Beyond the Traditional Mental Health Conversation

Beyond the Traditional Mental Health Conversation

By Justin Gregory Maguire

BSc (Hons) Nutritional Science.

PG Dip Functional Blood Chemistry Analysis.

BTech Kinesiology and Applied Anatomy

Many capable, high-functioning adults reach mid-life feeling as though they should be coping better than they are. On paper, life may appear successful. Yet internally, there may be fatigue, poor sleep, reduced motivation, brain fog, irritability, emotional flatness, or a sense that mental health recovery takes longer than it used to.

Mental health is multidimensional

Traditionally, mental health has often been discussed through mood, mindset, or neurotransmitters such as serotonin, dopamine, and norepinephrine. These remain important, and conventional treatments can be valuable. However, contemporary neuroscience suggests that mental well-being is rarely explained by one pathway alone. Depression and low resilience may reflect interactions between stress biology, inflammation, sleep, metabolism, neural plasticity, and large-scale brain network regulation (Herrman et al., 2022; Menon, 2011; Miller and Raison, 2016).

This broader view can be reassuring. It suggests that struggling with mental health is not caused by a lack of discipline, insight, or willpower. It may mean the systems that support regulation, recovery, motivation, and emotional flexibility are under strain.

For example, antidepressant medications often act through monoamine pathways. Yet, clinical improvement may involve slower downstream changes in receptor signalling, gene expression, synaptic plasticity, and brain network adaptation rather than neurotransmitter changes alone (Belmaker and Agam, 2008; Duman and Aghajanian, 2012). Similarly, chronic stress may influence cortisol patterns, immune signalling, hippocampal function, and emotional regulation, which explains why it can eventually affect mood, cognition, and energy (McEwen, 2017).

This view does not replace traditional care. Rather, it widens the conversation.

A more integrated approach would ask:

  • What might be making the brain and body less able to regulate, recover, and adapt?
  • Is sleep architecture disrupted?
  • Is inflammatory tone increased?
  • Is the nervous system overactivated?
  • Are metabolic or endocrine signals affecting energy and motivation?
  • Are lifestyle, relational, or environmental pressures reducing the brain’s capacity for plasticity?

Determine the correct support

The good news is that the brain remains adaptive. Research increasingly views psychological resilience as a dynamic process, influenced by biological, behavioural, and environmental inputs (Southwick et al., 2014). This means that meaningful support may come from several directions: medical care where appropriate, psychological support, sleep regulation, movement, nutritional foundations, stress recovery, social connection, and deeper physiological investigation when symptoms persist.

For readers who feel they have tried to ‘push through’ but still do not feel fully themselves, the next step may simply be to look more carefully at the wider system supporting mental well-being.

Autonomic Wellness offers a free provisional symptoms assessment to help guide this reflection. It is designed to highlight areas of physiology that may be worth considering when supporting mood, energy, cognition, stress tolerance, and recovery. Click on the link below for your free assessment:

Symptoms report

References

Belmaker, R.H. and Agam, G. (2008) Major depressive disorder. New England Journal of Medicine, 358(1), pp.55–68. Available from: https://doi.org/10.1056/NEJMra073096 [Accessed 20 March 2026].

Duman, R.S. and Aghajanian, G.K. (2012) Synaptic dysfunction in depression: potential therapeutic targets. Science, 338(6103), pp.68–72. Available from: https://doi.org/10.1126/science.1222939 [Accessed 20 March 2026].

Herrman, H., Patel, V., Kieling, C., Berk, M., Buchweitz, C., Cuijpers, P., Furukawa, T.A., Kessler, R.C., Kohrt, B.A., Maj, M. and McGorry, P. (2022) Time for united action on depression: a Lancet–World Psychiatric Association Commission. The Lancet, 399(10328), pp.957–1022. Available from: https://doi.org/10.1016/S0140-6736(21)02141-3 [Accessed 20 March 2026].

McEwen, B.S. (2017) Neurobiological and systemic effects of chronic stress. Chronic Stress, 1, p.2470547017692328. Available from: https://doi.org/10.1177/2470547017692328 [Accessed 20 March 2026].

Menon, V. (2011) Large-scale brain networks and psychopathology: a unifying triple network model. Trends in Cognitive Sciences, 15(10), pp.483–506. Available from: https://doi.org/10.1016/j.tics.2011.08.003 [Accessed 20 March 2026].

Miller, A.H. and Raison, C.L. (2016) The role of inflammation in depression: from evolutionary imperative to modern treatment target. Nature Reviews Immunology, 16(1), pp.22–34. Available from: https://doi.org/10.1038/nri.2015.5 [Accessed 20 March 2026]. Southwick, S.M., Bonanno, G.A., Masten, A.S., Panter-Brick, C. and Yehuda, R. (2014) Resilience definitions, theory, and challenges: interdisciplinary perspectives. European Journal of Psychotraumatology, 5(1), p.25338. Available from: https://doi.org/10.3402/ejpt.v5.25338 [Accessed 20 March 202

/0 Comments/by

When Recovery Does Not Fully Return:Long Covid, Depression, and the Hidden Community Care Gap

By Justin Gregory Maguire

BSc (Hons) Nutritional Science.

PG Dip Functional Blood Chemistry Analysis.

BTech Kinesiology and Applied Anatomy

Can long Covid cause depression?

Covid-19 is generally perceived as an infection that lasts for a period of a few days up to a few weeks. Yet for many people, recovery is not so simple. Long Covid has become an important health issue as symptoms can continue for many months after the initial infection. These symptoms may include exhaustion, breathlessness, brain fog, poor concentration, sleep disruption, and changes in mood. For some people, this ongoing state can begin to feel similar to depression, even though the original trigger is a viral illness rather than a primary mental health condition.

This matters because depression is one of the most significant health challenges worldwide. However, it is not a single, uniform illness. Depression can present differently from person to person, and it is often shaped by physical illness, social stress, economic hardship, and life circumstances (Herrman et al., 2022). This complexity makes it harder to define, diagnose, and treat consistently. The same problem now appears to be affecting long Covid care.

Getting the right care

A major concern raised in mental health research is the ‘treatment gap’. This refers to the large number of people who meet the criteria for depression yet never receive meaningful care. Across multiple countries, fewer than half of adults with depression have access to formal health services, and only around 10% receive care that can be considered truly effective (Thornicroft et al., 2017; Herrman et al., 2022). This is not only attributed to limited health services; it is also because symptoms are often misunderstood, dismissed, or poorly linked to the type of treatment that is required.

Long Covid seems to expose these same weaknesses in health systems. In South Africa, studies have shown that many people continue to experience symptoms for several months after infection. One large national cohort found that 66.7% of previously hospitalised adults still had persistent symptoms three months after discharge, with anxiety or depressive symptoms reported in roughly one-fifth of participants (Dryden et al., 2022). Another national cohort found that persistent symptoms remained present six months later in both hospitalised and non-hospitalised individuals, proving that long-term illness is not only limited to the severe acute cases (Jassat et al., 2023). In everyday language, this means that many people may ‘survive’ Covid yet not fully return to their previous level of physical, cognitive, or emotional functioning. A person may struggle to think clearly, feel constantly tired, or lose the sense of energy and motivation needed to work, socialise, or care for family. These inconveniences may seem minor but can adversely affect income, identity, independence, and mental well-being.

The importance of an accurate diagnosis

Comprehensive South African studies have shown that neuropsychiatric symptoms are common in long Covid. These symptoms can include depression, apathy, agitation, hallucinations or delusions, and insomnia – commonly found in patients with brain disease, injuries or dementia. In a Cape Town cohort, over half of participants experienced ongoing neuropsychiatric symptoms, while 44% were identified with objective cognitive impairment – which is a measurable diagnosis by a medical specialist (van Niekerk et al., 2025). Importantly, the biological markers measured early in illness did not consistently predict which patients would suffer long Covid. This creates a problem for frontline care: if there is no single test that clearly ‘proves’ long Covid, patients may be left in a grey zone where their suffering is real but difficult to precisely classify.

This diagnostic uncertainty is especially important in South Africa, where health systems are already under pressure. Long Covid symptoms can overlap with HIV, tuberculosis, anxiety, depression, and other chronic conditions (Pather, 2025). In busy clinics, where time and specialist support are limited, patients can easily fall through the cracks. Their symptoms may be treated as vague, non-specific, or secondary, rather than as part of a real and disabling post-viral condition.

Enhanced community awareness is required

Social realities make the problem worse. If someone is dealing with food insecurity, employment loss, transport costs, or limited access to healthcare, it becomes more difficult to get the correct care (Wickenden et al., 2023). In this context, long Covid is not only a medical issue. It also becomes a community issue, because optimum treatment for illness is mostly non-existent where there is poverty, disability, and fragmented public services.

Current South African policy recognises long Covid as a genuine condition and recommends symptom-led management within existing health services (Ministerial Advisory Committee on Covid-19, 2022). This is an important start, but recognition alone is not enough. Without clearer care pathways, better clinician awareness, and stronger links between medical, rehabilitation, and mental health support, many patients may continue to feel unseen.

