is presented as a core module within the NA-CBT schema linking body, brain, and affect (Mirea, 2023; Mirea, 2025).

Within the broader NeuroAffective-CBTยฎ programme, comprising of six modules, TED is embedded early, supporting psychotherapeutic work targeting chronic internalised shame, self-loathing, self-regulation, and affective vulnerabilities (Mirea, 2023). The underlying principle is that lifestyle modification can enhance and stabilise psychotherapeutic gains (Firth et al., 2020; Lopresti, 2019).

TED integrates insights from neuroscience (e.g., gutโ€“brain signalling, reward pathways), nutritional psychiatry, psychophysiology (e.g., sleep deprivation), and behavioural science (habit formation, conditioning). By framing these domains, sleep, movement, and diet, under one umbrella, TED provides clinicians and clients with a flexible, evidence-informed scaffold for lifestyle-oriented intervention.

If Part I of the TED series explored creatineโ€™s interface with brain energetics and mood (Candow et al., 2022; Allen et al., 2024), Part II turns to a more widespread metabolic challenge: insulin resistance. What are its links to mental health, and how might TEDโ€™s lifestyle levers help?


Insulin Resistance & Mental Health: Why It Matters

Epidemiology & Hidden Burden

The World Health Organization estimates over one billion people globally live with diabetes or prediabetes, conditions rooted in chronic insulin resistance. Though early stages may lack dramatic physical symptoms, substantial evidence ties insulin resistance to mood disturbances: irritability, poor sleep, low motivation, brain fog, diminished self-confidence, depression, and anxiety.

Clinically, many mental health practitioners begin treatment for depression or anxiety without ordering metabolic labs, thereby potentially missing a root driver. Treating symptoms without addressing underlying insulin dysregulation may limit long-term efficacy.

Dietary Drivers & Dopamine Links

Modern diets, usually rich in refined sugars, starches, and processed carbohydrates, easily produce repeated glucose spikes. These not only tax metabolic systems but elicit strong dopamine responses, reinforcing cravings and behaviours analogous to substance addiction (Smith & Robbins, 2020). Sugar โ€œaddictionโ€ is increasingly framed as a real phenomenon, with parallels to addictive substances in neurobiology and behaviour (Kempton et al., 2024).

Excess glucose that is not immediately utilised is stored as fat, contributing to chronic inflammation, glycation (a form of molecular โ€œagingโ€), and metabolic stress. Over time, these processes damage organs, accelerate aging, and intersect with psychiatric vulnerability.

Mechanistic Cascade: From Glucose Spikes to Neural Dysregulation

When glucose surges, the pancreas secretes insulin to clear it from the bloodstream into liver, muscle, and fat tissue. In insulin resistance, muscle and liver cells become less responsive, so insulin must work harder. Over time, insulinโ€™s compensatory drive fails, and fat accumulation acceleratesโ€”especially visceral adiposity. Because skeletal muscle has high metabolic demand, individuals who train or have greater lean mass may buffer this process somewhat, but they are not immune.

In insulin resistance, cells degrade signalling pathways. One key culprit is diacylglycerol (DAG): metabolic overflow in muscle and liver leads to DAG accumulation, which impairs insulin receptor signalling (Schulman et al., 2019). Imagine an insulin โ€œkeyโ€ (insulin molecule) trying to unlock a blocked โ€œcar doorโ€ (GLUT4 transporter) but the signal pathway is jammed by DAG sludge.

From a TED viewpoint, knowingly or unknowingly, many people live in this metabolic state: they feel fatigue or fogginess after meals, gain โ€œstubbornโ€ fat, crave sweets, and feel stuck. Their cells are refusing insulinโ€™s โ€œkey,โ€ causing chronic internal stress that can manifest in mood, cognition, and energy dysregulation.

Prevalence & Clinical Relevance

In a striking study of 18 to 44-year-olds, 44.8 % were estimated to have insulin resistance; notably, half of them were not obese, demonstrating the โ€œthin-outside, fat-insideโ€ phenotype. That means many lean individuals may silently carry metabolic dysfunction. Importantly, several studies suggest insulin resistance is a stronger predictor of cardiovascular disease than LDL cholesterol (Reaven, 2011; Wang et al., 2022).

