1. Introduction
Selenium (Se) is a trace mineral that plays a critical role in public health. It is a vital component of numerous enzymes and proteins, called selenoproteins, and thus affects a wide range of biological activities, including anti-inflammation, thyroid function, fertility, DNA synthesis, and reproduction ( 3 , 4 ). Selenium is also known for its potent antioxidant function ( 5 , 6 ). A substantial proportion of the population exhibits inadequate intake of Se, attributable to the limited bioavailability of Se in soil and the low concentrations of Se present in vegetables ( 7 ). A prevalent approach to augmenting the Se content of food products involves the enrichment of foods with the organic form of Se. In this regard, live yeast cells have been observed to absorb Se and convert it into L (+) selenomethionine ( 8 ). It is noteworthy that selenomethionine, a derivative of Se, is considered toxic in its inorganic form when consumed in high doses (mg) ( 9 ). Moreover, there is a prevalent report of abnormal levels of serum liver enzymes in hypothyroid patients ( 10 ). The relationship between thyroid and liver health is intricate, with the activation of thyroid hormones being contingent on the liver's role ( 10 ). Reports indicate that maintaining an average level of Se is essential for averting thyroid disorders. Conversely, studies have indicated a heightened risk of developing thyroid cancer in cases of Se deficiency ( 11 , 12 ). A direct relationship has been demonstrated between selenium (Se) levels in serum and low-density lipoprotein (LDL) cholesterol, triglycerides, and total cholesterol concentrations in populations with high Se levels ( 13 , 14 ). In this study, we examined the effects of Se on liver enzymes, lipid factors, hemoglobin (HGB), malondialdehyde (MDA), total antioxidant, and glutathione reductase levels under a double-blinded clinical trial performed on patients with Hashimoto's disease.
2. Materials and Methods
2.1. Study Population
A prospective randomized, double-blind, placebo-controlled clinical trial was conducted on 40 patients with subclinical hypothyroidism symptoms aged 18–60. The study was conducted from July 2019 to October 2019 in the outpatient ward of the Endocrine Clinic at Emam Reza Hospital in Tabriz City. Patients were enrolled in the study after providing written consent and receiving a brief description of the study's importance. Diagnoses were made based on TSH levels in two consecutive tests and were subsequently reviewed by an expert endocrinologist. The patients were stratified into two groups: a control group and an intervention group. Patients who had consumed trace element and antioxidant supplements in the previous six months, suffered from renal failure, proteinuria, acute or chronic liver disease, were pregnant, or had heart problems were excluded from the study.
2.2. Sample Size
The sample size was determined based on the findings of a preliminary study (i.e., TSH changes were calculated as the primary outcome before and after the intervention for five subjects per group). The sample size was calculated to be 20 per group using a standard formula for a randomized controlled trial based on the first type error (α) of 0.05 and 80% power, anticipating an approximate dropout rate of 10% during the study. Consequently, 20 participants were enrolled in each group.
2.3. Trial Procedure
Forty patients were randomly allocated to one of the groups (control and treatment) using a randomized block method, in which both participants and investigators were blinded to allocations. The participants' data, including age, gender, weight, and height, were recorded before the study began. The height and weight of the participants were measured without shoes and with minimal clothing via a calibrated scale and stadiometer.BMI was calculated as weight (kg)/height (m2). The subjects in the treatment group were administered 200 μg of selenium in the form of a capsule containing selenium-enriched yeast once daily for eight weeks. The control group received a placebo capsule. Selenium-enriched yeast was produced at the Nutrition Research Center, Tabriz University of Medical Sciences, Iran, through the cultivation of Saccharomyces cerevisiae in selenium-rich media ( 15 , 16 ). During the study, the participants maintained their usual physical activity, dietary, and medication intake. The effects of Se consumption were monitored weakly in participants.
2.4. Metabolic Parameters
Venous blood samples were obtained from each participant before and after Se supplementation consumption. The following parameters were measured: TSH (normal range: 5.0 milli-international units per liter (mIU/L)), anti-TPO (normal range: less than 34 international units per millimeter (IU/ml)), total blood catalase, malondialdehyde (MDA), serum cholesterol level, liver enzymes (ALT and AST), glutathione reductase (GR), and total antioxidant capacity (TAC) were measured by commercial methods. The spectrophotometric method was used to measure the blood MDA, TCA, HGB, and GR. The serum total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), ALT, and AST were measured via an auto analyzer.
