Selenium in Human Organism. Report

Definition of the Clinical Problem

Selenium (Se) is an essential trace mineral that participates greatly in the reduction of the damage done by electron-seeking free-radicals in human cell membranes. This is why low selenium status is generally linked to morbidity and mortality due to infectious as well as chronic diseases and cancer. According to Combs (2001), the deprivation of selenium can be linked with the impairments in antioxidant protection, redox regulation and energy production as consequences of suboptimal expression of one or more of the Se-containing enzymes. These impairments may not cause deficiency signs in the classical sense, but instead contribute to health problems caused by physiological and environmental oxidative stresses and infections.

When dealing with immune-compromised patients (i.e. those with HIV/AIDS, diabetes, or those undergoing chemotherapy), current research had found great potential in the micronutrient selenium because intakes greater than those required for selenocysteine enzyme expression have been found to reduce cancer risk and increase human immune functions. Specifically, Ryan-Harshman and Aldoori (2005) reported that this element can trigger immune function in the human body because they say that “selenium deficiency can impair both cell-mediated immunity and B cell function” (p. 98). Broome et al. (2004) also suggested that “overt selenium deficiency is associated with dilated cardiomyopathy, skeletal muscle myopathy, osteoathropathy, and cretinism (in iodine-deficient populations), and more marginal deficiencies may contribute to reduced immune function, some cancers, and viral diseases”. Upon reading these groundbreaking studies as a basis for investigation, our research considered what has been noted about the use of selenium for improving outcomes for patients with compromised immune systems.

Summary of the Findings

In Broome et al. (2004), their study sought to assess “whether administration of small selenium supplements to otherwise healthy UK subjects leads to functional changes in immune status and the rates of clearance and mutation of a picornavirus: live attenuated polio vaccine”. In order to achieve their objective, they conducted a research using “twenty-two adult UK subjects with relatively low plasma selenium concentrations (<1.2 µmol/L, ≈60% of those screened)”. They administered “50 or 100µg Se (as sodium selenite) or placebo daily for 15 wk in a double-blind study” among these patients and all of the subjects received “an oral live attenuated poliomyelitis vaccine after 6 wk and enriched stable ⁷⁴Se intravenously 3 wk later”. After the tests, the researchers found that “selenium supplementation increased plasma selenium concentrations, the body exchangeable selenium pool (measured by using ⁷⁴Se), and lymphocyte phospholipid and cytosolic glutathione peroxidase activities”. Thus, the selenium supplements had a positive effect on “the cellular immune response through an increased production of interferon ϒ and other cytokines, an earlier peak T cell proliferation, and an increase in T helper cells”, although “humoral immune responses were unaffected”. Also, Broome et al. (2004) indicated that “selenium-supplemented subjects also showed more rapid clearance of the poliovirus, and the poliovirus reverse transcriptase–polymerase chain reaction products recovered from the feces of the supplemented subjects contained a lower number of mutations”. Ultimately, the researchers concluded that the data they gained using their subjects who received placebo revealed that they had “a functional selenium deficit with suboptimal immune status and a deficit in viral handling”. Also, the researchers insisted “that the additional 100 µg Se/d may be insufficient to support optimal function”.

On the other hand, Hurwitz et al. (2007) studied supplementing selenium to improve immune functioning of people infected with human immunodeficiency virus (HIV). In this study, the researchers administered “high selenium yeast supplementation (200 μg/d)” to 450 subjects who participated in the screening assessment. The results were evaluated using a “double-blind, randomized, placebo-controlled trial” and the intention-to-treat analyses were assessed based on the effect of “HIV-1 viral load and CD4 count after 9 months of treatment”. Of the 450 initial subjects, “262 initiated treatment and 174 completed the 9-month follow-up assessment”. Their data revealed a “mean adherence to study treatment” of (73.0%±24.7%), which was considered “good… with no related adverse events”. Also, the “intention-to-treat analyses indicated that the mean change (Δ) in serum selenium concentration increased significantly in the selenium-treated group and not the placebo-treated group”, while “greater levels predicted decreased HIV-1 viral load (P<.02), which predicted increased CD4 count (P<.04). The researchers also revealed that their results “remained significant after covarying age, sex, ethnicity, income, education, current and past cocaine and other drug use, HIV symptom classification, antiretroviral medication regimen and adherence, time since HIV diagnosis, and hepatitis C virus coinfection”. In their follow-up analyses, the treatment effectiveness was even bolstered by the fact that “nonresponding selenium-treated subjects whose serum selenium change was less than or equal to 26.1 μg/L displayed poor treatment adherence”, while selenium-treated subjects had visible increase in serum selenium increase that was greater than 26.1 μg/L that “evidenced excellent treatment adherence”, “no change in HIV-1viral load” and these subjects had “an increase in CD4 count”.