As insulin resistance worsens, elevated glycation, oxidative stress, inflammatory markers, and microvascular dysfunction set in. In the brain, these intersect with neuroinflammation, microglial activation, and compromised mitochondrial function, pathways implicated in depression and cognitive decline (Morris et al., 2017; Louie et al., 2023).


Intervention Levers: What TED Can Do (and What the Research Suggests)

Below is a revised structure of actionable insights, rooted in emerging metabolic neuroscience, that align well with the TED domains.

1. Postprandial Movement: The Manual โ€œTesla Doorโ€ Activation

A 10 to 20 minute walk after meals activates AMPK signalling. Adenosine monophosphate-activated protein kinase โ€“ an enzyme that helps your body use energy more efficiently and draw sugar from the blood into muscles, thus allowing glucose to enter muscle cells independently of insulin. In this metaphor, walking acts as a manual opener of the automatic Tesla door, granting access when the remote control (or the insulin) fails. This simple, low-risk strategy is well supported by metabolic research (Hawley & Holloszy, 2009; Richter & Hargreaves, 2013).

2. Carbohydrate Timing & Contextual Use

Use fast-digesting carbohydrates selectively (e.g. white rice or ripe bananas) during periods of high energy demand, such as intra-workout or immediately post-exercise, when insulin sensitivity is highest. This ensures glucose is directed into active muscle tissue rather than exacerbating systemic dysregulation. In other words, this refers to rare, strategic use in small amounts, only when the body can efficiently utilise glucose for fuel.

Two good examples of fast-digesting carbohydrates, often called high-glycaemic index carbs, are:

  1. White rice โ€“ breaks down quickly into glucose, providing a rapid spike in blood sugar and energy.
  2. Bananas (ripe) โ€“ contain simple sugars like glucose and fructose that are quickly absorbed, making them ideal before or during exercise.

๐Ÿ‘‰ Other common examples include white bread, honey, dextrose, sports drinks, or small amounts of fruit juice. This guidance, however, does not apply to individuals on a strict weight-loss programme. In such cases, the goal is to reduce overall glucose exposure and promote fat metabolism, meaning fast-digesting carbohydrates are best avoided.

๐Ÿ‘‰Emerging evidence suggests that consuming a small amount of vinegar, around one teaspoon diluted in water, before a high-carbohydrate or sweet meal can help moderate postprandial (after-meal) glucose spikes by slowing gastric emptying and improving insulin sensitivity (Johnston et al., 2004; Mitrou et al., 2010). This simple intervention, often highlighted by metabolic educators such as โ€œJesse the Glucose Goddessโ€, aligns with the TED modelโ€™s focus on practical, low-cost strategies to stabilise energy and mood through metabolic regulation.

3. Rate-limiting Absorption: Protein + Soluble Fibre

By combining carbs with protein and soluble fibre (e.g. psyllium, chia, pectin), you slow the influx of glucose, turning a firehose into a gentle stream. This helps prevent peaks and DAG formation. This method is well supported in glycaemic control literature (Wolever et al., 2008; Jenkins et al., 2018).

๐Ÿฅฃ Example: Oatmeal Power Bowl

Carbohydrate: Rolled oats (complex carbs that digest steadily)

Protein: Greek yoghurt or a scoop of whey protein mixed in

Soluble fibre: Chia seeds or ground flaxseeds (both rich in soluble fibre)

Healthy fats (optional): A few almonds or a teaspoon of nut butter

Extras: Add sliced banana or berries for natural sweetness

๐Ÿฅ— Alternative savoury example

  • Carbohydrate: Quinoa or sweet potato
  • Protein: Grilled salmon, chicken, or tofu
  • Soluble fibre: Steamed vegetables (broccoli, carrots) + half an avocado or lentils

๐Ÿ’ก TED says: his combo reduces post-meal glucose peaks, supports satiety, and keeps insulin responses smooth, exactly what TED aims for.