2.5. Statistical Analysis
A comprehensive set of descriptive parameters was obtained for all the study variables in each group. The Kolmogorov-Smirnov test was then employed to assess the normality of these variables.
3. Results
The present study randomly classified patients into two groups: the intervention group (mean age: 39.36 ±2.41) and the control group (mean age: 45.38 ±3.29). The levels of TSH and Anti-TPO were examined in both groups. The results indicated a relative decrease in TSH and Anti-TPO levels; however, no significant difference existed between the intervention and placebo groups at the baseline and after treatment. Furthermore, the mean levels of GR, TAC, ALT, AST, total cholesterol, HDL-C, LDL-C, VLDL, TG, MDA, and HGB were evaluated in both groups at the baseline and following treatment, as illustrated in Table 1. The findings of the study demonstrated that the catalase level experienced an increase in the intervention group during the 60-day treatment period with Se capsules. Additionally, the HDL, LDL, TG, total cholesterol, and VLDL values exhibited a significant reduction during the treatment phase with Se capsules. The within-group comparison revealed a statistically significant reduction in the mean MDA level (P = 0.004) and a substantial increase in the mean HGB level (P=0.038) in the intervention group following treatment with the Se supplement. In contrast, the placebo group exhibited no statistically significant variation in MDA (P=0.794) or HGB (P=0.798) levels. The findings revealed that none of the metabolic factors were influenced by demographic factors, except for HDL and HGB levels, which exhibited a significant dependency on gender (P=0.074) and BMI (P=0.019), respectively (Table 2).
Variables | Before Se Treatment | After Se Treatment | Before Placebo Treatment | After Placebo Treatment | P. value in treatment group | p.value in placebo group |
---|---|---|---|---|---|---|
GR | 13.1±0.1 | 13.19±0.15 | 13.05±0.09 | 13.04±0.08 | 0.752 | 0.912 |
TAC | 1.52±0.03 | 1.64±0.02 | 1.59±0.02 | 1.67±0.07 | 0.06 | 0.273 |
ALT | 35.36±0.64 | 33.93± 0.67 | 35.54±0.31 | 35.78±0.42 | 0.804 | 0.533 |
AST | 34.6±1.13 | 33.07±0.82 | 34.31±0.48 | 34.14±0.58 | 0.816 | 0.823 |
CAT | 69.64±11.82 | 122.91±11.95 | 92.15±6.57 | 83.07±10.88 | 0.62 | 0.462 |
HGB | 13.64±0.37 | 13.82±0.2 | 13.57±0.33 | 13.46±0.26 | 0.038 | 0.798 |
MDA | 1.97±0.18 | 1.09±0.01 | 1.75±0.08 | 1.1±0.01 | 0.049 | 0.794 |
Total Cholesterol | 190.8±9.1 | 180.6±12.67 | 197.8±8.08 | 210.5±14.3 | 0.347 | 0.468 |
HDL-C | 23.83±2.19 | 21.56±1.89 | 28.17±1.68 | 25.97±1.82 | 0.544 | 0.339 |
LDL-C | 128.95±5.1 | 123.34±5.38 | 140.02±8.79 | 152.32±13.8 | 0.916 | 0.462 |
V-LDL | 31.38±4.88 | 28.2±4.33 | 28.84±4.68 | 32±4.24 | 0.229 | 0.623 |
TG | 156.9±24.41 | 141.4±21.94 | 144.2±23.41 | 160±21.2 | 0.952 | 0.633 |
TSH | 8.31±4.2 | 7.7±2.32 | 8.09±0.93 | 6.56±1.18 | 0.467 | 0.269 |
Anti-TPO | 457.06±139.26 | 396.82±142.16 | 483.49±144.06 | 521.79±128.84 | 0.399 | 0.395 |
Variables | Gender | Age | Waist | Height | Weight | BMI |
---|---|---|---|---|---|---|
HDL-C | 0.074 | 0.919 | 0.756 | 0.254 | 0.426 | 0.351 |
VLDL | 0.134 | 0.526 | 0.958 | 0.338 | 0.474 | 0.46 |
LDL-C | 0.9 | 0.927 | 0.647 | 0.351 | 0.322 | 0.328 |
TG | 0.134 | 0.526 | 0.958 | 0.338 | 0.474 | 0.46 |
Total Cholesterol | 0.443 | 0.435 | 0.567 | 0.384 | 0.268 | 0.269 |
MDA | 0.109 | 0.843 | 0.676 | 0.238 | 0.439 | 0.371 |
HGB(g/dL) | 0.233 | 0.777 | 0.373 | 0.011 | 0.021 | 0.019 |
Catalase | 0.887 | 0.968 | 0.556 | 0.664 | 0.702 | 0.692 |
GR | 0.826 | 0.451 | 0.252 | 0.324 | 0.3 | 0.315 |
