Zinc and Selenium

Zinc and selenium are essential trace elements. Zinc is a cofactor in over 300 enzymes and is needed for growth, immune function, wound healing, taste, vision and DNA synthesis. Selenium is incorporated into selenoproteins, including glutathione peroxidases, thioredoxin reductases and iodothyronine deiodinases, and has a role in antioxidant defence and thyroid hormone metabolism. Both are measured in serum or plasma, usually by inductively coupled plasma mass spectrometry or atomic absorption.

The tests identify deficiency in patients with malabsorption, parenteral nutrition, burns and chronic disease, and diagnose excess after supplement or occupational exposure. They are interpreted with the clinical context, inflammatory markers and albumin, since serum levels fall in acute inflammation without any change in body stores.

Zinc deficiency affects an estimated 17% of the world population, and mild deficiency is common in infants and young children in low income settings. Selenium deficiency occurs where soil selenium is low, notably in parts of China (Keshan disease and Kashin-Beck disease), and in patients on long term parenteral nutrition.

Indications. Persistent diarrhoea, failure to thrive, dermatitis around orifices and extremities, alopecia, delayed wound healing, loss of taste or smell, recurrent infection, malabsorption, short bowel syndrome, inflammatory bowel disease, bariatric surgery, cirrhosis, chronic kidney disease, parenteral nutrition monitoring, burns, sickle cell disease, cardiomyopathy in a low selenium region, hair or nail change after supplements, and unexplained anaemia or neutropenia (zinc excess causing copper deficiency).

Specimen. Serum or heparin plasma from a trace element tube (royal blue top) taken with a metal free needle, avoiding rubber stoppers. A fasting morning sample is preferred because zinc has a diurnal rhythm, and falls after a meal. Haemolysis falsely raises zinc, because red cells contain about 10 times the plasma concentration. Separate within 2 hours. Samples for selenium are stable for days at 2 to 8 °C.

Ranges are method specific, and local ranges take precedence. Conversion: zinc microg/dL multiplied by 0.153 gives micromol/L, and selenium microg/L multiplied by 0.0127 gives micromol/L.

Zinc. Range: 11 to 24 micromol/L (70 to 150 microg/dL). Lowered:

• Reduced intake or absorption: poor diet, vegetarian diet high in phytate, malabsorption, coeliac disease, inflammatory bowel disease, short bowel, bariatric surgery, pancreatic insufficiency, prolonged parenteral nutrition without zinc.
• Increased loss: chronic diarrhoea, burns, exudative skin disease, nephrotic syndrome, haemodialysis, diuretics, sickle cell disease.
• Redistribution: acute inflammation, infection, myocardial infarction, stress, pregnancy, oral contraceptives, low albumin (zinc is bound to albumin), and hypoalbuminaemia of any cause.
• Inherited: acrodermatitis enteropathica (SLC39A4 mutation), with periorificial and acral dermatitis, diarrhoea and alopecia in infants, and transient neonatal zinc deficiency in breastfed infants of mothers with low breast milk zinc.
• Also cirrhosis, alcohol use, chronic kidney disease, and drugs (penicillamine, valproate, thiazides, ACE inhibitors, chelators).

Raised: supplement excess, haemolysis in vitro, contaminated sample, and occupational exposure. Excess zinc (usually over 50 mg daily for months) causes copper deficiency with anaemia and neutropenia, nausea, and impaired immunity.

Zinc must be read with C-reactive protein and albumin. A low value with raised C-reactive protein or low albumin may reflect redistribution, and a low value with normal inflammatory markers and a compatible clinical picture supports true deficiency, which is confirmed by a response to supplements.

Selenium. Range: 0.8 to 1.5 micromol/L (60 to 120 microg/L) in plasma. Lowered:

• Inadequate intake in low selenium regions, long term parenteral nutrition without selenium, malabsorption, short bowel, bariatric surgery, dialysis, severe illness, and acute inflammation (falls with the acute phase response).
• Deficiency causes cardiomyopathy (Keshan disease), skeletal and joint disease (Kashin-Beck disease), skeletal muscle pain and weakness, macrocytosis, white nail beds, and impaired thyroid hormone conversion.
• Low selenium is a feature in autoimmune thyroid disease, and supplement benefit is limited and uncertain.