Lastly, Stranges et al. (2004) conducted a study to determine “the effect of long-term selenium supplementation on the incidence of type 2 diabetes”. This was done after some successful findings in research that used animal subjects had revealed the fact that “selenium supplementation improves glucose metabolism”. By conducting a research that involved 1202 patients “who were recruited in 1983 to 1991 from 7 dermatology clinics in areas of low selenium consumption of the eastern United States” and “who who did not have type 2 diabetes at baseline”, the researchers used an NPC (Nutritional Prevention of Cancer) trial, which was “a randomized, double-blind clinical trial designed primarily to evaluate the efficacy of selenium supplementation for prevention of cancer”. By administering 200 µg of selenium daily that was “supplied in a 0.5-g, high-selenium baker’s yeast tablet”, each of their subjects were designated in “unique sequential treatment number” and they were grouped centrally per clinic “using sealed identical pill bottles that were distributed” in their respective clinics. The results of their study revealed, “after an average follow-up of 7.7 years”, the subjects developed type 2 diabetes significantly higher in patients who received selenium supplements (58 selenium recipients and 39 placebo). Moreover, their study had attained results that indicate the “lack of benefit of selenium supplementation” on patients with type 2 diabetes and that their findings “persisted” despite the “analyses stratified by age, sex, body mass index, and smoking status”. Thus, the researchers arrived at a conclusion that “selenium supplementation does not seem to prevent type 2 diabetes” but “it may increase risk for the disease”.

Synthesis of the Results

In the studies of Broome et al. (2004) and Hurwitz et al. (2007), their research provided valuable proof about the efficacy of selenium supplementation in averting viral diseases like polio and AIDS. Their research bolsters the fact of what Combs (2001) explained that selenium was found to be an essential component of the enzyme glutathione peroxidase (GPX) since the 1970s. The enzyme glutathione peroxidase was known to participate in the antioxidant protection of cells by reducing hydroperoxides and this finding was taken to explain the nutritional ‘sparing’ by Se of vitamin E, a known lipid-soluble antioxidant. Although Broome et al. (2004) and Hurwitz et al. (2007) provided ample preliminary data which warrants the development of further research to demonstrate the positive effect of selenium supplementation in specific populations of immunocompromised patients, their research still needs to be replicated in different settings and completed in a scale large enough to make clinical recommendations to recommend the benefits of the treatments they administered.

Compared to the findings of Broome et al. (2004) and Hurwitz et al. (2007) that hailed the positive effects of selenium supplementation, Stranges et al. (2004) research might be the devil’s advocate that might bolster the idea of being careful in administering selenium supplementation. This is because their study found that instead of decreasing the risk of type 2 diabetes, Stranges et al. (2004) had gathered enough data to prove that selenium might increase the propensity of the patient to develop type 2 diabetes. Although there might be loopholes that can be identified in their study like “diabetes was a secondary outcome in the parent trial” because the study was intended for cancer research and the “diagnoses of diabetes were self-reported”, their findings need to be verified further to reveal the unknown side effects of selenium supplementation. In this case, we recommend more research in the area of long-term selenium supplementation to determine the real impact of this treatment. Through this, physicians and nurses will be informed of how much selenium supplementation will be considered safe to use in the future without the unwanted ill effects on their overall health.