TAC | 0.183 | 0.13 | 0.354 | 0.684 | 0.815 | 0.809 |
ALT | 0.566 | 0.838 | 0.621 | 0.295 | 0.328 | 0.286 |
AST | 0.887 | 0.474 | 0.157 | 0.417 | 0.517 | 0.504 |
4. Discussion
In light of the escalating prevalence of thyroid disease and the deleterious side effects of thyroid disorders on public health, the introduction of effective control and prevention strategies is imperative. For instance, there is a direct relationship between thyroid diseases and liver disorders ( 18 ). This study examined the effect of selenium, a confirmed dietary supplement, on thyroid hormones, liver enzymes, and lipid factors. The findings of the study indicated a decline in lipid factors (TGD, VLDL, LDL, HDL, and total cholesterol) in the selenium group, though the differences observed between the two groups were not statistically significant. The study concluded that selenium exerts no significant influence on plasma lipid profiles; however, it did modify lipid factor values in comparison with the placebo group. These observations are consistent with a recent meta-analysis study that reported a marginal effect on reducing TG levels and an absence of effect on total cholesterol and HDL-C levels ( 19 ). However, the reduction of MDA level was found to be significantly dependent on selenium (P<0.05), as indicated by the GR, CAT, and TAC enzymes, which demonstrated a slight increase compared with the placebo group ( 20 , 21 ).In this study, liver enzymes, including ALT and AST, were also evaluated, indicating a relative reduction compared to the placebo group, consistent with findings from similar studies ( 22 , 23 ). The study also noted a relative decrease in TSH and anti-TPO values, though this difference was not statistically significant between the two groups. These results align with previous studies that have observed the weak effect of selenium in patients with autoimmune hypothyroidism ( 24 ) and its lack of effect on TPO Ab levels in women with autoimmune hypothyroidism ( 25 ). The present study found that Selenium consumption in Hashimoto's thyroiditis was associated with improved serum lipid factors, liver enzymes, anti-thyroid peroxidase antibody, MDA, and HGB levels. The findings underscore the significant effect of selenium supplementation on serum MDA and HGB levels in subclinical hypothyroidism patients. However, given the conflicting results related to the impact of selenium supplements on serum lipid factors and liver enzymes, further research with larger sample sizes and varying doses of selenium is recommended to achieve more precise conclusions.
Acknowledgment
This study was supported by the Nutrition Research Center at Tabriz University of Medical Sciences, Tabriz, Iran.
Authors' Contribution
A.H. and A.D. designed the study and performed the data analysis and interpretation; A.F. and M.M. revised the manuscript. A.O. wrote the first draft. B.K. discussed the results. The authors read and approved the final manuscript.
Ethics
The study was conducted subsequent to ethical approval by the ethics committee of Tabriz University of Medical Sciences, Tabriz, Iran (reference number: IR. TBZMED. REC.1398.339). The study was also registered on the website of the Iranian Registry of Clinical Trials (IRCT20190212042686N2), which is available at the following address: https://www.irct.ir/.
Conflict of Interest
The authors have no conflict of interest.
Data Availability
The datasets utilized and/or examined during the present study are available upon reasonable request to the corresponding author.
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