Eczema, Psoriasis and Dermatitis: The Copper-Iron Axis in Inflamed Skin

The same systems that drive skin ageing run through atopic dermatitis (eczema), psoriasis and other forms of dermatitis, with one difference: inflammation shifts the blood markers, so they need reading with even more care. The mechanisms (copper, iron, mitochondria, endothelin-1, nitric oxide and sunlight) are set out in Skin Longevity From the Inside Out; pigmentation after flares is covered in Pigmentation and Melasma.

Sunlight and vitamin D

• UVB is already a standard treatment. In a Finnish study, 89% of psoriasis patients and 94% of atopic dermatitis patients were vitamin D insufficient at the start of winter. Fifteen narrowband UVB sessions raised 25(OH)D by 60–68 nmol/L and significantly improved both PASI and SCORAD scores. In the lesions, the antimicrobial peptide cathelicidin rose further while human β-defensin 2 fell (Vähävihu 2010). The skin improvement did not track the rise in blood vitamin D, so UVB works through local skin effects as well as vitamin D.
• Low-dose UVB strengthens the barrier. Suberythemal UVB (about half a burning dose, daily for three days) accelerated barrier recovery and raised filaggrin, involucrin and the skin's antimicrobial peptides; blocking the skin's vitamin D activation abolished these benefits (Hong 2008).
• Oral vitamin D in eczema. The most recent meta-analysis of randomised trials found that vitamin D supplementation reduced atopic dermatitis severity in children and adults (Nielsen 2024); an earlier analysis found about 1,600 IU a day produced a clinically meaningful reduction (Hattangdi-Haridas 2019). Not every analysis agrees: one 2023 meta-analysis found no significant SCORAD reduction (PMC10079516). These trials used supplements; this post's approach is to correct low vitamin D through sunlight (or the UVB phototherapy dermatology already uses) and cod liver oil instead.

ET-1: plaques and itch

• Psoriasis. ET-1 was raised in the blood and in lesional skin of psoriasis patients, and both levels correlated with disease severity (PASI) (Bonifati 1998). Psoriatic keratinocytes make ET-1, which suppresses their normal cell death, and inflammation drives more ET-1 production, a loop that keeps keratinocytes proliferating (Borska 2017).
• Itch. ET-1 is a potent itch trigger in humans that works partly independently of histamine, which helps explain why antihistamines often fail in chronic itch. The ET-1 pathway was upregulated in human chronic-itch skin, and blocking the ET-A receptor reduced itch in mice with eczema-like skin (Kido-Nakahara 2014).
• Histamine and copper. Histamine is broken down by diamine oxidase (DAO), a copper enzyme. In rats, a merely marginal copper intake cut plasma DAO activity by 94%, more than any other marker measured (Kehoe 2000); in people, DAO was low in spontaneous copper deficiency and rose with copper repletion (DiSilvestro 1997). Copper-deficient rats also had about 50% more mast cells, the cells that store histamine, with greater histamine-driven leakage from small vessels (Schuschke 1994). In eczema, a subgroup of patients had higher plasma histamine and reduced DAO activity, and a histamine-free diet reduced their eczema severity (Maintz 2006); in another study, plasma histamine was higher in eczema and a third of patients improved on a histamine-free diet, though DAO activity there was similar to controls (Worm 2009). So itch has two arms that a copper shortfall can push: more histamine, from slower breakdown and more mast cells, and more ET-1, from the oxidative stress of the copper–iron axis. Antihistamines block only the first. I have not found a study measuring copper status alongside DAO in people with eczema; that is the study needed.
• Nitric oxide. Serum nitric oxide is also raised in psoriasis and tracks severity (Kalaycı). In inflamed skin, rich in superoxide, that nitric oxide feeds the peroxynitrite loop described in the skin longevity post.

Mitochondrial dysfunction in inflamed skin

In both psoriasis and eczema, mitochondria in skin cells are damaged by the inflammation and then feed it.