Comparative Evaluation Phase

Fit of Setting

To comparatively evaluate the studies selected for this investigation, Table 1 presents an overview of whether or not the solutions found in each of the research studies can be used in the selected clinical setting—i.e. providing service to patients with compromised immune systems. Moreover, the table summarizes the setting of the research and provides some review of whether or not the specific research study lends itself for use in the selected population.

Table 1: Fit of Setting Comparison

Substantiating the Evaluation

The research of Broome et al. (2004) and Hurwitz et al. (2007) had substantial results that indicate the effectiveness of selenium supplementation and its positive effect on the human immune response. Although actual clinical studies that evaluate the effectiveness of selenium for boosting immune system function have not been performed, both studies indicate that similar results in research will demonstrate the potential link between selenium and immune system response. For example, Broome et al. (2004) found out that “selenium-supplemented subjects… showed more rapid clearance of the poliovirus, and the poliovirus reverse transcriptase–polymerase chain reaction products recovered from the feces of the supplemented subjects contained a lower number of mutations”. This finding indicate that the data they gathered is “potentially relevant to emerging viral diseases, where the selenium nutrition of the host may play a role in viral evolution”.

On the contrary, Stranges et al. (2004) had gathered enough data to prove that selenium might increase the propensity of the patient to develop type 2 diabetes. The findings of their research entirely affect the two previous studies in the sense that patients might be afflicted with type 2 diabetes if they are exposed to selenium supplementation in the long-term basis. Although there are several loopholes in this study, its contribution to the knowledge about the link of selenium and human immune response is great because it provides the another picture of how selenium can be detrimental with long –term use. It is suggested that this area of research needs to be pursued in order to bolster or debunk the claims of this particular research. It will also forewarn medical practitioners to be careful in administering selenium in patients in order to avoid the unwanted consequences.

Basis for Practice

The above-mentioned studies essentially contributed in the current literature the important link of selenium intake and outcomes for the immune system. Although everything was not hailing that selenium has all benefits and no side effects, these studies can be instruments to springboard more research on selenium supplementation and provide different settings in order to support or debunk the claims made by these authors. Since the 1970s, Combs (2001) explained that selenium was found to be an essential component of the enzyme glutathione peroxidase (GPX). Since that enzyme was known to participate in the antioxidant protection of cells by reducing hydroperoxides, this finding was taken to explain the nutritional ‘sparing’ by Se of vitamin E, a known lipid-soluble antioxidant. At present, several Se-containing enzymes are recognized: at least five GPX isoforms, three iodothyronine 59-deiodinases, three thioredoxin reductases, selenophosphate synthetase (Allan et al., 1999). In addition, at least four other proteins are recognized as specifically incorporating Se, although their metabolic functions remain unclear: plasma selenoprotein P, muscle selenoprotein W and selenoproteins in prostate and placenta. In each of these proteins, selenium is incorporated into the amino acid selenocysteine (SeCys) by the co-translational modification of tRNA-bound serinyl residues at certain loci encoded by UGA codons containing SeCys-insertion sequences in their 39-untranslated regions. This enables the decoding of UGA as SeCys rather than as a stop signal, which is its usual function. Thus, the nutritional essentiality of selenium appears to be due to the functions of SeCys proteins: antioxidant protection by the GPX, energy metabolism affected by the iodothyronine 59-deiodinases, and redox regulation of transcriptional factors and gene expression by the thioredoxin reductases.

Despite the proven importance of selenium, Combs (2001) lamented that food systems of most populations do not currently provide enough selenium to support the maximal expression of the SeCys-enzymes. It can, thus, be assumed that many individuals have compromised protection from oxidative stress, which increases their risks to various chronic diseases, including those of the heart and lungs, as well as cancer. By helping to dismantle the free-radical compounds, selenium works toward the same goal as vitamin E in providing antioxidant protection to the body. A selenium deficiency results in muscle and heart disorders. In this case, although insufficient evidence of adverse health consequences from current selenium intakes to warrant action, fortification programs should still be advocated so that average daily requirements for selenium will be maintained. Also, a link of its triggering type 2 diabetes should be explored so that the findings of Stranges et al. (2004) will be verified further.