Learnings from recent history

The encouraging part is that South Africa has dealt with complex chronic health challenges before. HIV care shows that outcomes can improve when support is decentralised into primary care, linked with community systems, and supported by trained non-specialist workers (Coetzee et al., 2004; Peltzer et al., 2012). Research on mental health has shown that practical psychosocial approaches such as psychoeducation, behavioural activation, and brief problem-solving support can be effective, especially in resource-constrained settings (World Health Organization, 2016; Chibanda et al., 2016).

The broader lesson is simple: people with long Covid-related, depression-like symptoms do not only need a label; they need joined-up care. That means care which sees fatigue, mood, cognition, and function as connected rather than separate. It also means building systems that do not require certainty before offering support.

The need for recognition of long Covid symptoms

Long Covid reminds us that recovery is not always visible, and that untreated distress is not necessarily caused by a lack of medicine. Sometimes it is caused by the gap between what people are living through and what health systems are prepared to recognise. Narrowing that gap may be one of the most important community tasks ahead to combat mental health and the link to long Covid.

References

Chibanda, D., Weiss, H.A., Verhey, R., Simms, V., Munjoma, R., Rusakaniko, S., Chingono, A., Munetsi, E., Bere, T., Manda, E. and Abas, M. (2016) Effect of a primary care–based psychological intervention on symptoms of common mental disorders in Zimbabwe: a randomized clinical trial. Jama, 316(24), pp.2618-2626. Available at: doi:10.1001/jama.2016.19102  

Coetzee, D., Boulle, A., Hildebrand, K., Asselman, V., Van Cutsem, G. and Goemaere, E. (2004) Promoting adherence to antiretroviral therapy: the experience from a primary care setting in Khayelitsha, South Africa. AIDS, 18, pp S27–S31. Available at: https://journals.lww.com/aidsonline/abstract/2004/06003/promoting_adherence_to_antiretroviral_therapy__the.6.aspx

Dryden, M., Mudara, C., Vika, C., Blumberg, L., Mayet, N., Cohen, C., Tempia, S., Parker, A., Nel, J., Perumal, R., Groome, M.J., Conradie, F., Ndjeka, N., Sigfrid, L., Merson, L. and Jassat, W. (2022) Post-Covid-19 condition 3 months after hospitalisation with SARS-CoV-2 in South Africa: a prospective cohort study. The Lancet Global Health, 10(9), pp.e1247–e1256. Available at: https://doi.org/10.1016/S2214-109X%2822%2900286-8

Herrman, H., Patel, V., Kieling, C., Berk, M., Buchweitz, C., Cuijpers, P., Furukawa, T.A., Kessler, R.C., Kohrt, B.A., Maj, M. and McGorry, P. (2022) Time for united action on depression: a Lancet–World Psychiatric Association Commission. The Lancet, 399(10328), pp.957–1022. Available at: https://doi.org/10.1016/S0140-6736%2821%2902141-3

Jassat, W., Mudara, C., Vika, C., Welch, R., Arendse, T., Dryden, M., Blumberg, L., Mayet, N., Tempia, S., Parker, A. and Nel, J. (2023) A cohort study of post-Covid-19 condition across the Beta, Delta, and Omicron waves in South Africa: 6-month follow-up of hospitalized and nonhospitalized participants. International Journal of Infectious Diseases, 128, pp.102–111. Available at: https://doi.org/10.1016/j.ijid.2022.12.036

Ministerial Advisory Committee on Covid-19 (2022) Diagnosis, treatment and management of long Covid. Pretoria: National Department of Health, South Africa. Available at: https://www.health.gov.za/wp-content/uploads/2024/09/MAC-Advisory-Memo_Diagnosis-Treatment-and-Management-of-Long-COVID-27-May-2022.pdf

Pather, K. (2025) Addressing Long COVID Challenges in South Africa’s District Health Clinics: A Scoping Review of Diagnostic Barriers and Care Integration. International Journal of Infectious Diseases, 152, 107483. Available at: https://doi.org/10.1016/j.ijid.2024.107483

Peltzer, K., Ramlagan, S., Jones, D., Weiss, S.M., Fomundam, H. and Chanetsa, L. (2012) Efficacy of a lay health worker led group antiretroviral medication adherence training among non-adherent HIV-positive patients in KwaZulu-Natal, South Africa: results from a randomized trial. SAHARA-J: Journal of Social Aspects of HIV/AIDS, 9(4), pp. 218–226. Available at: https://doi.org/10.1080/17290376.2012.745640

Thornicroft, G., Chatterji, S., Evans-Lacko, S., Gruber, M., Sampson, N., Aguilar-Gaxiola, S., Al-Hamzawi, A., Alonso, J., Andrade, L., Borges, G. and Bruffaerts, R. (2017) Undertreatment of people with major depressive disorder in 21 countries. The British Journal of Psychiatry, 210(2), pp.119–124. Available at: https://doi.org/10.1192/bjp.bp.116.188078

van Niekerk, I., Panieri, M., Müller, T., Mapahla, L., Dzanibe, S., Day, C., Stein, D.J. and Peter, J. (2025) Acute serum protein biomarker profile and prevalence of persistent (>6 months) neuropsychiatric symptoms in a cohort of SARS-CoV-2 PCR-positive patients in Cape Town, South Africa. Brain, Behavior, & Immunity – Health, 46, p.100990. Available at: https://doi.org/10.1016/j.bbih.2025.100990

Wickenden, M., Hart, T.G.B., Thompson, S.J., Davids, Y.D. and Ngungu, M. (2023) How did South Africans with disabilities experience COVID-19? Results of an online survey. African Journal of Disability, 12, p.1119. Available at: https://doi.org/10.4102/ajod.v12i0.1119

World Health Organization (2016) mhGAP Intervention Guide for Mental, Neurological and Substance Use Disorders in Non-Specialized Health Settings: Mental Health Gap Action Programme (mhGAP) World Health Organization. Available at: https://www.who.int/publications/i/item/9789241549790

/0 Comments/by

Misdirected Healing: Why Chasing Germs and Viral Flare-ups often Misses the Real Problem

By Justin Gregory Maguire

BSc (Hons) Nutritional Science.

PG Dip Functional Blood Chemistry Analysis.

BTech Kinesiology and Applied Anatomy

A different way of understanding chronic illness.

Many people living with long-term fatigue, inflammation, brain fog, autonomic instability, or repeated infections, are told a similar story:

  • ‘You still have an infection.’
  • ‘A virus has reactivated.’
  • ‘We need to eliminate another pathogen.’

Treatment often becomes a repeated effort to suppress bacteria, fungi, or viruses. While this may produce temporary improvement, symptoms frequently return.

This raises an important question:

What if recurring infections are not the primary problem, but a sign that the immune system has lost its ability to fully resolve danger?

This article presents a continuity model of chronic illness, where immune, metabolic, neurological, and environmental factors interact simultaneously. In this model, dysfunction is sustained by feedback loops – not by a single cause.

When recurring infections are a signal, not the source

Repeated extracellular pathogens (such as bacteria or fungi) and re-emergence of dormant viruses are often interpreted as the root cause of illness. However, in many chronic inflammatory states, these events appear because immune resolution is impaired, not because pathogens are unusually aggressive.

A healthy immune system does three things:

  • Attacks threats
  • Clears debris and dead cells
  • Signals when it is safe to stand down

When the clean-up and stand-down phases fail, microbes that are normally controlled can reappear. Treating them repeatedly may reduce symptoms, but it does not restore immune coordination.

The immune system stuck in ‘emergency mode’

The immune system operates in two broad modes:

  • Emergency mode – fast, inflammatory, aggressive
  • Resolution mode – clean-up, repair, and calming

In chronic illness, the system often becomes locked in emergency mode – a state sometimes described as autoinflammatory innate immune dysregulation.

When this occurs:

  •  Immune signalling becomes noisy
  •  Clean-up efficiency declines
  •  Regulatory receptors lose sensitivity

One of the most affected regulatory systems is the vitamin D receptor (VDR).

Why the vitamin D receptor matters

The vitamin D receptor functions as a central immune regulator. When responsive, it helps immune cells to:

  • Communicate effectively
  • Produce antimicrobial peptides
  • Limit excessive inflammation
  • Transition from attack to repair

In chronic inflammatory states, the VDR often becomes functionally resistant, even when blood vitamin D levels are normal or elevated. Reduced receptor sensitivity further impairs immune regulation, creating a self-reinforcing loop between inflammation and receptor dysfunction.

How impaired macrophage clean-up links spike protein to VDR dysfunction

Macrophages are immune cells responsible for:

  • Clearing dead or damaged cells
  • Removing inflammatory debris
  • Signalling immune resolution

Research has shown that when macrophages encounter dead cells containing viral material such as SARS-CoV-2 spike protein, their ability to complete clean-up (efferocytosis) becomes impaired (Salina et al., 2022). In parallel, spike-dependent opsonization has been shown to inhibit effective phagocytosis in a dose-dependent manner, further disrupting macrophage clearance capacity (Bahnan et al., 2022).

