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Mediterranean Diet and Physical Activity Nudges versus Usual Care in Women with Rheumatoid Arthritis: Results from the MADEIRA Randomized Controlled Trial.
Papandreou, P, Gioxari, A, Daskalou, E, Grammatikopoulou, MG, Skouroliakou, M, Bogdanos, DP
Nutrients. 2023;15(3)
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Rheumatoid arthritis (RA) is one of the most common autoimmune diseases. Various dietary patterns, including the Mediterranean diet (MD), and individual nutrients including certain types of fatty acids and vitamin D, have been investigated for their potential associations with the development and prognosis of RA. The aim of this study was to evaluate the effect of a personalized MD plan delivered through a clinical decisions support system (CDSS) platform versus usual care, in women with an RA diagnosis. This study is a single-blind (statistician), two-arm randomised controlled trial. Patients (n = 40 women with RA) were randomly allocated to the intervention or the control arm. Results show that a 12-week personalized MD plan, paired with physical activity (PA) promotion and delivered with the support of CDSS was successful in improving adherence to the MD, disease activity, PA levels, and a plethora of cardiometabolic outcomes among female patients with RA. Furthermore, disease activity was also associated with body mass index. The overall combined prevalence of overweight and obesity in the sample was high, namely 35% and 10%, respectively. Authors conclude that greater adherence to the MD was associated with an ameliorated dietary fat intake, body weight, body composition, and lower disease activity state. Thus, authors suggest that the adoption of the MD by patients with RA appears to be a feasible anti-inflammatory regime.
Abstract
In rheumatoid arthritis (RA), diet quality and nutritional status have been shown to impact the disease activity and adherence to the Mediterranean diet (MD) has been suggested as an anti-inflammatory regime to improve disease status and reduce cardiovascular risk. The Mediterranean DiEt In Rheumatoid Arthritis (MADEIRA) was a single-blind (statistician), two-arm randomized clinical trial, investigating the effects of a 12-week lifestyle intervention, including a personalized isocaloric MD plan with the promotion of physical activity (PA), supported through a clinical decision support systems (CDSS) platform, versus usual care in women with RA. Forty adult women with RA on remission were randomly allocated (1:1 ratio) to either the intervention or the control arm. The intervention group received personalized MD plans and lifestyle consultation on improving PA levels, whereas the controls were given generic dietary and PA advice, based on the National Dietary Guidelines. The primary outcome was that the difference in the MD adherence and secondary outcomes included change in disease activity (DAS28), anthropometric indices (BodPod), dietary intake, PA, vitamin D concentrations, and blood lipid profiles after 12 weeks from the initiation of the trial. At 3 months post-baseline, participants in the MD arm exhibited greater adherence to the MD compared with the controls (p < 0.001), lower DAS28 (p < 0.001), favorable improvements in dietary intake (p = 0.001), PA (p = 0.002), body weight and body composition (p < 0.001), blood glucose (p = 0.005), and serum 1,25(OH)2D concentrations (p < 0.001). The delivery of the MD and PA promotion through CDSS nudges in women with RA in an intensive manner improves the MD adherence and is associated with beneficial results regarding disease activity and cardiometabolic-related outcomes, compared with the usual care.
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Modulating the Gut Microbiome in Multiple Sclerosis Management: A Systematic Review of Current Interventions.
Tsogka, A, Kitsos, DK, Stavrogianni, K, Giannopapas, V, Chasiotis, A, Christouli, N, Tsivgoulis, G, Tzartos, JS, Giannopoulos, S
Journal of clinical medicine. 2023;12(24)
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Multiple sclerosis (MS) is an autoimmune disease caused by the altered immune system mistakenly attacking the central nervous system. While genetics play a leading causative role in the manifestation of this disease, other contributing environmental factors can also exist, such as a disruption in the intestinal microbial composition. Previous research has shown that the bidirectional communication between the brain's and gut's health, also known as the gut-brain axis, may contribute to the prognosis of MS. Modulating gut microbial composition can be a therapeutic strategy in MS patients to manage symptoms and prevent disease progression. This systematic review assessed different protocols for modulating gut microbial composition, including dietary modifications, probiotic use, intermittent fasting, and faecal microbial transplantation. The review included thirteen studies that compared the effects of the above gut microbial modulation intervention protocols in MS patients with healthy participants. While different dietary modification strategies improved MS symptoms, probiotic supplementations and intermittent fasting reduced inflammation, and faecal microbial transplantation showed promising positive effects in a few reports. Due to the methodological limitations of the included studies, further robust studies are required to evaluate the beneficial effects of gut microbial modulation strategies in reducing the symptoms of MS patients. However, healthcare professionals can use the results of this study to understand the benefits of gut microbial modulation in MS patients.