Feasibility

The benefits of using the effectiveness of selenium in supporting immune response in the clinical setting appear to be quite numerous. In addition to the fact that increased selenium intake may improve health outcomes for the patient, there is evidence which suggests that this practice may also improve the quality of life for the patient. In addition, increasing selenium intake does not require extensive changes for the patient. Rather, patients could be provided with a supplement that could be taken each day. The actions required by patients are minimal and non-invasive. Thus, doubling patient intake of selenium is a relatively simple process which could improve the ability of clinicians to create efficacy in treatment outcomes.

Even though the proposed intervention is simple to implement, the National Institutes of Health (2008, Dietary…) reports that excess selenium levels—greater than 400µg/dL can result in selenosis. While these types of overdoses are rare, they may occur in patients that do not closely monitor their selenium supplement intake. In addition, the decision to implement this change in clinical practice will require additional testing to ensure the safety of the patient. Finally, the use of selenium supplements for patients with compromised immune system will require behavior change on the part of the patient. Given all of the demands of treating a compromised immune system, there is concern that adding another treatment may be difficult for the patient.

Decision-Making Phase

Pilot Study

The pilot study that would be used for this clinical trial would be a randomized control trial in which immunocompromised patients—i.e. those with cancer or HIV—would be randomly assigned to one of two groups: control group in which no effort is made to increase selenium intake and an experimental group in which selenium intake would be doubled. The trial would take place over the course of a three month period. Baseline measures for immune system function, health of the patient and overall quality of life would be made. These measures would again be applied at the half-way point and again at the completion of the 12 week trial period. The data collected would be aimed at understanding whether or not an increase in selenium intake impacted specific domains of the patient’s overall health. Patients enrolled in the program would have to be relatively stable in their diagnosis and demonstrate positive healthcare behaviors—i.e. actively seek treatment for their condition.

Persons or Groups that Would Implement Change

In order to carry out this pilot study, individuals receiving treatment for HIV or cancer would be required to increase their selenium uptake through the use of selenium supplements. Subjects that would be considered for this initial investigation would be patients are actively seeking treatment for their conditions and those that are relatively stable with regard to their treatment—i.e. patients with HIV that have not progress to full-blow AIDS or that do not have active infections or cancers. This target population would need to take selenium supplements in order to determine the impact of this treatment on improving health outcomes and quality of life.

While patients will be the primary group impacted by this change, clinicians working with patients will also need to make changes to incorporate this therapy into practice. For example, nurses working with immunocompromised patients will need to provide education and support to help patients understand the importance of selenium therapy. In addition physicians will need to understand the utility and importance of this therapy in providing service to patients. All healthcare professionals may be called upon to answer questions or provide information. Thus, this change will require extensive healthcare support in order to be effective.

Motivations for Change

With regard to motivations for change in this population, it seems reasonable to argue that patients with compromised immune systems have a number of different motivators for change. First, individuals in this population often deal with chronic health issues such as pain related to their conditions or treatment. If selenium can improve day-to-day outcomes for the patient, the motivation for change would be improved quality of life. Second, individuals with compromised immune systems face ongoing health challenges which may impact their mortality. If patients are made aware of the potential improvements that can be garnered through treatment, they may be motivated by the promise of improved health over the long-term.

Generally speaking, improved quality of life and improved health outcomes represent two viable motivators for promoting change among immunocompromised patients. Given that selenium therapy may have benefits in both of these areas, there is some evidence which suggests that this intervention could motivate patients in this clinical group to engage in the intervention. Education regarding these specific areas would be imperative to help bolster motivation and encourage patients to continue to utilize the intervention.