Furthermore, spike–antibody immune complexes may drive exaggerated inflammatory signalling in macrophages via Fc receptor engagement, thereby biasing these cells toward a pro-inflammatory phenotype rather than immune resolution (Hoepel et al., 2021).

Instead of resolving inflammation, these cells:

  • Remain in a pro-inflammatory state
  • Release excess inflammatory signals
  • Lose the ability to perform repeated clean-up cycles

Impact on the vitamin D receptor

Failed macrophage clean-up allows cellular debris and inflammatory signals to persist. This environment interferes with vitamin D receptor signalling, which requires relative intracellular stability to regulate immune genes effectively.

Spike protein does not directly deactivate the VDR. Rather, spike-associated macrophage dysfunction contributes to an inflammatory environment that undermines VDR responsiveness, reinforcing immune dysregulation.

Neutrophil overactivity, copper sequestration, and energy disruption

When macrophage resolution fails, neutrophils (PMN leukocytes) remain chronically active.

Prolonged neutrophil activity leads to functional copper sequestration, diverting copper away from normal cellular use. Copper is essential for:

  • Mitochondrial energy production
  • Antioxidant enzyme function
  • Immune balance

This redistribution does not necessarily reflect copper deficiency on blood tests, but rather impaired intracellular availability (Percival, 1998).

Cytochrome c oxidase, ATP loss, and danger signalling

Copper is required for cytochrome c oxidase, a key enzyme that maintains mitochondrial energy flow. When copper becomes functionally unavailable:

  • Mitochondrial stability weakens
  • Cytochrome c may be released prematurely
  • Cells shift into stress or death pathways

This leads to cellular ATP loss. When ATP escapes into the extracellular space, it acts as a danger signal, activating purinergic receptors and sustaining inflammation.

This creates a reinforcing loop:

Neutrophil overactivity → copper misallocation → mitochondrial stress → extracellular ATP → continued immune activation (Brown and Borutaite, 1999).

Copper reintroduction requires metabolic context

Simply adding copper can worsen oxidative stress if cellular systems are not prepared. Proper copper utilization depends on:

  • Sulfur metabolism
  • Antioxidant capacity
  • Glutathione preservation
  • Balanced methylation

Without these supports, copper may fail to enter cells effectively or increase oxidative burden (Uriu-Adams and Keen, 2005).

GHK-Cu: a regulated copper support strategy

GHK-Cu (glycyl-L-histidyl-L-lysine copper complex) represents a distinct approach to copper support.

Unlike free copper salts, GHK-Cu:

  • Preserves antioxidant balance
  • Helps preserve intracellular glutathione, rather than forcing recycling
  • May facilitate intracellular copper availability in a regulated manner
  • By supporting mitochondrial stability and cytochrome c oxidase function, it may indirectly reduce extracellular danger signalling (ATP release) through improved cellular resilience

GHK-Cu does not suppress inflammation directly. Instead, it supports cellular stability, reducing the conditions that generate danger signals in the first place (Pickart, 2008).

Potassium: why blood levels can be misleading

Most potassium in the body is stored inside cells, not in the bloodstream. As a result, serum potassium can appear normal even when intracellular potassium is depleted or poorly utilized.

Stress hormones, inflammation, acid–base shifts, and illness can mask potassium deficiency at the blood level.

Why this matters in a high-ATP environment

Extracellular ATP activates purinergic receptors that increase neuronal excitability. Potassium gradients are critical for maintaining neuronal resting membrane potential and electrical calm (Cekic and Linden, 2016).

In chronic inflammatory states, impaired intracellular potassium handling may increase vulnerability to:

  • Nervous system irritability
  • Autonomic instability
  • Sensory overstimulation

Potassium does not block purinergic signalling directly, but adequate intracellular potassium supports neuronal polarity and stability in a noisy danger-signal environment.

Safety note: Potassium support must be approached cautiously in individuals with kidney disease, those taking potassium-sparing diuretics, ACE inhibitors, or ARBs, or those with heart rhythm disorders – and should only be adjusted under medical supervision.

Vitamin D supplementation: timing matters

When VDR sensitivity is reduced, added vitamin D may remain unutilized in circulation.

Excess circulating vitamin D has been shown to reduce folate transport, particularly into the central nervous system. Folate is essential for:

  • Neurotransmitter balance
  • Antioxidant support
  • Autonomic nervous system regulation (Bailey and Gregory,1999)

This can worsen neurological and autonomic symptoms. Vitamin D itself is not harmful – the issue is supplementation before receptor sensitivity is restored (Eyles et al., 2013).

Environmental stressors may further complicate vitamin D physiology. Experimental models have shown that chronic exposure to electromagnetic fields can disrupt vitamin D status and bone-related endocrine signalling, suggesting that receptor-level or regulatory interference may occur independently of intake (Gungor et al., 2015).

Where MetaDichol and Olmesartan fit

Restoring VDR responsiveness may be more important than increasing vitamin D intake.

MetaDichol

MetaDichol is derived from long-chain fatty alcohols and used at very low doses. It appears to:

  • Modulate nuclear receptors
  • Reduce receptor ‘noise’
  • Support re-sensitization of the VDR without overstimulation

Olmesartan

Olmesartan – an angiotensin II receptor blocker – reduces inflammatory and vascular stress. It has also been described as a partial agonist of the VDR, potentially:

  • Stabilizing receptor signalling
  • Reducing inflammatory or biotoxin interference with receptor function

These approaches may be complementary, supporting receptor responsiveness through different mechanisms (Marshall and Heil, 2017).

Important caution: Olmesartan lowers blood pressure and may worsen symptoms in individuals with hypotension or POTS-like conditions unless carefully supervised.

Why immune modulation must come before metabolic enhancement

Attempting to boost mitochondrial or hormonal activity while immune danger signals remain active often worsens symptoms.

Immune stabilization and resolution should occur before:

  • Aggressive metabolic stimulation
  • Hormonal enhancement
  • High-dose vitamin D

Only when danger signalling quiets can metabolism recover safely.

Why treatment keeps repeating

Repeated antimicrobial or gut-focused protocols often fail, not because they are ineffective, but because immune resolution has not been restored.

This leads to a cycle of temporary improvement followed by relapse, reflecting misdirected effort rather than therapeutic failure.

The bigger picture

Chronic illness emerges when:

  • Macrophage clean-up fails
  • Neutrophils remain overactive
  • Copper is misallocated
  • Mitochondria destabilize
  • ATP escapes as a danger signal
  • Neuronal stability is compromised
  • Vitamin D receptor sensitivity declines
  • Folate, antioxidant systems, and electrolyte balance are disrupted

Each process reinforces the others.

Healing, in this model, is not about eliminating a single pathogen, but about restoring immune coherence so that the body can resolve threats on its own.

References

Bahnan, W., Wrighton, S., Sundwall, M., Bläckberg, A., Larsson, O., Höglund, U., Khakzad, H., Godzwon, M., Walle, M., Elder, E. and Strand, A.S. (2022) Spike-dependent opsonization indicates both dose-dependent inhibition of phagocytosis and that non-neutralizing antibodies can confer protection to SARS-CoV-2. Frontiers in immunology, 12, p.808932. Available at: https://doi.org/10.3389/fimmu.2021.808932

Bailey, L.B. and Gregory III, J.F. (1999) Folate metabolism and requirements. The Journal of nutrition, 129(4), pp.779-782. Available at: https://doi.org/10.1093/jn/129.4.779

Brown, G.C. and Borutaite, V. (1999, September) Nitric oxide, cytochrome c and mitochondria. In Biochemical Society Symposia (Vol. 66, pp. 17-25). Portland Press Limited. Available at: https://doi.org/10.1042/bss0660017

Cekic, C. and Linden, J. (2016) Purinergic regulation of the immune system. Nature Reviews Immunology, 16(3), pp.177-192. Available at: https://doi.org/10.1038/nri.2016.4 and https://www.researchgate.net/ publication/296477247

Eyles, D.W., Burne, T.H. and McGrath, J.J. (2013) Vitamin D, effects on brain development, adult brain function and the links between low levels of vitamin D and neuropsychiatric disease. Frontiers in neuroendocrinology, 34(1), pp.47-64. Available at: https://doi.org/10.1016/j.yfrne.2012.07.001

Gungor, H.R., Akkaya, S., Ok, N., Yorukoglu, A., Yorukoglu, C., Kiter, E., Oguz, E.O., Keskin, N. and Mete, G.A. (2015) Chronic exposure to static magnetic fields from magnetic resonance imaging devices deserves screening for osteoporosis and vitamin D levels: a rat model. International Journal of Environmental Research and Public Health, 12(8), pp.8919-8932. Available at: https://doi.org/10.3390/ijerph120808919

Hoepel, W., Chen, H.J., Geyer, C.E., Allahverdiyeva, S., Manz, X.D., de Taeye, S.W., Aman, J., Mes, L., Steenhuis, M., Griffith, G.R. and Bonta, P.I. (2021) High titers and low fucosylation of early human anti–SARS-CoV-2 IgG promote inflammation by alveolar macrophages. Science translational medicine, 13(596), p.eabf8654. Available at: DOI: 10.1126/scitranslmed. abf8654

