N05031: Assessment of individual variability in functional responses to Selenium

Study Duration: November 2001 to April 2003

Contractor: University of Liverpool

An appropriate supply of dietary selenium is essential for maintenance of health, but the selenium intake in the UK has fallen by up to 50% in the last 20 years. The functional effects of this are not clear and previous data indicate that increasing the intake leads to a variable response. It has been argued that a decline in selenium intake may have contributed to a decline in immune status, an increase in cancer risk and other adverse health effects. The situation in the elderly may be more marked. Although few studies have been carried out, elderly subjects in other European countries have been reported to have low selenium intakes and to respond to an increased selenium intake by changes in immune and thyroid status. Individual requirements for dietary selenium have not been defined, but some data indicate there may be an unexplained wide variability in biochemical responses of UK subjects to small supplemental doses of selenium.

This project will apply cDNA expression array technology to existing lymphocyte samples from healthy adults and elderly subjects taking differing levels of selenium. It will examine whether the variability of response is apparent in a wide range of indicators of immune status and determine whether subjects vary in their susceptibility to toxic effects of the selenium supplements.

Using existing samples from two intervention studies that examined the effects of low level supplementation with sodium selenite, the natural variabililty in selenium-dependent responses in the immune system and in the level at which early toxic responses may occur Iymphocytes from individual adult and elderly subjects, will be assessed.

It is likely that the variability in response of the immune system to selenium will be reflected in the expression and activity of cytokine networks following stimulation of lymphocytes. This project will utilise state-of-the-art cDNA arrays to determine the expression of a large number of cytokine and cytokine-associated genes in samples from subjects following different levels of selenium intake. Individual variability in the susceptibility of subjects to selenium toxicity might also underlie some of the reported differences in selenium responses and evidence of toxic effects will be obtained by increased expression of stress genes by lymphocytes. The cDNA arrays will be used to examine the expression of a wide range of stress effectors in the same subjects following different levels of selenium intake.

RNA was extracted from blood samples obtained in a previous FSA-funded study (N05012) and from ten elderly subjects, and analysed to determine the pattern of expression of multiple genes involved in either the immune response (>250 genes) or in the stress responses (>200 genes) of cells.

The data obtained indicated that overall the supplementation of adult subjects with selenium for 15 weeks caused a relatively minor increase in the expression of genes involved in the immune response, but that there was a substantial inter-individual variability in the magnitude of responses. Furthermore it appeared that some subjects always responded more dramatically than the rest of the group in a particular manner. Comparisons of these new data with previous analyses suggested that the subjects who responded atypically may have differed from the rest of the group in their pre-supplementation selenium levels. The studies of elderly subjects revealed that, compared to adult subjects, they had a greatly reduced increase in the expression of genes involved in the immune response following stimulation. There was, however, little evidence of a large between-subject variability in the elderly subjects.

These findings demonstrate that small selenium supplements increase multiple markers of immune status in apparently healthy subjects, but also indicate that some individuals may have more dramatic responses than others. They have also provided the first indication that these atypical subjects may be identified prior to supplementation by examining their pre-supplementation levels of an enzyme that requires selenium for its normal activity. The results also show that elderly subjects have a reduced ability to mount an immune defence following stimulation and indicate that selenium supplementation did not reverse this. Finally, the data indicate that the highest dose of selenium supplement used (100 micrograms/day) may have induced some minor stress in white blood cells.

The final report is available from the Agency's Information Centre.
To obtain a copy, please contact the Enquiry Desk, Information Services, Food Standards Agency (tel: 020 7276 8181/8182 or email: infocentre@foodstandards.gsi.gov.uk)

Contact: For any enquiries concerning this research project, please contact the relevant Programme contact or email: science@foodstandards.gsi.gov.uk