4. Sludge Clearance & Mitochondrial Support

  • Trimethylglycine (TMG): May enhance methylation, support mitochondrial function, and assist in DAG clearance pathways (Ueland et al., 2019).
  • Cinnamon: Contains insulin mimetic compounds; small trials suggest improved glycaemic control and insulin sensitivity when used judiciously (Khan et al., 2003).
  • Carnosine: Serves as a buffer and antiglycation agent, intercepting reactive sugar moieties before they damage tissues (Hipkiss, 2009).

5. Master Reset: Intermittent Fasting / Time-Restricted Eating

Caloric restriction or “fasting” regimes although not always recommended if one suffers from high-blood pressure (e.g. 16:8, 24-h fasts) can however flip metabolic switches: lower insulin, upregulate autophagy (cellular cleanup), and reduce DAG accumulation. Animal and human studies show fasting improves insulin sensitivity, clears metabolic โ€œsludge,โ€ and supports mitochondrial health (Longo & Panda, 2016; de Cabo & Mattson, 2019).

6. Synergy of TED: Sleep, Exercise, Diet & Metabolic Hygiene

  • Sleep deprivation impairs insulin sensitivity and raises cortisol, further dysregulating glucose control (Spiegel et al., 1999).
  • Resistance and aerobic exercise enhance insulin receptivity and mitochondrial density (Hawley & Lessard, 2008).
  • Diet quality (minimally processed foods, low glycaemic load) is central to preventing glucose surges.

7. Gutโ€“Brain Signalling & Cravings

Emerging research identifies neuropod cells in the gut lining that respond to nutrients (e.g. glucose, amino acids) and send electrical signals to the brain, influencing cravings, reward, and hedonic experience (Kaelberer et al., 2020). This offers a mechanistic bridge: diet choices influence not only metabolism but โ€œwhat feels goodโ€ and how the brain interprets internal states.


Implications for Clinical Practice & Research

  • Incorporate full blood works and/or metabolic screening including fasting insulin, HbA1c, lipid profile, and inflammatory markers into the psychological assessment process to identify underlying metabolic dysfunctions that may contribute to fatigue, irritability, or mood instability. Recognise insulin resistance as a psychometabolic driver of fatigue, irritability, and depressive symptoms. Training implications for education providers.
  • Integrate TED-aligned behavioural tools post-meal walks, fibre pairing, fasting or other nutritional protocols early in therapy.
  • TED-based interventions (post-meal movement, dietary pacing, fibre, cyclical fasting) could be integrated early in therapy, personalised, and monitored.
  • Controlled clinical trials are needed:
    • Does metabolic correction improve mood/anxiety outcomes?
    • What is the interaction between metabolic change and CBT efficacy?
    • Can neuropod modulation mediate craving reduction?

Summary & Outlook

  • Insulin resistance is more than a metabolic disease, it likely contributes to mood dysregulation, fatigue, cravings, and cognitive dysfunction.
  • Within the TED lens, lifestyle levers (movement, meal pacing, fibre, fasting) offer promising adjuncts to psychotherapeutic work.
  • The gutโ€“brain axis, cellular signalling (e.g. DAG accumulation), and mitochondrial health form mechanistic bridges between metabolism and mental health.
  • Future work should test TED-driven metabolic interventions in clinical populations, ideally with objective biomarker endpoints (insulin, inflammatory markers, MRS imaging).