Marshall, T.G. and Heil, T.J.R. (2017) Electrosmog and autoimmune disease. Immunologic Research, 65(1), pp.129-135. Available at: https://doi.org/10.1007/s12026-016-8825-7

Percival, S.S. (1998) Copper and immunity. The American Journal of Clinical Nutrition, 67(5), pp.1064S-1068S. Available at: https://doi.org/10.1093/ajcn/67.5.1064S

Pickart, L., 2008. The human tri-peptide GHK and tissue remodeling. Journal of Biomaterials Science, Polymer Edition, 19(8), pp.969-988. Available at: https://doi.org/10.1163/156856208784909435

Salina, A.C., Dos-Santos, D., Rodrigues, T.S., Fortes-Rocha, M., Freitas-Filho, E.G., Alzamora-Terrel, D.L., Castro, I.M., da Silva, T.F.F., de Lima, M.H., Nascimento, D.C. and Silva, C.M. (2022) Efferocytosis of SARS-CoV-2-infected dying cells impairs macrophage anti-inflammatory functions and clearance of apoptotic cells. Elife, 11, p.e74443. Available at: https://doi.org/10.7554/eLife.74443

Uriu-Adams, J.Y. and Keen, C.L. (2005) Copper, oxidative stress, and human health. Molecular Aspects of Medicine, 26(4-5), pp.268-298. Available at: https://doi.org/10.1016/j.mam.2005.07.015

/0 Comments/by

Post lockdown disease paradigm: Solutions for an age of perpetual inflammation

By Justin Gregory Maguire

BSc (Hons) Nutritional Science.

PG Dip Functional Blood Chemistry Analysis.

BTech Kinesiology and Applied Anatomy.

In the modern world many people are beginning to feel as though their bodies are living in a form of quiet internal emergency, which could stem from an unresolved tension that lingers long after visible stressors have faded. This sense of being simultaneously inflamed, fatigued, wired, hypersensitive, and neurologically burdened may reflect how our immune and metabolic systems interpret the signals of a technological era that human biology never evolved to navigate.

Today’s environment is saturated with non-native electromagnetic fields (nnEMF) emitted from mobile infrastructure, Wi-Fi, and wireless devices. Experimental evidence shows that these fields can increase reactive oxygen species, promote oxidative stress, and disturb antioxidant defences within the neural and immune tissues, potentially influencing mitochondrial stability and inflammatory tone (Schuermann and Mevissen, 2021). This oxidative tension may subtly prime the innate immune system towards a ‘ready-to-fire’ state.

At the same time, growing research into post-viral syndromes reveals that fragments of viral proteins – particularly the SARS-CoV-2 S1 subunit – can persist in immune cells such as non-classical monocytes for many months after infection. These fragments are not active viruses, but their presence may sustain innate immune activation and inflammatory signalling long after the initial illness has resolved (Patterson et al., 2022). Such persistence mirrors what is observed in other post-infectious conditions and may explain why some individuals experience prolonged fatigue, pain, sensory sensitivity, dysautonomia, or cognitive dysfunction despite clear recovery from the acute infection. The PNAS (Proceedings of the National Academy of Sciences of the United States of America) review on long Covid similarly notes that lingering viral antigens can provoke ongoing immune responses, endothelial inflammation, and microvascular dysfunction – patterns consistent with a long-standing inflammatory echo rather than a new contagious threat (Shaffer, 2022).

This ongoing activation may push the body into the Cell Danger Response (CDR), a protective metabolic state characterised by reduced ATP production, increased extracellular ATP signalling, antiviral activation, and widespread mitochondrial reprogramming. According to Naviaux, a single burst of extracellular ATP can drop whole-body oxygen consumption by approximately 74% and shift hundreds of metabolites within minutes (Naviaux, 2014). These rapid changes reflect the body’s attempt to halt pathogen spread and prioritise defence, but when prolonged, they create a state of biochemical stagnation where healing no longer progresses. NK (Natural Killer) cells – innate immune cells with increased adaptable vigilance against cancer and covert pathogens, such as cell wall deficient bacteria or DNA viruses like Epstein Barr – may begin to exhaust, neutrophils may behave hypervigilantly, and cytokine traffic may remain disordered. Astroglia within the central nervous system may enter a persistent state of activation, influencing spinal ganglia signalling and amplifying pain and sensory processing, potentially contributing to fibromyalgia-like symptoms and neuropathic sensations (Naviaux et al., 2017).

These processes align with a contemporary view of mitochondria that extends far beyond energy production. Research from Picard and colleagues describes mitochondria as information processors – organelles that continuously integrate hormonal, immune, metabolic, and environmental cues to determine how cells respond to their surroundings (Picard, 2023).

Through this lens, chronic symptoms do not appear as isolated organ malfunction but as a miscalibration communication network across the immunity, metabolism, and neural regulation network.

The first step towards restoring balance often involves calming innate immunity. Pattern-recognition receptors such as TLR4 and TLR9 may remain in a hyper-responsive state, driving caspase activation, extracellular ATP release, and P2X7/P2Y-mediated ion flux. Patterson’s long Covid data show that individuals with persistent symptoms often display characteristic cytokine patterns involving IL-6, TNF-α, IFN-γ, sCD40L, VEGF, and CCL5/RANTES – molecules associated with vascular inflammation, endothelial dysfunction, dysautonomia, and sensory hypersensitivity (Patterson et al., 2022). These inflammatory signals are not random: they form a consistent pattern across many chronic inflammatory states, including ME/CFS, long Lyme, and post-viral fatigue, suggesting that the immune system may have become stuck in a defensive configuration.

Supporting immune recalibration may involve natural immunomodulators such as saponins, cepharanthine, kalawalla, thymic peptides, and low-dose naltrexone, or pharmaceutical agents such as maraviroc, olmesartan, and statins. Statins, for instance, can down-regulate fractalkine, reducing the adhesion of inflammatory monocytes to vascular endothelium, while maraviroc modulates CCR5 to limit inflammatory cell migration and repolarise monocytes towards a less inflammatory phenotype(Patterson et al., 2022). These interventions do not suppress immunity; rather, they help correct misguided danger signalling so that the system can return to a healthier baseline.

Once innate immune tone softens, neurotransmitter networks often require restoration. Inflammation diverts tryptophan away from serotonin and tryptamine synthesis into the kynurenine pathway, reducing serotonergic stability and increasing the likelihood of dopamine oxidative stress. Patterson’s analysis reveals that cytokines such as IL-1β, IL-6, and TNF-α correlate strongly with decreased serotonin and increased fatigue, dysautonomia, and cognitive disruption (Patterson et al., 2022). When dopamine oxidises into quinones under inflammatory pressure, the burden on mitochondrial redox pathways intensifies, affecting NAD/NADPH availability.Supporting thyroid function and cortisol availability is typically essential before serotonergic interventions – whether SSRIs/SNRIs or, under clinical supervision, psychedelic-assisted therapy – can help recalibrate limbic circuitry.

A similar pattern unfolds with the glutamate–GABA system. NAD depletion via CD38 impairs EAAT2 glutamate clearance, promotes pseudo-hypoxic redox signalling, and increases excitotoxic susceptibility. Mitochondrial stress experiments in ME/CFS models show that serum from affected individuals can induce mitochondrial fragmentation and antiviral-like metabolic states in naïve cells, illustrating how immune signals can reshape neural energy dynamics (Schreiner et al., 2020). In this context, interventions that reduce glutamate load or strengthen inhibitory signalling – such as niacin, pinealon, theanine, Selank, or muscimol – may help restore neural balance.

The endocrine system forms the final pillar in this integrative picture. Hypothyroidism can disrupt D2 receptor regulation, increase prolactin tendencies, reduce glucocorticoid-receptor sensitivity, and heighten neuroinflammatory reactivity. Because mitochondrial phenotypes differ across tissues, thyroid imbalances manifest differently depending on whether the dysfunction is hepatic or peripheral (Picard, 2023).

Within this context, endocrine adaptations emerge differently across tissues and axes:

  • Resmetirom may support hepatocellular mitochondrial function, while peripheral mitochondrial insufficiency may respond to thyreogen peptides, iodine or selenium repletion, or context-sensitive thyroid support such as T2 when inflammatory granulation remains high.
  • Disruption of stress-regulatory and endocrine signalling has been increasingly observed in long Covid, with implications for inflammation, autonomic balance, and cognitive function (Shaffer, 2022).

Across these systems, a clear narrative emerges: the immune system, mitochondria, neural circuits, and endocrine rhythms are not malfunctioning independently; they are reacting to a perceived state of danger that has not yet resolved. The task of recovery is not to punish or force these systems back into compliance but to help them remember what safety feels like.