Abstract
This review attempted to explore all recent clinical studies that have investigated the clinical and autoimmune impact of gut microbiota interventions in multiple sclerosis (MS), including dietary protocols, probiotics, fecal microbiota transplantation (FMT), and intermittent fasting (IF). Methods: Thirteen studies were held between 2011 and 2023 this demonstrated interventions in gut microbiome among patients with MS and their impact the clinical parameters of the disease. These included specialized dietary interventions, the supply of probiotic mixtures, FMT, and IF. Results: Dietary interventions positively affected various aspects of MS, including relapse rates, EDSS disability scores, MS-related fatigue, and metabolic features. Probiotic mixtures showed promising results on MS-related fatigue, EDSS parameters, inflammation; meanwhile, FMT-though a limited number of studies was included-indicated some clinical improvement in similar variables. IF showed reductions in EDSS scores and significant improvement in patients' emotional statuses. Conclusions: In dietary protocols, clinical MS parameters, including relapse rate, EDSS, MFIS, FSS, and MSQoL54 scales, were significantly improved through the application of a specific diet each time. Probiotic nutritional mixtures promote a shift in inflammation towards an anti-inflammatory cytokine profile in patients with MS. The administration of such mixtures affected disability, mood levels, and quality of life among patients with MS. FMT protocols possibly demonstrate a therapeutic effect in some case reports. IF protocols were found to ameliorate EDSS and FAMS scores. All interventional means of gut microbiome modulation provided significant conclusions on several clinical aspects of MS and highlight the complexity in the relationship between MS and the gut microbiome.
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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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Associations between Dynamic Vitamin D Level and Thyroid Function during Pregnancy.
Wang, H, Wang, HJ, Jiao, M, Han, N, Xu, J, Bao, H, Liu, Z, Ji, Y
Nutrients. 2022;14(18)
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Thyroid hormones play a vital role in regulating metabolism. Adequate thyroid hormone levels are also critical during pregnancy for optimal fetal growth and development. The foetus is dependent on maternal thyroid hormones until its own thyroid gland matured in the second half of pregnancy. Furthermore, pregnancy impacts thyroid function leading to an increased demand for thyroid hormones. Thyroid disease has been associated with Vitamin D deficiency. During pregnancy, both thyroid disorders and Vitamin D deficiency can have adverse effects on pregnancy and pregnancy outcomes, hence a potential link between Vitamin D status and thyroid function has been postulated. To fill the gaps in previous research, this retrospective cohort study aimed to explore the associations between Vitamin D status and thyroid function throughout the pregnancy, in each trimester. The analysis of hospital data collected in Beijing demonstrated an association between Vitamin D levels and thyroid function throughout pregnancy. Such interlink appeared to be dynamic and changed depending on the stage of pregnancy. The author's findings affirmed that maintenance of adequate Vitamin D levels supports normal thyroid function which is an important nutritional strategy for a healthy pregnancy.
Abstract
Optimal Vitamin D (VitD) status and thyroid function are essential for pregnant women. This study aimed to explore associations between dynamic VitD status and thyroid function parameters in each trimester and throughout the pregnancy period. Information on all 8828 eligible participants was extracted from the Peking University Retrospective Birth Cohort in Tongzhou. Dynamic VitD status was represented as a combination of deficiency/sufficiency in the first and second trimesters. Thyroid function was assessed in three trimesters. The associations between VitD and thyroid function were assessed by multiple linear regression and generalized estimating equation models in each trimester and throughout the pregnancy period, respectively. The results indicated that both free thyroxine (fT4; β = 0.004; 95%CI: 0.003, 0.006; p < 0.001) and free triiodothyronine (fT3; β = 0.009; 95%CI: 0.004, 0.015; p = 0.001) had positive associations with VitD status in the first trimester. A VitD status that was sufficient in the first trimester and deficient in the second trimester had a lower TSH (β = -0.370; 95%CI: -0.710, -0.031; p = 0.033) compared with the group with sufficient VitD for both first and second trimesters. In conclusion, the associations between VitD and thyroid parameters existed throughout the pregnancy. Maintaining an adequate concentration of VitD is critical to support optimal thyroid function during pregnancy.