• Psoriasis: damaged mitochondria in plaques, mitochondrial DNA in the blood. Lesional psoriatic skin showed lower expression of the mitochondrial regulators UCP2 and Drp1 than non-lesional or healthy skin, and patients had more mitochondrial DNA circulating in their serum, which acts as an inflammatory danger signal (Therianou 2019).
• Psoriasis cytokines break mitochondria. In human keratinocytes and fibroblasts, the psoriasis cytokines IL-17A, IL-22 and TNF-α raised mitochondrial ROS, suppressed respiration, fragmented the mitochondrial network and dissolved the cristae, the folds where the electron transport chain sits; keratinocytes were hit faster and harder (Kulkoviene 2025, FEBS J).
• Mitochondrial ROS drive plaque growth. IL-17A switched on mitochondrial ROS and HIF1α in human keratinocytes, driving their overgrowth; both were raised in patients' epidermis, and blocking ROS reversed the keratinocyte overgrowth (J Immunol 2024).
• Eczema: fewer mitochondrial proteins, weaker antioxidant defence. Proteomics of patients' epidermis showed reduced mitochondrial proteins in key metabolic pathways and impaired NRF2, the master antioxidant switch; the two were partly linked (Koch 2023, JID).
• Eczema: oxidative stress even in clear skin. Keratinocytes from non-lesional eczema skin showed raised mitochondrial activity and oxidative stress, and a mitochondria-targeted antioxidant largely corrected the eczema profile in lab-grown epidermis, including inflammatory signalling and abnormal barrier lipid bodies (JID 2022).

This connects to the rest of the copper–iron picture: a copper-short Complex IV leaks superoxide, free iron turns it into hydroxyl radicals, and in inflamed skin full of nitric oxide, superoxide becomes peroxynitrite. Copper, retinol and magnesium, which keep the electron transport chain working, are covered in the skin longevity post. No trial has yet tested whether correcting them changes psoriasis or eczema.

Copper, zinc, iron and selenium: read through inflammation

A 2025 meta-analysis of 113 studies and 7,014 patients found serum zinc lower in psoriasis, serum copper higher in psoriasis and atopic dermatitis, and serum iron and selenium lower in both (Shao 2025); an earlier psoriasis meta-analysis found the same copper-up, zinc-down pattern (Lei 2019).

• Raised serum copper is not copper excess. Ceruloplasmin is an acute-phase protein, so inflammation pushes serum copper up; it can hide a working-copper shortfall rather than show an overload. Ceruloplasmin oxidase activity, read with CRP, tells you more.
• Low serum iron is often iron trapped in storage. Inflammation locks iron away, so low serum iron with normal or high ferritin points to inflammation, not simple deficiency. Check ferritin both ways, with CRP and transferrin saturation.
• Low zinc should be corrected through food first. High-dose zinc displaces copper.
• Low selenium is not a reason to supplement. Selenium has a narrow window between enough and too much. In a randomised trial of 1,202 people from dermatology clinics, 200 µg of selenium daily for an average of 7.7 years raised the incidence of type 2 diabetes by about 50% compared with placebo, and the risk was highest in those who started with the highest blood selenium (Stranges 2007). As with zinc, get it from food: fish and shellfish, eggs, meat and offal are the main sources, and Brazil nuts are so concentrated, about 68–91 µg per nut, that they are best eaten only occasionally. Supplementation belongs only in medically confirmed deficiency, under supervision.

Magnesium

Volunteers with atopic dry skin who soaked one forearm in a 5% magnesium-rich Dead Sea salt solution for 15 minutes daily had better barrier function (in those with a leaky barrier at baseline), more skin hydration and less roughness and redness than the tap-water arm; the authors attributed the effect mainly to magnesium (Proksch 2005). In a double-blind psoriasis study, Dead Sea salt baths reduced PASI by 34% at three weeks against 27% for common salt (Halevy 1997, reviewed).

Pigmentation after flares

Eczema, psoriasis and contact dermatitis commonly leave post-inflammatory hyperpigmentation as they settle, as inflammatory mediators activate melanocytes; it is more marked and longer-lasting in darker skin types, and UV exposure makes it worse (Kaufman 2018; Mar 2024). Atopic hyperpigmentation of the neck affected 14.3% of Asian patients with atopic dermatitis (Kaufman 2018). In psoriasis, plaques can clear in weeks while the pigment change lasts for years, so the most effective prevention is controlling the inflammation itself (Gelfand, Healio). ET-1 is raised in psoriatic skin and drives melanocytes through the ET-B receptor, a plausible link; whether ET-1 drives pigmentation after flares has not been tested.

What this means in practice

Alongside medical treatment, not instead of it:

• Test vitamin D (25(OH)D and active 1,25-dihydroxyvitamin D) with PTH and calcium, ferritin with transferrin saturation and CRP, copper with ceruloplasmin activity, zinc and RBC magnesium, and read every result against the inflammation.
• Get regular, moderate, non-burning sunlight, the natural form of the UVB that dermatology already prescribes.
• Correct low vitamin D through sunlight and cod liver oil.
• Use magnesium-rich bath salts for barrier support.
• Correct low zinc and selenium with food rather than supplements.