Healing, in this context, becomes less about fixing broken parts and more about helping the body unlearn a state of emergency. It involves guiding the immune system, mitochondria, endocrine rhythms, and neural circuits to recognise that the threat has passed and that it is safe to soften again. As these systems gradually release their defensive posture, their communication becomes more fluid, their energy more coherent, and the whole organism begins to return to a natural rhythm of regulation. In that renewed synchrony – where metabolism, immunity, and neural signalling breathe together once more – the body rediscovers its innate capacity to heal.

References

Naviaux, R.K. (2014) Metabolic features of the cell danger response. Mitochondrion, 16, pp.7-17. Available at: https://doi.org/10.1016/j.mito.2013.08.006

Naviaux, R.K., Curtis, B., Li, K., Naviaux, J.C., Bright, A.T., Reiner, G.E., Westerfield, M., Goh, S., Alaynick, W.A., Wang, L. and Capparelli, E.V. (2017) Low‐dose suramin in autism spectrum disorder: a small, phase I/II, randomized clinical trial. Annals of Clinical and Translational Neurology, 4(7), pp.491-505. Available at: https://doi.org/10.1002/acn3.424

Patterson, B.K., Francisco, E.B., Yogendra, R., Long, E., Pise, A., Rodrigues, H., Hall, E., Herrera, M., Parikh, P., Guevara-Coto, J. and Triche, T.J. (2022) Persistence of SARS CoV-2 S1 protein in CD16+ monocytes in post-acute sequelae of COVID-19 (PASC) up to 15 months post-infection. Frontiers in Immunology, 12, p.746021. Available at: https://doi.org/10.3389/fimmu.2021.746021

Picard, M. (2023) Martin Picard: Exploring the Mind-Mitochondria Connection. Columbia University Irving Medical Center. Available at: https://www.cuimc.columbia.edu/news/martin-picard-exploring-mind-mitochondria-connection

Schreiner, P., Harrer, T., Scheibenbogen, C., Lamer, S., Schlosser, A.,  Naviaux, R.K. and Prusty, B.K. (2020) Human Herpesvirus-6 Reactivation, Mitochondrial Fragmentation, and the Coordination of Antiviral and Metabolic Phenotypes in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. ImmunoHorizons 4(4) p.201–215. Available at: https://doi.org/10.4049/immunohorizons.2000006

Schuermann, D. and Mevissen, M. (2021) Manmade electromagnetic fields and oxidative stress—biological effects and consequences for health. International Journal of Molecular Sciences, 22(7), p.3772. Available at: Manmade Electromagnetic Fields and Oxidative Stress.pdf and https://doi.org/10.3390/ijms22073772 Shaffer, L. (2022) Lots of long COVID treatment leads, but few are proven. Proceedings of the National Academy of Sciences (PNAS), 119(36), e2213524119. Available at: https://doi.org/10.1073/pnas.2213524119

/0 Comments/by

DHEA: A Smart Modulator for Immune Overreaction and Hormonal Balance

Introduction

You may know DHEA (dehydroepiandrosterone) as an adrenal hormone that declines with age, but it’s more than a precursor to sex hormones – it plays a key role in how your immune system balances itself. In conditions where immune cells overreact – such as Mast Cell Activation Syndrome (MCAS) or other TLR4-driven inflammatory states – DHEA may serve as a modulatory brake, helping calm the storm. But DHEA also has complex metabolic pathways, and under certain circumstances, it may convert into estrogen at a higher rate, particularly in the setting of inflammation and metabolic dysfunction.

Modulating Immune Receptors: TLR4 and the Inflammatory Alarm

The immune system senses danger using “radar” receptors called toll-like receptors (TLRs). TLR4 specifically reacts to lipopolysaccharide (LPS) from bacteria and can trigger powerful inflammation.

Research indicates that:

  • DHEA helps reduce TLR4-driven inflammation, limiting release of pro-inflammatory signals.
  • By toning down this TLR4 response, DHEA can be a protective factor when immune overreaction is a significant problem.

Calming Mast Cells in MCAS and Allergic Inflammation

Mast cells – key players in allergies and MCAS – release chemicals like histamine in response to triggers. In studies, DHEA has been shown to reduce mast cell degranulation, which helps dampen allergic and inflammatory symptoms such as gut irritation, flushing, or hives.

Balancing Cortisol with 11β-HSD Pathways

Cortisol, the stress hormone, and DHEA share the same adrenal origins. The enzyme 11β-hydroxysteroid dehydrogenase (11β-HSD) helps regulate cortisol activity inside cells.

  • DHEA supports a balanced cortisol-to-DHEA ratio, which is important for avoiding immune overactivation.
  • This balance allows the immune system to stay adaptable without collapsing into exhaustion or flaring into overdrive.

The Role of Mitochondria in Cortisol and Immune Balance

Mitochondria, the energy powerhouses, are also central to cortisol production. Cholesterol conversion into pregnenolone, the first step in cortisol synthesis, takes place in adrenal mitochondria. When mitochondria falter, cortisol production falls, and the balance with DHEA is disrupted.

Thus, mitochondrial health doesn’t just impact energy levels – it shapes how DHEA and cortisol interact to regulate inflammation.

DHEA, Estrogen Conversion, and Cytokine Storms

An important consideration is that DHEA can convert into estrogen through enzymatic pathways, especially when the enzyme aromatase is upregulated. This probability increases in states of:

  • Cytokine storms and inflammation: Pro-inflammatory cytokines (IL-6, TNF-α, prostaglandins) boost aromatase activity, increasing the likelihood that DHEA is diverted toward estrogen production.
  • Adiposity and visceral fat accumulation: Fat tissue is rich in aromatase, meaning obesity and insulin resistance can drive more estrogen from DHEA.
  • Hepatic dysfunction: Conditions such as fatty liver or fibrosis impair estrogen clearance, causing build-up.

This means that in autoimmune-like states with inflammatory surges, supplementing DHEA without addressing these underlying drivers could unintentionally lead to excess estrogen, which may complicate hormone balance further.

Practical Tools to Address Conversion Risk

  • Semaglutide and visceral fat: By reducing visceral adiposity, semaglutide (a GLP-1 agonist) indirectly reduces aromatase expression in fat tissue, lowering estrogen conversion pressure.
  • Resmetirom and hepatic fibrosis: This novel thyroid hormone receptor-β agonist has shown promise in improving fatty liver disease and reducing fibrosis. By restoring healthier liver function, resmetirom may improve estrogen clearance and reduce the conditions that favour DHEA’s conversion to estrogen.
  • Proteolytic enzymes and hepatic support: Enzymes such as serrapeptase and nattokinase have been studied for their anti-fibrotic and anti-inflammatory potential. Supporting liver health helps maintain estrogen clearance.
  • Curcumin and cytokine moderation: Curcumin, from turmeric, is known to reduce NF-κB activity and inflammatory cytokine production. By blunting cytokine storms, it reduces aromatase upregulation and thus estrogen buildup.

⚠️ Important Note: Both semaglutide and resmetirom are powerful interventions with effects that extend across multiple physiological systems. They are not simple over-the-counter tools but prescription medications that must be guided by a clinician. Before considering them, it is essential to consult a qualified medical provider to evaluate risks, benefits, and whether they are appropriate for your health profile.

Special Consideration: Long-Haul COVID and Exercise Recovery

An additional area of interest is long-haul COVID, where patients often struggle with exercise intolerance and poor recovery. One factor may be an ongoing macrophage activation syndrome-like state, leading to persistent inflammation and fatigue.

Given its ability to dampen TLR4-driven cytokine surges, modulate mast cell activity, and support a balanced cortisol-DHEA ratio, DHEA could hold potential as part of a broader management strategy for this group. Yet here, too, the risk of DHEA converting into estrogen in an inflamed, adipose, or fibrotic environment underscores the importance of identifying and addressing the causative drivers of inflammation first.

Practical Points to Consider

  • Test first: Assess DHEA, cortisol, estrogen levels, and metabolic markers before supplementing.
  • Address inflammation: Reduce cytokine drivers (diet, curcumin, lifestyle).
  • Target adiposity and insulin resistance: Approaches like semaglutide or lifestyle-driven weight loss reduce aromatase burden.
  • Support the liver: Resmetirom in fibrosis, proteolytic enzymes, and nutrient-rich strategies can improve clearance of estrogens.
  • Use DHEA carefully: Too much may raise estrogen; too little may be ineffective. Age, sex, and context all matter.

Final Thoughts

DHEA is not a blunt tool – it is an immune and hormonal tuner. It calms overactive TLR4 pathways, steadies mast cells, and works in balance with cortisol. But in inflamed or metabolically stressed states, it can convert more readily into estrogen, especially when cytokine storms, visceral fat, or liver dysfunction are present.

That’s why effective use of DHEA requires a whole-system view: balance inflammation, reduce adiposity, support the liver, and profile cortisol before supplementation. With these safeguards in place and with careful consultation if medications like semaglutide or resmetirom are considered – DHEA can help restore harmony, quieting the storm without tipping the body into a new imbalance.

Medical Advice Disclaimer: This content is for educational purposes only and is not a substitute for professional medical advice. Always consult your healthcare provider for personalized medical care.