๐Ÿ’ŠBiochemical Terms with Plain-Language Clarifications

AMPK adenosine monophosphate-activated protein kinase (an enzyme that acts as the bodyโ€™s โ€œenergy switch,โ€ helping cells burn fuel efficiently and move sugar from the bloodstream into muscles)

GLUT4 glucose transporter type 4 – a โ€œdoorwayโ€ protein that opens to let glucose enter muscle and fat cells when activated by insulin or exercise

DAG diacylglycerol – a fat-like molecule that builds up inside cells and โ€œjamsโ€ insulin signals, making it harder for the body to use glucose properly

Autophagy – a natural โ€œcellular recyclingโ€ process where old or damaged cell parts are broken down and reused to keep cells healthy

Glycation – a chemical process where excess sugar sticks to proteins and tissues, accelerating ageing and inflammation)

Mitochondria – tiny โ€œpower stationsโ€ inside cells that turn food into usable energy and are essential for brain and muscle function)

Neuropod cells – specialised sensory cells in the gut lining that communicate directly with the brain via electrical signals, influencing hunger, cravings, and mood

Carnosine – a naturally occurring compound found in muscle and brain tissue that helps protect cells from sugar-related damage and oxidative stress

TMG (Trimethylglycine) – a compound derived from beets that supports liver and mitochondrial function, helping cells process fats and sugars more effectively

โš ๏ธDisclaimer

Important: This article is not a substitute for professional medical or psychological assessment and care. Regular health checks and blood tests with your GP or family physician are essential, including from adolescence onward given rising rates of metabolic conditions (e.g., pre-diabetes, diabetes). Where appropriate, seek guidance from qualified professionals such as a GP, psychiatrist, registered nurse or nutritionist, or indeed a NeuroAffective-CBTยฎ therapist, who can interpret your health data and support sustainable lifestyle changes. Supplements and behavioural strategies discussed here cannot and should not replace prescribed psychiatric or medical treatments; they function as potential adjuncts within a supervised care plan. Used responsibly, TED-aligned interventions may enhance wellbeing and resilience, but responses vary and should always be monitored by a healthcare professional.

๐ŸงพReferences

Allen, P.J., Dโ€™Anci, K.E. & Kanarek, R.B., 2024. Creatine supplementation in depression: bioenergetic mechanisms and clinical prospects. Neuroscience & Biobehavioral Reviews, 158, 105308. https://doi.org/10.1016/j.neubiorev.2024.105308

Candow, D.G., Forbes, S.C., Chiang, E., Farthing, J.P. & Johnson, P., 2022. Creatine supplementation and aging: physiological responses, safety, and potential benefits. Nutrients, 14(6), 1218. https://doi.org/10.3390/nu14061218

de Cabo, R. & Mattson, M.P., 2019. Effects of intermittent fasting on health, aging, and disease. New England Journal of Medicine, 381(26), 2541โ€“2551. https://doi.org/10.1056/NEJMra1905136

Firth, J. et al., 2020. A meta-review of lifestyle psychiatry: the role of exercise, smoking, diet and sleep in mental disorders. World Psychiatry, 19(3), 360โ€“380. https://doi.org/10.1002/wps.20773

Hawley, J.A. & Holloszy, J.O., 2009. Exercise: itโ€™s the real thing! Nutrition Reviews, 67(Suppl 2), S172โ€“S178. https://doi.org/10.1111/j.1753-4887.2009.00170.x

Hawley, J.A. & Lessard, S.J., 2008. Exercise training-induced improvements in insulin action. Acta Physiologica, 192(1), 127โ€“135. https://doi.org/10.1111/j.1748-1716.2007.01783.x

Hipkiss, A.R., 2009. Carnosine and its possible roles in nutrition and health. Advances in Food and Nutrition Research, 57, 87โ€“154. https://doi.org/10.1016/S1043-4526(09)57003-1

Jenkins, D.J.A. et al., 2018. Effects of high-fibre foods on glycaemic control. Lancet Diabetes & Endocrinology, 6(10), 794โ€“807. https://doi.org/10.1016/S2213-8587(18)30135-0

Johnston, C.S., Kim, C.M. & Buller, A.J., 2004. Vinegar improves insulin sensitivity to a high-carbohydrate meal in subjects with insulin resistance or type 2 diabetes. Diabetes Care, 27(1), pp.281โ€“282.

https://doi.org/10.2337/diacare.27.1.281Kaelberer, M.M. et al., 2020. Gut neuropod cells: sensory transducers that couple the gut to the brain. Cell, 182(4), 947โ€“949. https://doi.org/10.1016/j.cell.2020.07.035

