Selenium is essential for a healthy immune system, thyroid metabolism and is a component of the antioxidant enzyme glutathione peroxidase (GPx). It is present in grains such as rice and wheat, and nuts (especially Brazil nuts), seafood, and meat. The soil in parts of New Zealand, China and Finland are notably selenium deficient and this is reflected in lower selenium concentrations in blood and urine in these populations. Soil concentrations are lower in Europe and since the UK population obtains its wheat from Europe, plasma concentrations tend to be lower than elsewhere. An unusual form of cardiomyopathy (Keshan Disease) was found to be endemic in an area of China and has now been prevented by prophylactic administration of supplemental selenite.
There is no homeostatic control of GI absorption and around 50% of ingested selenium is absorbed depending on the chemical form and its solubility. Regulation of body content is primarily by urinary excretion. The urinary output of selenium therefore reflects recent dietary supply and the form of Se in the diet: selenate for example is rapidly absorbed but then most is excreted rapidly in the urine. In extreme selenium deficiency urine excretion is very low. Selenium in plasma is associated with selenoprotein P (50 - 60%), GPx (30%) and albumin (9%).55
Selenocysteine is the biologically active form and is involved in the active site of several enzymes involved in oxidation-reduction reactions. There is persuasive evidence suggesting that selenium concentrations above normal UK reference intervals help protect against oxidant stress, improve immuno-responsiveness and lower overall risk of cancer.56
Selenium status can be assessed by measurement of plasma selenium, which responds to changes in intake. It is, however, subject to the systemic inflammatory response which lowers the concentration by up to 60% following a trauma (Table 1).27 This reduction is dependent on the magnitude of the systemic inflammatory response (Table 2).28 Measurement of the selenoprotein GPx provides an alternative functional test for selenium status (test no longer available at STEMDRL). At relatively low intakes of selenium, plasma concentrations correlate with GPx until this plateaus. It responds more slowly than selenium to changes in intake and is not subject to systemic inflammatory response. Red cell selenium concentrations are also a useful guide to status. However, red cell concentrations have a half-life of around two months (similar to the half-life of red cells) and so do not give an indication of recent deficiency.57
We recommend that plasma and red cell selenium are measured to assess selenium status in patients. Plasma selenium is a short term marker, but is not valid when CRP >10 mg/L. Red cell selenium is a long term marker that is not affected by the systemic inflammatory response.
Deficiency only rarely causes overt clinical signs and symptoms such as muscle weaknes, pain and cardiomyopathy. In the absence of guidelines on when patients should be supplemented, we suggest this is appropriate in adults with plasma selenium of less than 0.6 µmol/L assuming there is no systemic inflammatory response or when the red cell selenium is less than 3 nmol/g haemoglobin. The UK National Diet and Nutrition Survey showed that over 65 year olds have a lower plasma selenium concentration (0.66 – 1.6 µmol/L).58 Since this may represent poorer nutrition associated with this population group we do not quote this as a specific reference interval.
Selenium toxicity is only found in selenium workers and may present with skin eruptions, gastrointestinal upset, hair and nail changes, and discoloration of teeth.
Recommended Daily Allowance
Males: 75 µg/day, Females: 60 µg/day. These are concentrations which should result in plasma selenium concentrations of 0.95 µmol/L which is thought to equate to maximum GPx activity in plasma.
Effect of Systemic Inflammatory Response on Plasma & Red Cell Selenium Concentrations
Table 1: Baseline, peak/ trough and day 7 concentrations of CRP and plasma & red cell selenium following elective surgery for knee arthroplasty (n = 20).27
|CRP (mg/L)||<6 (<6–17)||160 (83–240)||29(10–87)||<0.001|
|Plasma selenium (μmol/L)||0.89 (0.79-1.14)||0.66 (0.51-0.80)||0.87 (0.66-1.01)||<0.001|
|Red cell selenium (μmol/mmol Fe)||84 (69-136)||82||85.7 (66-135)||0.1|
Table 2: Distribution of median plasma selenium concentrations according to increments of CRP concentrations (n = 2083).28
Median plasma selenium concentration
Sample Requirements and Reference Ranges for Selenium
|Sample Type||Plasma / serum and red cells (fasting sample preferred)|
|Container||Lithium heparin (non-gel), plain, or ‘Trace Metal’.|
Plasma/serum/red cells: Send whole blood by 1st class post within 72 hours (do not freeze whole blood).
If delivery to Glasgow is outwith 72 hours of sample collection, prepare red cells (minimum volume 150 µL) by removing plasma and buffy layer (mark clearly on tube that they are red cells) and store frozen until sending and then send both plasma and red cells by first class post (ice or dry ice not required). Lithium heparin gel tubes are unsuitable.
Plasma: 250 µL* (copper and zinc can be analysed simultaneously)
Red cells: 100 µL*
Plasma: 0.75–1.50 µmol/L (Adults aged 17 years and over)58
> 2.50 µmol/L (in adult) possible toxicity
0.20 - 0.90 µmol/L (0 to 2 years)59
0.50 - 1.30 µmol/L (3 to 4 years)59
0.70 - 1.70 µmol/L (5 to 16 years)59
Red cells: 3.0 - 9.0 nmol/g haemoglobin (STEMDRL derived)
|Mean turnaround time||Plasma: 2.6 days|
|Method||Inductively coupled plasma mass spectrometry|
Plasma: Traceable to reference material produced in accordance with EN ISO 17511:2003 “In vitro diagnostic medical devices. Measurement of quantities in biological samples. Metrological traceability of values assigned to calibrators and control materials”.
Red Cell: Not currently traceable. Trueness validated using whole blood reference material produced in accordance with EN ISO 17511:2003 “In vitro diagnostic medical devices. Measurement of quantities in biological samples. Metrological traceability of values assigned to calibrators and control materials”.
|Intermediate Precision (CV)||
Plasma: 3.0% at 0.9 µmol/L, 2.4% at 1.9 µmol/L
Red Cell: 3.7% at 3.55 nmol/g Hb
|Measurement Uncertainty, U||
Plasma: 1.1 ± 0.07 µmol/L, 1.7 ± 0.09 µmol/L
Red cell: 8.1 ± 0.70 nmol/g Hb
|Analytical Goals (CV)||
Plasma: Acceptable 9.0%, Desirable 6.0%**
Red Cell: 8%***
Plasma: UK NEQAS, Guildford (once per month).
Red cell: UK NEQAS, Guildford (whole blood EQA scheme, once per month).
*Absolute minimum volume; this volume is insufficient to carry out repeat analysis if analysis fails.
**Goal origin: biological variation32 ***Goal origin: STEMDRL state-of-the-art