N05012: Functional markers of selenium in man
Thursday 3 April 2003
This research project aims to give an insight into the effects of selenium supplementation and contribute to the debate as to whether selenium status should be increased in the UK in order to promote optimal health.
Background
Previous biochemical studies have suggested that there is a relative lack of selenium in the UK diet although the effect of this on selenium-dependent functions is unclear. Groups of subjects with relatively low serum selenium concentrations (<1.0 mircomoles per litre) will receive either placebo, 50 or 100 mircograms selenium per day (as NaSeO4) and the possible effects of this on two potential key functions of selenium: the maintenance of immune function, and the mutation rate of an RNA virus (studied by examining the rate of mutation of a live attenuated rotavirus vaccine administered to the subjects) will be examined. These will be examined in parallel with a stable isotope study to determine the key functional pool of selenium, the selenite exchangeable pool, in these subjects.
These data will be important to understanding the functional effects of the apparent lack of selenium in the UK diet and may identify appropriate functional markers of selenium status.
Research Approach
A large group of healthy volunteers were screened and 60 subjects with low Se plasma concentrations were recruited. Subjects were randomly allocated to one of three groups of 20 subject to receive either placebo, 50 or 100 mircograms per day of sodium selenite for 6 weeks prior to commencement of studies. Previous data indicate that 50 mircograms per day will increase the activity of some selenium dependent enzymes in a similar population, but that a plateau of activity will not be achieved for some enzymes. Subjects remained on the placebo or supplement until the end of the viral and isotope studies.
Subjects were given an oral dose of rotavirus vaccine. Faecal samples were collected at intervals after inoculation and processed for rotavirus RT-PCR. PRC product from each final positive sample was then sequenced by automated sequencing. The influence of selenium status on the rate of mutation of RNA viruses was investigated.
Blood samples were collected at intervals after inoculation with the oral vaccine. Both the antibody response and the cellular response were determined.
Following a 24-hour baseline urine collection an intravenous dose of selenite was administered, and urine collection continued for 14 successive days commencing 24 hours following isotope infusion. Total urinary Se excretion was calculated.
Serum selenium concentrations and glutathione peroxidase and phospholipid peroxidase activities in granulocytes and lymphocytes were calculated.
Results and findings
Background
Dietary selenium intake has fallen in the UK and other northern European countries for about 25 years, but no functional consequences of this have been apparent. Data obtained from epidemiological studies in a number of countries support an increased risk of cardiovascular disease or cancer as a potential consequence of a relative lack of selenium.
One possible mechanism by which a relative lack of selenium might influence health is through compromising immune function. Indeed, previously published studies using animal models suggest that marginal intakes of selenium lead to diminished immunity and increased rate of mutation of certain viruses.
Previous work undertaken in Aberdeen by Professor Arthur indicated that UK subjects, who were given small selenium supplements (50 µg/day for 6 weeks), responded by biochemical changes in the activity of certain enzymes in the blood that require selenium for their normal function. However, no evidence had been presented that the relative lack of selenium had any functional consequences for health.
Rationale and Objectives
We reasoned that apparently healthy subjects in the UK who had relatively low selenium levels might show functional deficits in immunity and an increased rate of mutation of certain viruses in common with animals depleted of this nutrient. Furthermore, we wished to attempt to correlate potential deficits in immune function with biochemical markers of body selenium content and to determine whether small additional oral doses of selenium might correct these putative changes.
Our overall objective in the study was to examine, in apparently healthy UK subjects, the possible effects of small selenium supplements on two potential key functions of selenium: the maintenance of immune function and the mutation rate of a specific virus (which would be administered in a non-pathogenic form). These would be examined in parallel with a study to measure the total body content of selenium in the subjects.
Approach
The following approach was undertaken:
- We identified a group of 60 normal subjects from the Merseyside area with relatively low blood selenium concentrations and allocated them to groups of 20 that received either 50 or 100µg of selenium (as sodium selenite) or an identical placebo for 15 weeks.
- A specific type of virus vaccine was administered to all subjects. Poliomyelitis vaccine was used. This is a modified live virus which works by multiplication within the gastrointestinal tract, stimulating an immune response.
- The activity of specific parts of the immune system was examined in blood cells from subjects that were re-challenged with the poliomyelitis virus.
- Each subject was injected with a non-radioactive selenium isotope and the total body selenium content was calculated from the dilution of the isotope.
Outcome/Key results obtained
The data obtained indicate that supplementation with 50 or 100µg selenium per day was accompanied by significant improvements in a variety of measures of cellular immune status and in more rapid clearance of an administered, modified poliomyelitis virus.
Additionally, data on the size of body pools of selenium calculated following administration of the isotope, suggest that the beneficial effects observed may not be maximal at these doses and that subjects might benefit from even greater amounts of supplementary selenium.
What it means and why it is important
These data appear to be important for evaluation of the appropriate dietary selenium intake in the UK and other northern European countries. Survey data indicate that average UK dietary intakes are 29-39 µg/day and the currently recommended intake in the UK is 75 µg/day for adult males and 60 µg/day for adult females. A recent survey of plasma selenium concentrations in over 1000 elderly UK subjects indicated that the mean was 0.9 µmol/l, similar to the group studied here. Brief dietary histories of our subjects indicated that they are likely to have regular dietary intakes close to the UK average. Our data suggest that an increase in intake of at least 100 µg/day is warranted to optimise immune function and the isotope dilution data suggest that the additional 100 µg/day did not saturate body pools. However, caution is required in recommending an increase in selenium intake through supplements since the safe range of intake for selenium is relatively small with toxicity symptoms reported at intakes as low as 500 µg/day.
Dissemination information
Final report is available from the FSA Library and Information centre. To obtain a copy, please contact the Enquiry Desk, Dr Elsie Widdowson Library and Information Services, Food Standards Agency (Tel: 020 7276 8181/8182 or by e-mail to: infocentre@foodstandards.gsi.gov.uk ).