Khan, A. et al., 2003. Cinnamon improves glucose and lipids of people with type 2 diabetes. Diabetes Care, 26(12), 3215โ€“3218. https://doi.org/10.2337/diacare.26.12.3215

Kempton, M.J., Fusar-Poli, P. & Allen, P., 2024. Neurobiology of food reward and addiction. Trends in Neurosciences, 47(2), 112โ€“126. https://doi.org/10.1016/j.tins.2023.11.003

Longo, V.D. & Panda, S., 2016. Fasting, circadian rhythms, and time-restricted feeding in healthy lifespan. Cell Metabolism, 23(6), 1048โ€“1059. https://doi.org/10.1016/j.cmet.2016.05.001

Lopresti, A.L., 2019. A review of lifestyle factors that contribute to important pathways in depression: diet, sleep and exercise. Journal of Affective Disorders, 256, 38โ€“44. https://doi.org/10.1016/j.jad.2019.05.066

Louie, A.M., Ramos-Loyo, J. & Ketter, T.A., 2023. Insulin resistance and depression: shared pathways and implications. Frontiers in Psychiatry, 14, 1123657. https://doi.org/10.3389/fpsyt.2023.1123657

Mirea, D., 2023. Tired, Exercise and Diet Your Way Out of Trouble (T.E.D.) model. NeuroAffective-CBTยฎ. Available at: https://www.researchgate.net/publication/382274002_Tired_Exercise_and_Diet_Your_Way_Out_of_Trouble_T_E_D_model_by_Mirea [Accessed 17 Oct 2025].

Mirea, D., 2025. Why your brain makes you crave certain foods (and how โ€œTEDโ€ can help you rewire itโ€ฆ). NeuroAffective-CBTยฎ, 17 September. Available at: https://neuroaffectivecbt.com/2025/09/17/why-your-brain-makes-you-crave-certain-foods/ [Accessed 17 Oct 2025].

Mitrou, P., Petsiou, E., Papakonstantinou, E., Maratou, E., Lambadiari, V., Dimitriadis, P. & Raptis, S.A., 2010. Vinegar consumption increases insulin-stimulated glucose uptake by the forearm muscle in humans with type 2 diabetes. European Journal of Clinical Nutrition, 64(8), pp.871โ€“877. https://doi.org/10.1038/ejcn.2010.102

Morris, G., Berk, M., Carvalho, A.F. et al., 2017. The role of mitochondria in mood disorders. Bipolar Disorders, 19(7), 577โ€“596. https://doi.org/10.1111/bdi.12534

Reaven, G.M., 2011. Insulin resistance: the link between obesity and cardiovascular disease. Medical Clinics of North America, 95(5), 875โ€“892. https://doi.org/10.1016/j.mcna.2011.06.002

Richter, E.A. & Hargreaves, M., 2013. Exercise, GLUT4, and skeletal muscle glucose uptake. Physiological Reviews, 93(3), 993โ€“1017. https://doi.org/10.1152/physrev.00038.2012

Schulman, G.I. et al., 2019. Diacylglycerol activation of PKCฮต mediates hepatic insulin resistance. Physiological Reviews, 99(2), 511โ€“536. https://doi.org/10.1152/physrev.00061.2017

Smith, D.G. & Robbins, T.W., 2020. The neurobiological basis of obesity and binge eating. Physiology & Behavior, 222, 112978. https://doi.org/10.1016/j.physbeh.2020.112978

Spiegel, K., Leproult, R. & Van Cauter, E., 1999. Impact of sleep debt on metabolic and endocrine function. Lancet, 354(9188), 1435โ€“1439. https://doi.org/10.1016/S0140-6736(99)01376-8

TED Series, Part I: Could Creatine Play an Important Role to Mental Health?

In this first instalment of the TED (Tired-Exercise-Diet) series, we will explore the intriguing possibility that creatine supplementation, long associated with sports performance, might also play a role in mental health, especially in disorders rooted in shame, self-hate, self-criticism, and general affect dysregulation.

