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Do Dietary Supplements Affect Inflammation, Oxidative Stress, and Antioxidant Status in Adults with Hypothyroidism or Hashimoto's Disease?-A Systematic Review of Controlled Trials.
Kubiak, K, Szmidt, MK, Kaluza, J, Zylka, A, Sicinska, E
Antioxidants (Basel, Switzerland). 2023;12(10)
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A deficiency of the thyroid hormone causes hypothyroidism (HT), whereas Autoimmune thyroiditis (AIT) is mainly an organ-specific autoimmune condition. Both HT and AIT are characterised by low-grade inflammation and inflammation in the thyroid gland. Dietary supplements may offer health benefits; however, previous research findings are inconclusive. This systematic review evaluated twenty-two controlled studies to understand the effectiveness of dietary supplements in reducing inflammation and oxidative stress and improving antioxidant and thyroid parameters in patients with HT or AIT. The efficacy of dietary supplements in improving thyroid health and reducing inflammation and oxidative stress was inconclusive due to the low quality of the included studies and the limited number of available studies. Selenium supplements might be beneficial in improving thyroid parameters and inflammation in patients with HT or AIT. Even though the therapeutic benefits of dietary supplements in treating thyroid disease were inconclusive, healthcare professionals can use them to address the common nutritional deficiencies in people with HT and AIT. Further, large, long-term, robust studies are required to assess the therapeutic utility of different dietary supplements in promoting the health of the thyroid gland.
Abstract
This systematic review aims to summarise the results of controlled trials on dietary supplements (DS) usage and inflammation, oxidative stress, antioxidant status, and thyroid parameter improvement in hypothyroidism (HT)/Hashimoto's thyroiditis (AIT) patients. The study protocol was registered with PROSPERO (no. CRD42022365149). A comprehensive search of the PubMed, Scopus, and Web of Science databases resulted in the identification of nineteen randomised controlled trials and three non-randomised studies for the review; three studies examined the effect of supplementation with vitamin D, twelve studies-with selenium, and seven studies-with other DS. Based on very limited evidence, the lack of influence of vitamin D supplementation on inflammatory parameters was found, while no studies have examined oxidative stress and antioxidant status parameters, and only one provided results for a single thyroid parameter after an intervention. Some evidence was found proving that selenium supplementation may decrease inflammation and improve thyroid parameters, but reaching a conclusion about its influence on oxidative stress and antioxidant status is not possible because of the insufficient number of studies. Additionally, due to examining other DS (e.g., multicomponent, Nigella sativa, and genistein) only in single studies, conclusions cannot be drawn. Further long-term, high-quality randomised controlled trials are necessary to better understand the influence of DS on inflammation, oxidative stress, and antioxidant status, as well as their potential to improve thyroid gland function in HT/AIT patients.
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Effect of selenium on thyroid autoimmunity and regulatory T cells in patients with Hashimoto's thyroiditis: A prospective randomized-controlled trial.
Hu, Y, Feng, W, Chen, H, Shi, H, Jiang, L, Zheng, X, Liu, X, Zhang, W, Ge, Y, Liu, Y, et al
Clinical and translational science. 2021;14(4):1390-1402
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Hashimoto thyroiditis (HT) is the most common thyroid autoimmune disease. Multiple factors contribute to the development of the disease leading to immune system-mediated destruction of the thyroid gland. In the absence of specific therapeutic approaches that address the immunological activity, thyroid hormone replacement is the primary treatment. Selenium (Se) is an essential trace element for humans and the thyroid gland utilises high amounts of selenium for the production of enzymes and antioxidants. Supplementing Se has shown positive effects in HT, as demonstrated in some studies. Yet, there have been inconsistencies in the results and the understanding of the mechanisms involved are limited. The authors of this prospective, randomized controlled study tried to shed some light on the efficacy of Se supplementation and its mechanisms. 43 HT-patients on no thyroid medication, received 200mcg Se per day for 6 months. Various markers were assessed including antibodies, thyroid stimulating hormone (TSH), antioxidant enzymes and T-helper immune cells that regulate immunological activity, which were compared to the HT-control group (n=47) and healthy individuals (n=36). The outcome of the intervention showed that Se supplementation can reduce thyroid antibodies, and TSH and can increase antioxidant enzymes in patients with HT and along with the findings the authors discussed some potential mechanisms at play. This study suggests that supplementary Se can benefit HT, particularly subclinical HT.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Selenium supplementation is reported to reduce TPOAb, TGAb, and TSH levels, as well as increase Se, GPx3, and SePP1 concentrations in patients with HT without the use of levothyroxine replacement.