References

Sunlight and vitamin D

• Vähävihu K et al. Narrowband ultraviolet B treatment improves vitamin D balance and alters antimicrobial peptide expression in skin lesions of psoriasis and atopic dermatitis. Br J Dermatol 2010. Link
• Hong SP et al. Biopositive effects of low-dose UVB on epidermis: coordinate upregulation of antimicrobial peptides and permeability barrier reinforcement. J Invest Dermatol 2008. Link
• Nielsen AY et al. Vitamin D supplementation for treating atopic dermatitis in children and adults: systematic review and meta-analysis. Nutrients 2024. Link
• Hattangdi-Haridas SR et al. Vitamin D deficiency and effects of vitamin D supplementation on disease severity in atopic dermatitis: systematic review and meta-analysis. Nutrients 2019. Link
• Effect of vitamin D on the treatment of atopic dermatitis with consideration of heterogeneities: meta-analysis of randomized controlled trials. 2023. Link

ET-1 and nitric oxide

• Bonifati C et al. Endothelin-1 levels are increased in sera and lesional skin extracts of psoriatic patients and correlate with disease severity. Acta Derm Venereol 1998. Link
• Borska L et al. Roles of miR-31 and endothelin-1 in psoriasis vulgaris. Physiol Res 2017. Link
• Kido-Nakahara M et al. Neural peptidase endothelin-converting enzyme 1 regulates endothelin 1–induced pruritus. J Clin Invest 2014. Link
• Kalaycı BN, Doğan G. The relationship between serum endothelin-1 and nitric oxide levels and severity of psoriasis. Türkiye Klinikleri. Link
• Kehoe CA et al. Plasma diamine oxidase activity is greater in copper-adequate than copper-marginal or copper-deficient rats. J Nutr 2000. Link
• DiSilvestro RA et al. Plasma diamine oxidase activities in renal dialysis patients, a human with spontaneous copper deficiency and marginally copper deficient rats. Clin Biochem 1997. Link
• Schuschke DA et al. Dietary copper deficiency increases the mast cell population of the rat. Proc Soc Exp Biol Med 1994. Link
• Maintz L et al. Evidence for a reduced histamine degradation capacity in a subgroup of patients with atopic eczema. J Allergy Clin Immunol 2006. Link
• Worm M et al. Exogenous histamine aggravates eczema in a subgroup of patients with atopic dermatitis. Acta Derm Venereol 2009. Link

Mitochondrial dysfunction

• Therianou A et al. Mitochondrial dysfunction in affected skin and increased mitochondrial DNA in serum from patients with psoriasis. Exp Dermatol 2019. Link
• Kulkoviene G et al. Psoriasis-like inflammation induces structural and functional changes in mitochondria. FEBS J 2025. Link
• IL-17A orchestrates reactive oxygen species/HIF1α-mediated metabolic reprogramming in psoriasis. J Immunol 2024. Link
• Koch M et al. Quantitative proteomics identifies reduced NRF2 activity and mitochondrial dysfunction in atopic dermatitis. J Invest Dermatol 2023. Link
• Mitochondrial dysfunction and oxidative stress in nonlesional atopic dermatitis keratinocytes. J Invest Dermatol 2022;142(10). Link

Copper, zinc, iron and selenium

• Shao X et al. Trace elements and risk of immune-mediated skin disease: systematic review and meta-analysis. Nutr Rev 2025. Link
• Lei L et al. Abnormal serum copper and zinc levels in patients with psoriasis: a meta-analysis. Indian J Dermatol 2019. Link
• Stranges S et al. Effects of long-term selenium supplementation on the incidence of type 2 diabetes: a randomized trial. Ann Intern Med 2007. Link

Magnesium

• Proksch E et al. Bathing in a magnesium-rich Dead Sea salt solution improves skin barrier function, enhances skin hydration, and reduces inflammation in atopic dry skin. Int J Dermatol 2005. Link
• Halevy S et al. Dead Sea bath salt for the treatment of psoriasis vulgaris: a double-blind controlled study. J Eur Acad Dermatol Venereol 1997 (reviewed). Link

Pigmentation after flares

• Kaufman BP et al. Postinflammatory hyperpigmentation: epidemiology, clinical presentation, pathogenesis and treatment. Am J Clin Dermatol 2018. Link
• Mar K et al. Treatment of post-inflammatory hyperpigmentation in skin of colour: a systematic review. J Cutan Med Surg 2024. Link
• Gelfand JM. Progress needed in treating patients with skin of color and psoriasis. Healio 2021. Link