Barriers to Change

Even though there are clear motivators which may impact the decision of the patient to engage in change, the reality is that there are notable barriers which may also impact outcomes in this group. Individuals with compromised immune systems face physical and mental health challenges related to their conditions. Patients that are suffering from depression or anxiety may not be able to be proactive about their health behaviors. This can impact the outcomes of intervention, creating notable gaps among patients that agree to engage in this therapy. Further, immunocompromised patients such as those with HIV often consume large quantities of drugs in order to maintain their health. The need for additional drug therapy may result in resistance on the part of the patient to engage in therapy.

Two Methods to Overcome Barriers to Change

Considering what can be done to overcome these barriers noted above, it seems reasonable to argue that healthcare providers must comprehensively evaluate their patients in order to identify mental health issues which may interfere with treatment. This data can then be used to develop specific care which will improve care provided to the patient and encourage the patient to engage in the intervention. The second method that can be used to reduce the barriers noted above is education. Patients that are provided with clear information regarding the importance of the intervention may be willing to engage in the treatment. Further, by discussing these issues with the patient, the clinician may be able to provide some practical advice on when to take the supplement such that it does not require too much additional effort on the part of the patient.

Communication of Findings

• Administration of the Organization: In order to communicate the findings of the project to the administration of the organization, a formal report detailing the specifics of the project, the methodology employed and the outcomes achieved should be provided. This will elucidate the comprehensiveness and thoroughness of the project and its importance for expansion.
• Staff Nurses: Communication to staff nurses should be provided in the form of a truncated report which delineates the clinical guidelines that should be followed in providing service to patients.
• Ancillary Staff: Communication to ancillary healthcare staff including physicians should also involve a truncated report with a clear summary which demonstrates: the importance of the intervention, the need for the intervention and the clinical guidelines that will be most effective for improving patient outcomes.
• Public: Communication to the public regarding the outcomes of the project must include written and visual support to demonstrate the benefits of selenium. An educational pamphlet may be the most appropriate format to convey information in a manner that is both informative and feasible for meeting the needs of reader that may not be well educated on the subject.

References

Allan C.B., Lacourciere G.M. and Stadtman, T.C.(1999). Responsiveness of selenoproteins to dietary selenium, Annual Reviews of Nutrition, 19, 1-16.

American Psychological Association. (2001). Publication manual of the American Psychological Association (5^th ed.). Washington, DC: Author.

APA Style. (2006). Web.

Broome C.S., McArdle, F., Kyle, J.A., Andrews, F., Lowe, N.M., Hart, C.A., Arther, J.R., & Jackson, M.J. (2004). An increase in selenium intake improves immune function and poliovirus handling in adults with marginal selenium status, American Journal of Clinical Nutrition, 80: 154-62.

Combs, G.F. (2001, May). Selenium in global food systems, British Journal of Nutrition, 85(5): 17-547.

Hurwitz, B.E., Klaus, J.R., Llabre, M.M., Gonzalez, A., Lawrence, P.J., Maher, K.J., Greeson, J.M., Baum, M.K., Shor-Posner, G., & Skyler, J.S. (2007, Jan. 22). Suppression of human immunodeficiency virus type 1 viral load with selenium supplementation: a randomized controlled trial, Archives of Internal Medicine, 167(2):148-54.

National Institutes of Health. (2008). Dietary supplement fact sheet: Selenium. Web.

Stranges, S., Marshall, J.R., Natarajan, R., Donahue, R.P., Trevisan,M., Combs, G.F., Cappuccio,F.P., Ceriello, A., & Reid, M.E. (2007). Effects of long-term selenium supplementation on the incidence of type 2 diabetes: A randomized trial, Annals of Internal Medicine, 147(4):217-224.

Van den Brink, M.R., Alpdogan, O., & Boyd, R.L. (2004). Strategies to enhance T-cell reconstitution in immunocompromised patients. Nature Reviews Immunology, 4(11): 856-867.

Kelly, G. A. (1963). A theory of personality: The psychology of personal constructs. New York: Norton.

Format APA headings for your paper. (2004). The Writing Center, University of Madison-Wisconsin. Web.