Introducing TED in the NeuroAffective-CBTยฎ Framework – Mireaโ€™s Contribution

The TED model (Tired-Exercise-Diet) synthesises insights from neuroscience (e.g., gutโ€“brain signalling, reward pathways), nutritional psychiatry, psychophysiology (e.g., sleep deprivation), and behavioural science (habit formation, conditioning). By organising these findings into three core domains, sleep, exercise, and diet, TED provides an accessible, flexible, and evidence-informed structure for lifestyle-oriented intervention.

But TED is not just theoretical: it is publicly presented and described by Daniel Mirea in the NeuroAffective-CBTยฎ literature. Mireaโ€™s โ€œTired, Exercise and Diet Your Way Out of Troubleโ€ (TED model) is available via ResearchGate, Academia, and the NA-CBT site as a leaflet and white-paper introduction to emotional regulation through lifestyle (Mirea, 2023). In his description, the TED module is positioned centrally within the NA-CBT method, linking body, brain, and affect, the Bodyโ€“Brainโ€“Affect triangle (Mirea, 2025).

Within the larger NeuroAffective-CBTยฎ programme (comprising six modules), TED is introduced early, immediately after assessment and conceptualisation. NA-CBT specifically targets shame-based disorders such as self-loathing, self-disgust, and low self-esteem, which often underpin psychopathologies like major depressive disorder and anorexia (Mirea, 2023). Addressing lifestyle factors may augment traditional CBT approaches (Firth et al., 2020; Lopresti, 2019).

Empirical evidence shows that improving sleep, increasing physical activity, and enhancing diet quality yield synergistic benefits for emotional regulation, reduction of maladaptive cravings, and improvement of self-esteem (Kandola et al., 2019; Irwin, 2015).

For clinicians, TED offers a concrete tool: integrate lifestyle domains early, personalise interventions, and use TED to amplify CBT. For researchers, it highlights testable mechanisms and opportunities for controlled trials.

This first part focuses on a lesser-known nutritional agent now attracting neuroscientific attention: creatine, a compound with emerging evidence linking it to neuroenergetics and mental health (Candow et al., 2022; Allen et al., 2024).

Why Creatine? What the Evidence Suggests (and Doesnโ€™t..)

The Rationale: Bioenergetics, Oxidative Stress, and Brain Demand

Creatine helps the body make and recycle energy quickly. It acts like a backup battery for your cells, keeping them charged when energy demand is high. While we often think of creatine as something that helps muscles perform better, the brain also uses a huge amount of energy, about one-fifth of everything the body burns at rest.

In people experiencing depression or anxiety, studies suggest that the brainโ€™s mitochondria (the cellโ€™s โ€œpower stationsโ€ that turn food into usable energy) often donโ€™t work as efficiently. This can lead to higher levels of oxidative stressa kind of cellular โ€œwear and tearโ€ caused by unstable oxygen molecules that damage cells over time (Morris et al., 2017).

Taking creatine as a supplement may help the brainโ€™s mitochondria work more efficiently, reduce oxidative stress, and stabilise the brainโ€™s energy balance (Allen et al., 2024). Animal studies show that creatine can reduce stress in brain cells and even decrease depression-like behaviours (Zhang et al., 2023). Research in humans is still early, but the results so far are promising.


๐Ÿ’ก In simple TED terms:
Why Creatine Might Help the Brain: Energy and Stress Balance! Creatine may help the brain produce cleaner, steadier energy, while reducing the internal โ€œrustโ€ that builds up from stress and poor metabolism, both of which are key targets in emotional regulation.

Human Evidence: Mood, Cognition, and Stress Conditions

Mood and Depression

Early studies suggest that creatine may help boost the effects of antidepressant medication. In one carefully controlled trial, women who took 5 grams of creatine monohydrate per day alongside their usual SSRI antidepressant showed faster and stronger improvements in mood than those taking a placebo (Lyoo et al., 2012).