- Practitioners could consider selenium supplementation in patients with HT who have serum selenium levels less than 120ug/L.
Evidence Category:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
A prospective randomised controlled trial was conducted to investigate the effect of selenium (Se) supplementation in patients with Hashimoto’s thyroiditis (HT). The study also explored the potential mechanisms of action of Selenium in thyroid autoimmunity.
One hundred and twenty-six subjects (90 with HT and 36 healthy individuals) were included in the study. The patients with HT were randomly assigned into two groups. The Se-treated group (n=43) received 200ug of selenium in a selenious yeast tablet (SYT) per day for 6 months. No treatment was given to the control group (n=47). At the endpoint, 126/126 subjects completed the study.
Primary clinical outcomes were:
- Antithyroid peroxidase antibodies (TPOAb) levels were significantly lower compared with the control group at 6 months (ΔTPOAb [IU/ml] = −28.4 [−103.9,0] vs. 0 [−18.1, 20.5], p = 0.001).
- There was a significant difference in antithyroglobulin antibodies TGAb titers between the Se-treated group and the control group at 6 months (ΔTGAb [IU/ml] = −48.8 [−139.7, −2.0] vs. 18.3 [−23.5, 77.4], p = 0.001.
- Compared with baseline, thyroid stimulating hormone (TSH) presented slightly lower levels in the Se-treated group, whereas there was a statistical increase in the control group at 6 months (ΔTSH [mIU/L] = −0.16 [−2.1, 0.28] vs. 0.48 [−0.15, 1.47], p = 0.001).
Secondary clinical outcomes were:
- aTreg cells in the Se-treated group were significantly higher than the control group at 6 months (13.19 ± 3.5 vs. 11.49 ± 2.79, p = 0.012)
- There was a pronounced increase in glutathione peroxidase (GPx3) at 6 months of treatment in the Se-treated group compared with the control group (p=0.028).
- Furthermore, Selenoprotein P1 (SePP1) levels increased in the Se-treated group compared with the control group at 6 months (17.2 [9.8, 22.1] vs. 10.7 [8.9, 14.6], p = 0.007).
Clinical practice applications:
- There is no specific approach to suppress autoimmunity, thus thyroxine replacement has become the generally accepted therapy for patients with Hashimoto’s thyroiditis (HT) with hypothyroidism.
- The thyroid gland contains the highest concentration of selenium, which is incorporated into selenoproteins, such as glutathione peroxidase (GPx), selenoprotein P (SePP), thioredoxin reductase, and iodothyronine deiodinases. These selenoenzymes play important roles in thyroid hormone metabolism by acting as antioxidants and immunomodulators.
- Based on this study, practitioners could therefore consider using 200ug of selenium for six months as a supportive measure specifically in patients with serum selenium levels less than 120ug/L.
Considerations for future research:
- Although about 20 studies have investigated the treatment of selenium in HT further research is warranted to help explore the appropriate use of selenium.
- Furthermore, investigations are needed to establish if certain HT patients could benefit more from Se supplementation.
- Additionally, investigations are needed to understand the relationship between selenium and Treg cells and their impact on thyroid antibodies.
- This study was completed over six months, longer studies are required to investigate the effect of selenium supplementation over the clinical course of HT.
Abstract
Selenium (Se) is an essential trace element in human. Recent studies of Se supplementation on the effect of Hashimoto's thyroiditis (HT) have been reported, but the exact benefit is unclear as well as the underlying immunologic mechanism. We aimed to evaluate the clinical effect of Se supplement in patients with HT, and explore the potential mechanism against thyroid autoimmunity. A prospective, randomized-controlled study was performed in patients with HT assigned to two groups. Se-treated group (n = 43) received selenious yeast tablet (SYT) for 6 months, whereas no treatment in control group (n = 47). The primary outcome is the change of thyroid peroxidase antibody (TPOAb) or thyroglobulin antibody (TGAb). Second, thyroid function, urinary iodine, Se, Glutathione peroxidase3 (GPx3), and Selenoprotein P1 (SePP1) levels were measured during the SYT treatment. Meanwhile, regulatory T cells (Tregs) and their subsets activated Tregs (aTregs), resting Tregs, and secreting Tregs, as well as Helios and PD-1 expression on these cells were also detected. The results showed that SYT treatment significantly decreased TPOAb, TGAb, and thyroid stimulating hormone (TSH) levels, accompanied with the increased Se, GPx3, and SePP1, compared with the control group. Subgroup analysis revealed that subclinical HT may benefit more from this treatment in the decrease of TSH levels by interaction test. Moreover, the percentage of aTregs, Helios/Tregs, and Helios/aTregs were significantly higher in the Se-treated group than control. In conclusion, Se supplementation may have a beneficial effect on thyroid autoantibodies and thyroid function by increasing the antioxidant activity and upregulating the activated Treg cells.