Raised: supplement excess, brazil nut intake, occupational exposure, contaminated water. Selenosis occurs at serum levels over 2.5 micromol/L (over 200 microg/L): garlic breath, metallic taste, brittle hair and nails with loss, skin rash, nausea, diarrhoea, irritability, peripheral neuropathy, and rarely acute respiratory failure and cardiac failure.

Zinc deficiency syndromes.

• Infants and children: growth failure, diarrhoea, recurrent infection, delayed puberty, erythematous eczematous dermatitis around the mouth, anus and acral skin.
• Adults: hypogeusia, hyposmia, delayed wound healing, hair loss, night blindness, mouth ulcers, impotence, and nail changes with white spots.
• Severe: acrodermatitis enteropathica pattern with low alkaline phosphatase (a zinc dependent enzyme) as a laboratory clue.

Response to supplement. Clinical improvement within 1 to 2 weeks (taste, skin, diarrhoea) and normalisation of serum zinc in weeks supports the diagnosis. Long term treatment needs monitoring of copper.

Selenium deficiency patterns. Cardiomyopathy with low plasma selenium in a low selenium region, or after prolonged parenteral nutrition, and low glutathione peroxidase activity. Repletion improves the condition, particularly cardiomyopathy and muscle symptoms.

Selenium excess. Garlic odour, hair and nail loss and neuropathy with plasma selenium over 2.5 micromol/L, and prompt resolution after stopping the supplement.

Critical values and findings needing immediate action. Triggers vary by laboratory.

• Zinc under 6 micromol/L with severe dermatitis, diarrhoea, poor wound healing or in an infant.
• Zinc over 40 micromol/L with symptoms, or a long supplement history with anaemia and neutropenia (copper deficiency).
• Selenium under 0.4 micromol/L in a patient on parenteral nutrition with cardiomyopathy or heart failure.
• Selenium over 3.0 micromol/L with neurological or gastrointestinal features.

Interferences and pitfalls.

• Serum zinc falls in the acute phase response, pregnancy, oral contraceptive use, after meals and in hypoalbuminaemia, so a low value in an acutely ill patient is interpreted with C-reactive protein and albumin.
• Haemolysis, a clotted sample, rubber stoppers and contaminated needles raise zinc falsely.
• Serum zinc poorly reflects tissue stores, and no test gives a perfect measure of status. Hair zinc and nail levels are not reliable.
• Plasma selenium reflects recent intake, whereas red cell selenium and glutathione peroxidase activity reflect longer term status.
• Selenium falls with inflammation, and the acute phase fall is not deficiency.
• Supplements, multivitamins and shampoos (selenium sulphide) contribute to levels.
• Excess zinc lowers copper, and the reverse can occur with other trace elements, so panels are better than single elements.
• Biotin does not interfere with elemental analysis.

Special groups.

• Neonates and infants: low zinc in preterm infants, and in exclusively breastfed infants of mothers with low breast milk zinc.
• Children: zinc supplementation is part of the treatment of acute diarrhoea in low income settings, and deficiency causes stunting.
• Pregnancy: serum zinc falls by about 20 to 30% and deficiency is associated with poor outcomes.
• Older adults: reduced intake, drug effects and malabsorption increase deficiency.
• Patients on parenteral nutrition: zinc and selenium losses are large in diarrhoea, fistulas and burns, and monitoring is needed every 3 to 6 months.
• Regions: selenium poor soil (parts of China, Tibet, New Zealand and parts of Europe) and zinc poor diets are common.

Follow up tests. C-reactive protein, albumin, alkaline phosphatase, copper and caeruloplasmin, full blood count, iron studies and ferritin, vitamin A and E levels, thyroid function tests, glutathione peroxidase activity, red cell selenium, echocardiography in suspected selenium cardiomyopathy, coeliac serology, faecal elastase, stool tests for diarrhoea, and dietary assessment.