Several reviews of this research confirm that creatine seems most effective as an add-on rather than a stand-alone treatment (Allen et al., 2024; L-Kiaux et al., 2024). In other words, creatine may make existing treatments work better, but it is not yet proven to work on its own.

Although there have been no large human trials testing creatine by itself for depression or PTSD, brain-imaging studies show that creatine supplementation increases the brainโ€™s phosphocreatine levels (the stored form of cellular energy). This may help restore low brain-energy levels often found in people with mood disorders (Dechent et al., 1999; Rae & Brรถer, 2015).

๐Ÿ’ก TED translation: Creatine may act like an energy booster for the brain, helping antidepressants โ€œcatchโ€ faster and work more effectively. Within the TED framework, this fits the Diet domain, using nutrition to support energy stability and emotional regulation and, complements therapeutic work in the Affect domain.

Cognition, Memory, and Sleep Deprivation

Research also shows that creatine can help the brain think and react more effectively, especially when it is under pressure. Systematic reviews indicate that creatine can enhance memory, focus, and processing speed in conditions of metabolic stress, such as sleep deprivation, oxygen deprivation, or prolonged mental effort (Avgerinos et al., 2018; McMorris et al., 2017).

In one notable experiment, people who stayed awake all night performed better on reaction-time tasks and reported less mental fatigue after taking creatine (McMorris et al., 2006). These benefits appear strongest in older adults or individuals whose brains are already energy-challenged, for example, due to stress, ageing, or poor sleep (Dolan et al., 2018). In contrast, young, well-rested participants often show little or no change (Simpson & Rawson, 2021).

๐Ÿ’ก TED translation: Creatine seems to protect the brain when energy is low during exhaustion, stress, or lack of sleep. This is what we call a reactive emtional state (reactive amygdala). It doesnโ€™t make a healthy, rested brain โ€œsmarter,โ€ but it helps a tired brain function more efficiently. In TED terms, it bridges the Tired and Diet domains: improving sleep quality indirectly and supporting cognitive endurance under pressure.

Key Questions & Considerations

Dose, Duration, and Uptake

A few muscle studies, led by Dr. Darren Candow, show that taking 3โ€“5 grams of creatine monohydrate per day is enough to maintain muscle levels once stores are full. To load the system faster, some use about 20 grams per day for 5โ€“7 days, which quickly saturates muscle tissue (Candow et al., 2022; Kreider et al., 2017).

However, the brain takes longer to absorb creatine. Imaging studies suggest that at least 10 grams per day for several weeks may be needed to raise brain levels meaningfully (Dechent et al., 1999; Rae & Brรถer, 2015). Because around 95% of the bodyโ€™s creatine is stored in muscle, the brain receives its share more slowly, which may explain why mood or cognitive effects sometimes take weeks to appear.

๐Ÿ’ก TED translation: Creatine needs time to โ€œcharge the systemโ€. Like building savings in a bank, the longer and more consistently you invest, the better the returns. Within TED, this reflects the Tired and Diet domains, combining steady supplementation with sleep and nutrition for sustained brain energy.

Sodium and Electrolyte Co-Ingestion

Creatine is carried into cells by a sodium-chloride transporter (called SLC6A8) (Tachikawa et al., 2013). This means that electrolytes, especially sodium, help creatine get where it needs to go. While not yet proven for brain outcomes, pairing creatine with a small amount of electrolyte water or a balanced meal containing sodium may improve absorption.

๐Ÿ’ก TED translation: Think of sodium as a helper molecule, like a key that lets creatine into the cell. In TED language, this links Diet with Physiology: hydration, electrolytes, and nutrition work together to optimise energy flow.

Dietary Status

People who eat little or no animal protein, such as vegetarians or vegans, often start with lower creatine stores and therefore show a greater response to supplementation (Candow et al., 2022; Antonio et al., 2021). Interestingly, brain creatine levels appear to stay relatively stable across diet types, which suggests the brain has its own built-in regulation system (Rae & Brรถer, 2015).