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The correlation between selenium levels and autoimmune thyroid disease: a systematic review and meta-analysis.
Zuo, Y, Li, Y, Gu, X, Lei, Z
Annals of palliative medicine. 2021;10(4):4398-4408
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Autoimmune thyroid disease (AITD) encompasses several autoimmune conditions affecting the thyroid gland. Genetics, environmental and lifestyle factors influence the condition. Part of the clinical presentation is an abnormal function of the thyroid and the presence of antibodies against thyroid proteins, such as antithyroglobulin antibody (TGAb) and anti-thyroid peroxidase antibody (TPOAb). Selenium is a trace mineral essential to the human body and an important building block for a particular family of proteins called Selenoproteins. This protein family exerts enzymatic functions and plays a major role in thyroid health, furthermore, also in hormone synthesis and managing oxidative stress. Previous research noted that supplemental selenium had beneficial effects on thyroid hormones and antibodies. This systematic review and meta-analysis sought to collectively examine the effect of selenium supplementation on hormone and antibody levels in people with AITD. Blood values investigated were TSH (thyroid stimulating hormone), FT3 (free triiodothyronine), FT4 (Thyroxine), TPOAb, and TGAb. The review included 17 randomised controlled trials, with a total of 1,095 subjects with AITD, plus controls. The cumulated results demonstrated that selenium can notably decrease blood levels of FT3, FT4, and TPOAb in patients with AITD. However, levels of TSH and TGAb seemed not to be significantly affected by selenium supplementation. The authors highlighted that the review was not specific to a particular AITD and that there was limited literature available concerning TGAb levels. More research is needed to clarify the benefits of selenium in AITD.
Abstract
BACKGROUND This investigation systematically evaluated the selenium levels and the effects of selenium supplementation in patients with autoimmune thyroid disease (AITD). METHODS Randomized controlled trials (RCTs) related to selenium supplementation in patients with AITD were selected from the PubMed, Medline, Web of Sciences, Embase, Cochrane Library, and Spring databases. All related literature published between January 2000 and November 2020 were included. The RCT bias risk assessment was conducted according to the Cochrane Handbook 5.0.2. The Review Manager 5.3 software was applied for meta-analysis of the included literature. RESULTS A total of 17 articles meeting the requirements were selected, including a total of 1,911 subjects. Meta-analysis results showed that the serum free triiodothyronine (FT3) levels in patients was greatly reduced after selenium supplementation compared to placebo treatment (MD =-0.40; 95% confidential interval (CI): -0.70--0.10; Z=2.61; P=0.009). Serum free thyroxine (FT4) levels and anti-thyroid peroxidase antibody (TPOAb) levels were also significantly reduced (MD = -0.76; 95% CI: -1.58--0.07; Z=1.79; P=0.07), and anti-thyroid peroxidase antibody (TPOAb) level was decreased observably (MD =-150.25; 95% CI: -04.06--96.43; Z=5.47; P<0.00001). The thyroid stimulating hormone (TSH) levels (MD =0.06; 95% CI: -0.53-0.66; Z=0.21; P=0.83) and anti-thyroglobulin antibody (TGAb) levels (MD =17.19; 95% CI: -254.86-289.25; Z=0.12; P=0.90) were not significantly different between the experimental group and the control group. CONCLUSIONS Selenium-containing drugs were effective in treating AITD patients, and greatly reduced the levels of FT3, FT4, and TPOAb in AITD patients. These results suggested that selenium level had a great effect on AITD and selenium supplementation showed a very important effect on AITD.