Search PubMed⌕ Search

Biomedical subjects

Margaret P Rayman

Publications and source records attributed to Margaret P Rayman.

5 recordsLinked to original sources

Selenium in cancer prevention: a review of the evidence and mechanism of action.

Se is an unusual trace element in having its own codon in mRNA that specifies its insertion into selenoproteins as selenocysteine (SeCys), by means of a mechanism requiring a large SeCys-insertion complex. This exacting insertion machinery for selenoprotein production has implications for the Se requirements for cancer prevention. If Se may protect against cancer, an adequate intake of Se is desirable. However, the level of intake in Europe and some parts of the world is not adequate for full expression of protective selenoproteins. The evidence for Se as a cancer preventive agent includes that from geographic, animal, prospective and intervention studies. Newly-published prospective studies on oesophageal, gastric-cardia and lung cancer have reinforced previous evidence, which is particularly strong for prostate cancer. Interventions with Se have shown benefit in reducing the risk of cancer incidence and mortality in all cancers combined, and specifically in liver, prostate, colo-rectal and lung cancers. The effect seems to be strongest in those individuals with the lowest Se status. As the level of Se that appears to be required for optimal effect is higher than that previously understood to be required to maximise the activity of selenoenzymes, the question has been raised as to whether selenoproteins are involved in the anti-cancer process. However, recent evidence showing an association between Se, reduction of DNA damage and oxidative stress together with data showing an effect of selenoprotein genotype on cancer risk implies that selenoproteins are indeed implicated. The likelihood of simultaneous and consecutive effects at different cancer stages still allows an important role for anti-cancer Se metabolites such as methyl selenol formed from gamma-glutamyl-selenomethyl-SeCys and selenomethyl-SeCys, components identified in certain plants and Se-enriched yeast that have anti-cancer effects. There is some evidence that Se may affect not only cancer risk but also progression and metastasis. Current primary and secondary prevention trials of Se are underway in the USA, including the Selenium and Vitamin E Cancer Prevention Trial (SELECT) relating to prostate cancer, although a large European trial is still desirable given the likelihood of a stronger effect in populations of lower Se status.

Anticarcinogenic Agents↗

The use of high-selenium yeast to raise selenium status: how does it measure up?

Selenium-enriched yeast (Se-yeast) is a common form of Se used to supplement the dietary intake of this important trace mineral. However, its availability within the European Union is under threat, owing to concerns expressed by the European Community (EC) Scientific Committee on Food that Se-yeast supplements are poorly characterised and could potentially cause the build up of Se in tissues to toxic levels. The present review examines the validity of these concerns. Diagrams of the biosynthesis and metabolism of Se compounds show which species can be expected to occur in Se-yeast preparations. Se-yeast manufacture is described together with quality-control measures applied by reputable manufacturers. The way in which speciation of Se-yeast is achieved is explained and results on amounts of Se species in various commercial products are tabulated. In all cases described, selenomethionine is the largest single species, accounting for 54-74 % of total Se. Se-yeast is capable of increasing the activity of the selenoenzymes and its bioavailability has been found to be higher than that of inorganic Se sources in all but one study. Intervention studies with Se-yeast have shown the benefit of this form in cancer prevention, on the immune response and on HIV infection. Of about one dozen supplementation studies, none has shown evidence of toxicity even up to an intake level of 800 microg Se/d over a period of years. It is concluded that Se-yeast from reputable manufacturers is adequately characterised, of reproducible quality, and that there is no evidence of toxicity even at levels far above the EC tolerable upper intake level of 300 microg/d.

Biological Availability↗

Low selenium status is associated with the occurrence of the pregnancy disease preeclampsia in women from the United Kingdom.

OBJECTIVE: Because the trace element selenium behaves as an antioxidant and peroxynitrite scavenger when incorporated into selenoproteins, our objective was to determine whether low selenium status was associated with a greater risk of occurrence of preeclampsia. STUDY DESIGN: Fifty-three preeclamptic patients and 53 matched pregnant controls at the John Radcliffe Hospital, Oxford, gave clippings of their toenails (laid down from 3-12 months previously) for selenium determination by neutron activation analysis. Clinical characteristics of the women and their infants were recorded. Statistical analysis was by Wilcoxon signed rank test and odds ratios were calculated by the ratio of discordant pairs. RESULTS: Median toenail selenium concentrations in the preeclamptic subjects were significantly lower than in their matched controls (P=.001). Being in the bottom tertile of toenail selenium was associated with a 4.4-fold (95% CI 1.6-14.9) greater incidence of the condition. Within the preeclamptic group, lower selenium status was significantly associated (P=.029) with more severe expression of disease, as measured by delivery before 32 weeks. CONCLUSION: In the light of the reduction in selenium status in a number of European countries in recent years, this study raises the question of whether a small increase in selenium intake might help prevent preeclampsia in susceptible women.

Adult↗

Abnormal iron parameters in the pregnancy syndrome preeclampsia.

OBJECTIVE: Our purpose was to investigate iron status parameters in preeclampsia with a view to exploring their possible contribution to the etiology. STUDY DESIGN: In prepared serum samples from 40 preeclamptic women and matched pregnant control subjects at the John Radcliffe Hospital, Oxford, a number of iron status parameters were measured. Statistical analysis was by the Wilcoxon signed rank test and linear regression. RESULTS: Serum iron concentration, ferritin, and percent saturation of transferrin were significantly higher in the preeclamptic patients than in control subjects, whereas unsaturated iron-binding capacity and apotransferrin levels were significantly lower. No difference was found in hemopexin concentrations in the two groups. Gestational age at the time of sampling was correlated (positively) with only two parameters, total and unsaturated iron-binding capacity, but only in the preeclampsia group. Eighteen percent of preeclamptic subjects had percent transferrin saturation levels in the region associated with iron overload. CONCLUSION: Released iron species in preeclampsia may contribute to the etiology and will exacerbate lipid peroxidation and endothelial cell injury. Given the high prevalence of heterozygosity for hemochromatosis with the associated reduced ability to exclude ingested iron, it would seem inadvisable, in the absence of evidence of iron deficiency, to give iron supplements to pregnant women at high risk for preeclampsia.

Apoproteins↗

The argument for increasing selenium intake.

The essential trace mineral, Se, is of fundamental importance to human health. As a constituent of selenoproteins it plays both structural and enzymic roles, in the latter context being best known as an antioxidant and catalyst for the production of active thyroid hormone. While Se-deficiency diseases have been recognised for some time, evidence is mounting that less-overt deficiency can also cause adverse health effects and furthermore, that supra-nutritional levels of Se may give additional protection from disease. In the context of these effects, low or diminishing Se status in some parts of the world, notably in some European countries such as the UK, is giving cause for concern. While deficiency has an adverse effect on immunocompetence, Se supplementation appears to enhance the immune response. Se appears to be a key nutrient in counteracting certain viral infections; thus, in a Se-deficient host the benign coxsackie virus becomes virulent, causing heart damage, the influenza virus causes more serious lung pathology and HIV infection progresses more rapidly to AIDS. Long recognised as essential for successful animal reproduction, Se is required for human sperm maturation and sperm motility and may reduce the risk of miscarriage. Deficiency has been linked to adverse mood states. Findings have been equivocal in linking Se to cardiovascular disease risk, although other conditions involving oxidative stress and inflammation have shown some association with Se status. There is growing evidence that higher Se intakes are associated with reduced cancer risk. While persuasive evidence already exists to suggest that additional Se would be beneficial in some health conditions, results from intervention trials underway or planned have the potential to reinforce or refute the argument for increasing Se intake.

Antioxidants↗