/0 Comments/by

Copper, Fasting, and the Hidden Link Between Energy and Immunity

Copper, Fasting, and the Hidden Link Between Energy and Immunity

When people think of fasting, they often imagine it as a universal path to better health: weight loss, cellular repair, and sharper thinking. Indeed, fasting has many well-documented benefits, from stimulating cellular clean-up processes (autophagy) to enhancing the activity of longevity-linked proteins called sirtuins. But like any biological process, fasting is not one-size-fits-all. The state of the body’s nutrient stores – especially copper – can radically change whether fasting helps or harms.

Copper may not be as well-known as iron or zinc, but it is just as essential. It plays a central role in how our cells make energy and how our immune system recognises threats. In situations of poor copper availability, fasting can sometimes backfire, putting extra stress on the brain and immune system. To understand why, let’s take a closer look at the science in a way that connects energy metabolism, red blood cells, immune balance, and the different forms in which copper exists in the body.

Copper’s Two Faces: Cu¹⁺ and Cu²⁺

Copper exists in two main biological forms:

  • Cu¹⁺ (cuprous copper, 28 electrons)
  • Cu²⁺ (cupric copper, 27 electrons)

This small difference in electron count has major biological consequences. Cu¹⁺ is the reduced form, most effective for driving the proton pump of cytochrome c oxidase (Complex IV) in mitochondria – the final enzyme of the energy chain. By enabling protons to be pushed across the mitochondrial membrane, Cu¹⁺ powers ATP synthase, the turbine that generates cellular energy.

Cu²⁺, in contrast, is more oxidising. It circulates mostly extracellularly, often bound to proteins like ceruloplasmin. When unbuffered, excess Cu²⁺ can drive free radical chemistry, contributing to oxidative stress. The balance between these two states – Cu¹⁺ inside cells and Cu²⁺ in circulation – is tightly controlled by the body.

When too little Cu¹⁺ is available for mitochondria, electrons back up in the energy chain, leak out, and form damaging superoxide radicals. Over time this leads to mitochondrial instability, cytochrome c loss, and accelerated cellular aging.

Fasting and Mitochondrial Stress

Fasting is often praised for boosting health. It encourages cells to burn fat, activate protective proteins (sirtuins), and clean out damaged components (autophagy). But fasting also increases the flow of electrons through the mitochondrial chain.

If Complex IV is well-supplied with Cu¹⁺, this added traffic is handled efficiently. If copper delivery is poor, however, the extra electron load produces more leaks and free radicals. In such cases, fasting could paradoxically worsen oxidative stress, especially in the brain. This is why fasting may be contraindicated in states of copper deficiency or poor intracellular copper delivery.

Copper in the Blood: Red Cells, Ratios, and Immune Clues

Copper balance isn’t just about “how much” is in the body – it’s about where it is, and in what form. Red blood cells (RBCs) carry significant amounts of copper to tissues, supporting oxygen use and mitochondrial function.

Researchers also look at mineral ratios and immune cell counts for clues:

  • Copper-to-zinc ratio: Too much zinc can suppress copper; balance between the two is often more important than the absolute value.
  • Neutrophil-to-lymphocyte ratio (NLR): Copper influences this in two very different ways:
  • Overall copper deficiency can impair neutrophil development, leading to neutropenia (low neutrophil count) and a weakened immune defence.
  • Excess extracellular Cu²⁺ with poor intracellular Cu¹⁺ availability can drive neutrophil over-activation, resulting in a heightened NLR. This can tip the body toward autoimmune-type inflammation, where neutrophils release sticky webs called neutrophil extracellular traps (NETs). While NETs help fight infection, in excess they contribute to fibrotic tissue build-up and organ damage.

In summary: too little copper weakens defence, while the wrong distribution of copper can overstimulate immunity and drive tissue damage.

Different Copper Interventions

Copper can be replenished in different forms, and the form makes a difference:

  • Chelated or bisglycinate copper: Common supplement forms, supportive for general intake, but not always optimal for intracellular delivery.
  • Cuprous nicotinic acid (Cu¹⁺-NA): A form that delivers copper in the active 28-electron (Cu¹⁺) state that mitochondria prefer, potentially improving direct uptake into cells and Complex IV function.
  • GHK-Cu: A naturally occurring tripeptide (glycyl-L-histidyl-L-lysine bound to copper). Its key functions are:
  • Binding excess extracellular Cu²⁺ to reduce oxidative stress.
  • Transporting copper into cells where it can be converted to Cu¹⁺ and support mitochondrial energy production.
  • Supporting antioxidant systems, including glutathione recycling, to defend against oxidative damage.
  • Promoting tissue repair and reducing inflammation, which has been shown in wound-healing and anti-fibrotic research.

In the context of fasting and copper imbalance, GHK-Cu may help by both cleaning up harmful extracellular copper and enhancing intracellular copper availability, protecting energy metabolism and immune balance.

Immunity and Energy: Two Sides of Copper’s Role

Copper deficiency doesn’t just starve mitochondria of energy – it also blunts the immune system’s ability to recognise and respond to threats. Enzymes that help immune cells “present” antigens (the molecular ID tags of invaders) are copper-dependent. Without copper, immune precision falters: the body may underreact with weak infection control or overreact with inappropriate inflammation.

When extracellular Cu²⁺ dominates but intracellular Cu¹⁺ is lacking, the risk shifts: neutrophils become hyperactive, NLR rises, and excessive NET formation can trigger autoimmune inflammatory responses and fibrosis.

Thus, copper sits at a crossroads: it powers the energy factories of our neurons and immune cells, and it fine-tunes the recognition systems that govern immunity.

Benefits of Fasting – When Copper Is in Balance

With balanced copper, fasting can:

  • Enhance autophagy: Clearing damaged parts of cells.
  • Activate sirtuins: Proteins linked to DNA repair, mitochondrial efficiency, and stress resilience.
  • Reset metabolism: Improve insulin sensitivity and hormone balance.

But without copper – especially Cu¹⁺ – these benefits may not appear, and fasting could add to stress.

The Flaws and Considerations

  1. Not universal: Fasting can worsen stress in copper-deficient states.
  2. Form matters: Cu¹⁺ forms (like cuprous nicotinic acid) may be more directly beneficial for mitochondria than generic salts.
  3. Immune risk: Too little copper weakens immunity, while poor copper distribution can overstimulate neutrophils and promote autoimmune-like inflammation.

Moving Toward Balance

The lesson is not to abandon fasting altogether, but to approach it wisely. Before engaging in prolonged fasting:

Assess mineral status, especially copper and zinc.

  • Ensure copper is available in the right form for mitochondria.
  • Consider support from GHK-Cu if extracellular copper overload is suspected.
  • Maintain glutathione and antioxidant systems to buffer stress.

Final Thought

Fasting is a powerful tool – but like all tools, its effects depend on the foundation beneath it. Copper, in both its forms, is central to that foundation. With balanced Cu¹⁺ and Cu²⁺, fasting enhances energy, brain health, and immunity. Without that balance, fasting risks accelerating decline through oxidative stress, immune imbalance, and fibrosis.

Medical Advice Disclaimer: This content is for educational purposes only and is not a substitute for professional medical advice. Always consult your healthcare provider for personalized medical care.

/0 Comments/by

Is Your Jaw Pain More Than Just Stress? Exploring the Hidden Link Between Viral Reactivation and TMJ Dysfunction

Temporomandibular Joint Dysfunction – or TMJ, is a common yet often misunderstood condition. It typically shows up as jaw pain, popping sounds, facial tension, or difficulty chewing. Many people assume it’s caused purely by stress, teeth grinding, or poor posture. While these factors certainly play a role, emerging science points to a deeper, lesser-known culprit hiding in plain sight: stealth viral infections – particularly the Epstein-Barr Virus (EBV).

You may have heard of EBV as the virus behind mononucleosis, often called “the kissing disease.” What’s not as widely known is that EBV, once inside your body, never truly goes away. It hides silently in your cells, especially immune cells, waiting for an opportunity to reactivate. This reactivation doesn’t always bring on full-blown illness. Instead, it can cause vague, persistent symptoms – fatigue, brain fog, muscle aches, and, surprisingly, jaw and facial pain.

So how does a virus like EBV connect to jaw tension?

Let’s start with the immune system. When stealth viruses reactivate (often due to chronic stress, poor sleep, or a weakened immune system), they can cause low-grade inflammation throughout the body. Inflammation is your body’s natural defense mechanism, but when it becomes chronic, it starts to attack healthy tissues – including joints.

The temporomandibular joint is a small but complex hinge that connects your jawbone to your skull. Like any joint, it can become inflamed. If your body is already dealing with systemic inflammation due to a reactivated virus, the TMJ can become one of the unintended targets. That inflammation may not only cause pain but also increase nerve sensitivity, leading to jaw tightness, facial aches, and even referred pain to the ears or temples.