๐Ÿ’ก TED translation: Your baseline diet changes how quickly you benefit from creatine. If you avoid animal foods, your muscles may โ€œfill upโ€ faster when you supplement but the brain keeps itself balanced. This reflects TEDโ€™s Diet principle: individualisation matters.

Safety and Misconceptions

Decades of studies confirm that creatine monohydrate is safe for healthy adults. No evidence links standard doses (3โ€“5 g/day) to kidney or liver problems (Kreider et al., 2017; Harvard Health Publishing, 2024). Increases in serum creatinine after supplementation simply reflect higher turnover, not kidney damage.

The often-mentioned hair-loss claim remains unsupported (Antonio et al., 2021). However, clinicians should note that in rare cases, individuals with bipolar disorder have reported manic switching after starting creatine (Silva et al., 2013). These cases are very uncommon but worth monitoring in sensitive populations.

๐Ÿ’ก TED translation: Creatine is one of the safest, best-studied supplements in both sport and health science. Still, as with all lifestyle tools, TED encourages personalisation and medical oversight, particularly in those with complex mental-health or metabolic conditions.

Implications for TED and NeuroAffective-CBTยฎ

In clinical settings, creatine can and should be viewed as a supportive tool rather than a replacement for established therapies. The goal is to use it thoughtfully in context, and always alongside medical supervision.

Practical guidelines:

  • Screen and personalise: Assess kidney function, diet, and medication interactions before supplementation.
  • Adjunctive use: Creatine should complement, not replace, therapy or pharmacological treatment.
  • Dosing: A short โ€œloadingโ€ phase of 20 g/day for 5โ€“7 days, or a gradual increase of 10โ€“20 g/day over four weeks, can be followed by 3โ€“5 g/day for maintenance (Candow et al., 2022).
  • Timing: Best used during periods of sleep loss, cognitive strain, or emotional exhaustion, when the brainโ€™s energy demands are high.
  • Integration: Combine with other TED domains, sleep hygiene, structured exercise, and nutrient-dense diet to amplify benefits (Firth et al., 2020).
  • Monitor and document: Track mood, focus, and physical function; adapt dosing empirically and contribute data to practice-based research.

๐Ÿ’ก TED translation: Creatine fits naturally within the Tiredโ€“Exerciseโ€“Diet framework as a metabolic support for emotional regulation. TED encourages clinicians to see it not as a โ€œpill for a problem,โ€ but as part of a whole-lifestyle system, where sleep, movement, and nutrition all reinforce psychological recovery.


Summary & Outlook

  • The TED model (sleep, exercise, diet) offers a practical bridge between psychotherapy and lifestyle science, especially for conditions rooted in shame, self-criticism, and affect dysregulation (Firth et al., 2020; Lopresti, 2019).
  • Creatine demonstrates strong scientific plausibility and early clinical promise for improving mood, cognition, and resilience under metabolic stress (Allen et al., 2024; Candow et al., 2022).
  • The next step for researchers is to conduct large, placebo-controlled clinical trials testing creatine as an adjunct to CBT for depression and anxiety โ€” ideally with neuroimaging to confirm its effects on brain energy metabolism.

๐Ÿ’ก TED translation: Creatine may one day become a recognised โ€œnutritional allyโ€ for the brain, enhancing therapy outcomes by helping clients feel less tired, more focused, and more emotionally stable. For now, it serves as a valuable prototype of how lifestyle science can empower both clinicians and clients to target emotional health from the body upward.

โš ๏ธ Disclaimer:
A final and important reminder: these articles are not intended to replace professional medical or psychological assessment and/or treatment. Regular blood tests and health check-ups with your GP or a private family doctor are essential throughout adult life, in fact increasingly relevant from adolescence onward, given the rising incidence of metabolic and endocrine conditions such as diabetes among young people. It is strongly recommended to seek guidance from qualified professionals, for example, a GP, clinical psychologist, a psychiatrist or depending on your personal goals and needs a registered nutritionist, indeed a NeuroAffective-CBTยฎ therapist, who can interpret your health data (including blood work) and help you understand how your lifestyle, daily habits, and nutritional choices influence your mental and emotional wellbeing.

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