But there’s more. EBV can also affect the nervous system. One of the main nerves involved in jaw movement and facial sensation is the trigeminal nerve. When stealth viruses disturb this nerve – either through inflammation or direct irritation – it can mimic or worsen TMJ symptoms, sometimes leading doctors and patients down a path of dental treatments that miss the root cause.

Furthermore, the stress of chronic viral activation can create a vicious cycle. When you’re not feeling well, you’re more likely to clench your jaw, grind your teeth at night, or develop poor posture – all of which strain the TMJ further.

So, what can you do?

First, don’t panic – this doesn’t mean every case of TMJ is viral. But if you’ve struggled with chronic TMJ symptoms, fatigue, or brain fog, and traditional treatments haven’t helped, it might be worth considering an underlying immune or viral issue. Supportive therapies that reduce inflammation, strengthen the immune system, and regulate stress can sometimes provide unexpected relief—not just for your energy levels, but for your jaw too.

In short, your body speaks in whispers before it screams. That nagging jaw pain could be more than muscular tension – it might be your immune system asking for help.

Medical Advice Disclaimer: This content is for educational purposes only and is not a substitute for professional medical advice. Always consult your healthcare provider for personalized medical care.

/0 Comments/by

Nature, NK Cells, and Stealth Viral Protection: Restoring Adrenal Health

Nature, NK Cells, and Stealth Viral Protection: Restoring Adrenal Health

Building on our previous discussion about stealth viral infections and their subtle yet profound impacts on adrenal function, this week’s edition draws inspiration from a recent TIME feature titled “The Healing Power of Nature”. This insightful article highlights how nature exposure significantly enhances natural killer (NK) cell activity, crucial for managing stealth viruses such as Epstein-Barr virus (EBV), Cytomegalovirus (CMV), and HHV-6.

Stealth viruses quietly disrupt adrenal health through chronic, low-grade inflammation. NK cells represent a frontline defence, rapidly identifying and eliminating virally-infected cells before these pathogens can embed deeply within tissues, including the adrenal cortex. Notably, research has demonstrated that even short-term exposure to natural environments, such as forests, boosts NK cell numbers and their cytotoxic capacity for extended periods, offering sustained protection against viral infiltration (1).

The enhancement of NK cells by nature exposure helps counteract the persistent immune evasion strategies employed by stealth viruses. By elevating NK cell activity while simultaneously reducing cortisol production – a hallmark of stress and inflammation – nature exposure disrupts the harmful cycle linking viral infections to adrenal fatigue and mitochondrial dysfunction. This dual action creates a beneficial hormonal and immunological environment, significantly mitigating the chronic stress exploited by these viruses (2).

Complementing nature exposure with specific nutraceutical strategies can further bolster NK cell function and provide crucial adrenal support. Active Hexose Correlated Compound (AHCC) has been clinically shown to significantly increase NK cell activity. Astragalus root enhances both NK cell function and adrenal resilience. Essential nutrients like Vitamin D3 and Zinc are foundational for optimal immune responses and NK cell efficiency. Additionally, adaptogenic herbs such as Ashwagandha and Rhodiola effectively normalize cortisol levels, thus reducing adrenal stress and supporting mitochondrial health. Furthermore, nutraceuticals like IP6 (inositol hexaphosphate) and transfer factors have demonstrated notable improvements in NK cell activity, providing additional immune-enhancing support.

In cases where stealth viral infections inhibit vitamin D receptor (VDR) function, the use of certain antihypertensive medications such as angiotensin receptor blockers (ARBs) might be beneficial. These medications have been shown to modulate immune responses by acting on VDR pathways, thereby potentially restoring vitamin D signalling impaired by viral infections (3).

Alongside nutraceutical interventions, lifestyle practices are fundamental in reinforcing immune and adrenal resilience. Regular visits to natural settings like forests or parks amplify NK cell activity and reduce adrenal stress. Mindfulness practices effectively lower cortisol-driven inflammation, limiting opportunities for viral reactivation. Moderate exercise consistently boosts NK cells and enhances mitochondrial and adrenal health. Furthermore, optimizing sleep quality supports adrenal recovery, boosts NK cell production, and facilitates mitochondrial repair.

At a cellular level, chronic stealth viral infections trigger sustained inflammation, perpetuating what has been termed the cellular “danger response.” This pathological metabolic state severely impairs mitochondrial efficiency and adrenal function. However, regular nature exposure therapeutically interrupts this process by simultaneously reducing cortisol, enhancing NK cell surveillance, and improving mitochondrial energy production, effectively addressing the underlying pathophysiological mechanisms (2).

To practically integrate these insights, a comprehensive protocol addressing stealth viral impacts should include routine nature exposure – such as weekly forest bathing or visits to parks – to boost NK cells and adrenal health. Nutraceuticals like AHCC, Astragalus, Vitamin D3, Zinc, adaptogenic herbs, IP6, and transfer factors are vital supplements. Lifestyle practices including mindfulness meditation, regular moderate exercise, optimized sleep patterns, and controlled cold exposure further support resilience. Lastly, nutritional support with B vitamins and magnesium is recommended to strengthen mitochondrial and adrenal vitality.

In conclusion, integrating nature exposure, targeted nutraceuticals, supportive lifestyle interventions, and potentially antihypertensive medications offers a robust and unified approach to managing stealth viral infections and restoring adrenal health. By enhancing NK cell activity, reducing cortisol-driven inflammation, and supporting mitochondrial function, we effectively protect adrenal integrity and transform chronic stress into sustained health and vitality.

Until our next edition,

Justin.

References:

Li Q, Morimoto K, Nakadai A, Inagaki H, Katsumata M, Shimizu T, et al. A day trip to a forest park increases human natural killer activity and the expression of anti-cancer proteins in male subjects. J Biol Regul Homeost Agents. 2010;24(2):157-65.

Irwin MR, Cole SW. Reciprocal regulation of the neural and innate immune systems. Nat Rev Immunol. 2011;11(9):625-32. doi: 10.1038/nri3042.

Marshall TG, Lee RE, Marshall FE. Common angiotensin receptor blockers may directly modulate the immune system via VDR, PPAR and CCR2b. Theor Biol Med Model. 2006 Jan 10;3:1. doi: 10.1186/1742-4682-3-1.

Medical Advice Disclaimer: This content is for educational purposes only and is not a substitute for professional medical advice. Always consult your healthcare provider for personalized medical care.

/0 Comments/by

Stealth Viral Infections, Autoimmunity, and the Hidden Impact on Adrenal Health

Stealth Viral Infections, Autoimmunity, and the Hidden Impact on Adrenal Health

In the world of modern medicine, symptoms like chronic fatigue, low blood pressure, brain fog, and digestive issues are often approached in isolation. However, a growing body of research – and a deeper understanding promoted by leaders like Professor Robert Naviaux, Dr. Dietrich Klinghardt, and Dr. Paul Cheney – suggests that underlying stealth viral infections may be quietly driving these diverse expressions of disease. Among the most affected systems? The adrenal glands, immune signalling, and gut integrity.

The Role of Stealth Viruses in Autoimmune-Like Presentations

Stealth viruses are not your typical infections. These include chronic, low-grade or latent viruses such as cytomegalovirus (CMV), Epstein-Barr virus (EBV), and human herpesvirus-6 (HHV-6). They often escape routine detection and don’t always cause acute symptoms. Instead, they subtly disrupt cellular function and trigger abnormal immune responses that resemble autoimmune conditions.

One of the most significant connections being explored is between CMV and the adrenal glands. In healthy individuals, the adrenal glands produce critical hormones like cortisol and aldosterone, which regulate everything from blood pressure to inflammation. But CMV has been shown to infect adrenal tissue directly in some individuals, especially those who are immunocompromised.

CMV and 21-Hydroxylase Antibody Mimicry (Theoretical Risk)

What makes CMV particularly insidious is its potential to theoretically mimic adrenal autoimmunity. Some researchers propose that CMV antibodies may cross-react with 21-hydroxylase – a key enzyme used by the adrenal glands to produce cortisol and aldosterone. This molecular mimicry could, in theory, lead to immune confusion, where the body starts attacking adrenal tissue as if it were viral in nature. While this mechanism is not yet confirmed by direct human studies, it offers a compelling explanation for why some individuals present with adrenal symptoms without classic autoimmune markers. This process may resemble the autoimmune pathway of Addison’s disease, even if classical tests do not reflect full adrenal failure.

When Tests Are Misleading: The ACTH-Cortisol Paradox

Most clinicians screen for adrenal insufficiency using blood levels of cortisol and ACTH (adrenocorticotropic hormone). However, in the presence of viral-induced immune activation, these markers can be misleading. Cytokines – chemical messengers released during chronic inflammation – can artificially elevate or suppress cortisol and ACTH without reflecting true adrenal gland function.

This means that someone may appear “normal” on a standard cortisol test, yet still suffer from classic symptoms of adrenal insufficiency due to viral interference or immune mimicry. This false-negative scenario is more common than many realize, especially in chronic fatigue states, fibromyalgia, and autoimmune overlap syndromes.

Symptoms That Often Go Unrecognized

Many of the symptoms associated with Addison’s disease or adrenal suppression are subtle but pervasive. These include:

Physiological Symptoms:

            •           Low blood pressure or dizziness when standing up

            •           Salt cravings

            •           Chronic fatigue unrelieved by rest

            •           Nausea or poor appetite

            •           Muscle weakness

            •           Darkening of the skin (hyperpigmentation)

Emotional & Cognitive Symptoms:

            •           Brain fog

            •           Low stress tolerance

            •           Anxiety or inner restlessness

            •           Depressive episodes

            •           Emotional detachment or apathy

These symptoms can easily be dismissed or attributed to “burnout” or stress, especially when lab markers are borderline or within so-called normal ranges.

The Gut-Adrenal-Immune Axis

Chronic viral infections don’t just impact the adrenal glands – they also affect gut health. Inflammatory cytokines produced during immune responses to stealth viruses can disrupt gut barrier integrity, leading to a leaky gut and increased susceptibility to gastrointestinal conditions.

This is why we often see overlapping diagnoses such as:

            •           IBD (Inflammatory Bowel Disease)

            •           Crohn’s Disease

            •           Ulcerative Colitis

            •           IBS (Irritable Bowel Syndrome)

Research has shown that stress hormones like cortisol normally play a protective role in gut barrier function. When cortisol is dysregulated due to immune mimicry or stealth viral interference, gut permeability increases. This sets up a vicious cycle where immune triggers in the gut further disrupt endocrine function – and vice versa.

A Precision Medicine Perspective

In conclusion, stealth viral infections such as CMV can have profound, far-reaching effects on the body – triggering autoimmune-like symptoms, confusing hormone signalling, and eroding gut health. Yet, because conventional testing often fails to detect these dynamics early on, many people are left misdiagnosed or untreated.

Precision medicine asks us to step back and look at the entire terrain. It is not enough to chase a single pathogen or treat an isolated lab result. We must understand the interplay between immune activation, hormonal feedback, gut health, and environmental exposures.

As Professor Naviaux notes in his Cell Danger Response theory, healing cannot happen when the body is stuck in a threat-based metabolic state. Dr. Klinghardt emphasizes terrain over germ, and Dr. Cheney reminds us that biological complexity requires multidimensional solutions.

Through this lens, restoring adrenal vitality isn’t just about giving hydrocortisone or boosting cortisol. It’s about addressing underlying stealth infections, calming immune chaos, repairing the gut lining, and gently guiding the body out of a defensive posture.

True recovery lies not in reductionism, but in integration. And it begins by asking the right questions – not just “What’s the diagnosis?” but rather, “What story is the body trying to tell?”

Medical Advice Disclaimer: This content is for educational purposes only and is not a substitute for professional medical advice. Always consult your healthcare provider for personalized medical care.

/0 Comments/by

Why We Crave Gluten: A Hidden Dialogue Between the Brain, Mitochondria, and the Immune System

Most people think of gluten cravings as simply a love for bread, pasta, or pastries. But behind this common desire may lie a far more complex conversation happening between the brain, the immune system, and our cells’ energy factories — the mitochondria. Emerging evidence suggests that gluten-rich foods might temporarily calm certain kinds of cellular “noise” in the nervous system, especially when energy metabolism or neurotransmitter balance is disrupted. This idea may also shed light on why gluten sensitivity, brain fog, and even aspects of neurodivergence — such as autism spectrum traits — often intersect in fascinating and sometimes confusing ways.

⸻

A Hypothesis: Gluten as a Short-Term Calming Signal

To understand the craving for gluten, it helps to first look at how the body regulates energy and stress at the cellular level. When cells are under pressure — from inflammation, oxidative stress, or poor mitochondrial efficiency — they tend to release a molecule called ATP into the space outside the cell. While ATP normally fuels the body from within, when released outside it acts as a danger signal, stimulating nearby immune and nerve cells and causing an inflammatory response. This phenomenon is known as purinergic signaling.

If the release of ATP becomes excessive, the system can enter a hyper-excitable state — nerves fire too readily, the immune system stays on alert, and sensations of anxiety, pain, or muscular tension may increase. The body naturally tries to balance this by converting ATP into adenosine, a calming molecule that suppresses inflammation and relaxes neural activity.

Here’s where gluten enters the picture. Gluten-derived peptides interact with an enzyme called DPP-4 (dipeptidyl-peptidase-4), which normally anchors another enzyme called adenosine deaminase (ADA). ADA’s job is to break down adenosine. When gluten interferes with DPP-4, ADA can’t do its job as efficiently — and adenosine levels rise.

That increase in adenosine may momentarily dampen the inflammatory and neural hyper-excitability caused by ATP release. In other words, gluten may provide a temporary biochemical “quieting” effect for some individuals whose nervous systems are overstimulated. The craving for gluten might therefore reflect not just habit, but a subconscious attempt to restore calm in an overactive cellular environment.

⸻

The Mitochondrial Connection: Dehydrogenase Activity and Energy Flow

But why would some people experience this hyper-excitability in the first place? One clue lies in the mitochondria — tiny power plants inside our cells that depend on a group of enzymes called dehydrogenases. These enzymes (such as PDH, α-ketoglutarate dehydrogenase, and succinate dehydrogenase) feed electrons into the electron transport chain (ETC) to make ATP.

When dehydrogenase function falters — whether due to nutrient deficiencies, oxidative stress, or inherited metabolic tendencies — the cell’s ability to produce clean energy drops. This leads to a buildup of partially oxidized metabolites like succinate, which can further drive inflammation through immune receptors such as SUCNR1. The body experiences this as a kind of internal “static”: energy demand increases while efficiency falls, triggering stress responses in both neurons and immune cells.

Under these conditions, the nervous system may release more ATP into the extracellular space, heightening purinergic signaling and inflammation. Gluten-induced adenosine accumulation might blunt this reaction — a biochemical coping mechanism for mitochondrial stress. This may help explain why gluten cravings can be especially strong in people who feel fatigued, anxious, or mentally overstimulated.

⸻

Serotonin, Dopamine, and Neurodivergence

Serotonin and dopamine — two key neurotransmitters — also play an intricate role in this balance. When mitochondrial efficiency declines, serotonin production in the gut and brain can drop, while dopamine pathways may become overactive.
• Serotonin generally acts as a paracrine calming molecule, modulating sensory and motor excitability and softening muscle tension through receptors found in peripheral tissues and sensory endings such as Pacinian and Ruffini corpuscles.
• Dopamine, on the other hand, amplifies neural firing and reward drive, enhancing sensitivity and sometimes increasing restlessness or impulsivity.

In neurodivergent states such as autism, this imbalance — reduced serotonin tone with heightened dopamine activity — is often documented. The body may seek ways to self-regulate, and consuming gluten could momentarily restore balance through its effects on adenosine signaling.

This doesn’t mean gluten is beneficial in the long term. Chronic activation of this pathway may calm inflammation but can also impair executive function, focus, and cognitive flexibility, all of which rely on finely tuned dopaminergic control. Thus, gluten cravings might represent a biochemical trade-off: relief from cellular overstimulation at the expense of mental clarity and long-term metabolic health.

⸻

Supporting the Transition Away from Gluten

For individuals who feel better reducing or eliminating gluten but struggle with cravings or withdrawal fatigue, addressing the underlying metabolic imbalance is essential. Supporting the dehydrogenase network helps restore efficient mitochondrial function, reducing the need for adenosine-based “chemical sedation.”

Key nutritional cofactors that aid this process include:
• Riboflavin (Vitamin B₂): Converts to FAD, a cofactor for succinate dehydrogenase and other flavoproteins in the ETC.
• Thiamine (Vitamin B₁): Crucial for pyruvate and α-ketoglutarate dehydrogenase activity.
• Niacin (Vitamin B₃): Replenishes NAD⁺, supporting redox balance and ATP synthesis.
• Lipoic acid: Recycles cofactors and reduces oxidative stress within dehydrogenase complexes.
• Magnesium and manganese: Support ATP stabilization and enzyme activity.
• Lithium (in trace nutritional form): Stabilizes mood and enhances mitochondrial resilience and neurogenesis.

Together, these nutrients can revitalize the cell’s energy network, reducing excess ATP release and calming purinergic overactivation naturally. When combined with adequate hydration, sunlight exposure, and gentle physical activity — which improve mitochondrial oxygen use — the body gradually regains balance without needing gluten’s biochemical “shortcut.”

⸻

In Summary

The craving for gluten may not just be psychological or cultural; it could represent the body’s instinctive attempt to modulate cellular stress. Gluten temporarily raises adenosine levels by interfering with enzymes that clear it, calming inflammation and neural excitability. Yet this soothing comes at the cost of executive function and long-term energy efficiency.

By improving mitochondrial dehydrogenase function and restoring serotonin–dopamine balance through proper nutrition, lifestyle support, and mindful dietary change, it becomes possible to quiet the body’s internal noise naturally — no gluten required. What begins as a craving can thus become a clue: a message from the mitochondria asking not for more wheat, but for more energy harmony.

/0 Comments/by