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The Impact of Vitamin D Supplementation on the IFNγ-IP10 Axis in Women with Hashimoto's Thyroiditis Treated with Levothyroxine: A Double-blind Randomized Placebo-controlled Trial.
Robat-Jazi, B, Mobini, S, Chahardoli, R, Mansouri, F, Nodehi, M, Esfahanian, F, Saboor Yaraghi, AA
Iranian journal of allergy, asthma, and immunology. 2022;21(4):407-417
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Hashimoto’s thyroiditis is an autoimmune disease characterized by the presence of antibodies against thyroid proteins such as thyroperoxidase (TPO) and thyroglobulin (TG), the local accumulation of inflammatory cells and immune-mediated destruction of the thyroid gland. Disease manifestation is due to a genetic disposition but is also influenced by several environmental factors, including stress, smoking, infections, and levels of nutrients like iodine, selenium and vitamin D. Many cells of the immune system have receptors for Vitamin D and thus have the potential to be influenced by Vitamin D. Indeed, numerous findings demonstrated that vitamin D can exert anti-inflammatory effects on the immune system. This double-blind, randomized, placebo-controlled trial investigated 40 Hashimoto's thyroiditis subjects and the effect of Vitamin D supplementation on various markers of the immune system that mediate the inflammatory response as part of the interferon-gamma-induced protein 10 (IFNγ-IP10) axis. 20 of the enrolled candidates received 50000 IU of Vitamin D (cholecalciferol) once a week – an equivalent to about 7140 IU per day - over three months. The other half received a placebo. All candidates had a fixed dose of thyroid hormone replacement levothyroxine for the duration of the trial. Before and after the intervention several blood biomarkers were investigated relating to Vitamin D levels, D-receptors, immune activity and inflammation. Upon completion of the trial, the intervention group who supplemented Vitamin D had significantly higher Vitamin D levels, which had increased from an average of 25.29 ng/ml to 50.65ng/ml. In addition, several inflammatory factors were significantly decreased. These findings affirmed Vitamin D’s ability to favourably regulate the IFNγ-IP10 axis, which could slow disease progression. This effect may also be useful for the management of other autoimmune disorders involving IP10 overproduction, which attracts other inflammatory cells. More studies in larger groups would help to get more information on other variables not considered in this trial.
Abstract
Hashimoto's thyroiditis (HT) results from chemoattraction of inflammatory cells toward the thyroid gland by inducing the production of interferon-gamma (IFNγ)-induced protein 10 (IP10) by T helper (Th) 1 cells. Vitamin D may suppress the IFNγ-IP10 axis, but this new function of vitamin D has not yet been investigated in HT patients. In an intervention and control group, patients received 50000 IU cholecalciferol or placebo every week for three months, respectively. The CD4+ T cells of 40 patients were isolated, and the mRNA expression levels of vitamin D receptor (VDR), peroxisome proliferator-activated receptors (PPAR)-α, and PPAR-γ genes were determined by real-time PCR. ELISA method was used to determine serum levels of vitamin D, tumor necrosis factor-alpha (TNF-α), IFN-γ, and IP10. Vitamin D levels in the intervention group were significantly higher than in the placebo group after supplementation. PPAR-α and PPAR-γ gene expression levels did not differ significantly between the two groups. The serum levels of IP10, IFNγ, and TNF-α decreased significantly in the vitamin D group, as well as in the placebo group. During this study, vitamin D levels significantly increased in the intervention group and inflammatory factors decreased. Based on the similar results obtained in the placebo group, further studies with larger sample sizes and longer intervention times are recommended.
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Helping psoriasis from the inside out
Dr. Mark Hyman is a practicing family physician and an internationally recognised leader, speaker, educator, and advocate in the field of Functional Medicine. He is the founder and director of The UltraWellness Centre, the Head of Strategy and Innovation of the Cleveland Clinic Centre for Functional Medicine, a thirteen-time New York Times bestselling author, and Board President for Clinical Affairs for The Institute for Functional Medicine.
2022
Abstract
In this podcast episode Dr Hyman speaks to Dr Todd LePine about the various causes of psoriasis including genetics, diet, environmental factors, toxins, and streptococcus bacteria, highlighting that psoriasis is not a skin condition but rather a systemic one. They review both the conventional and functional medicine approaches to manage psoriasis, sharing interesting patient case studies and solutions that have worked which primarily centre around addressing gut health. Key functional laboratory tests to identify the root causes of psoriasis are reviewed but they highlight that it is also important to discuss stress, sleep and sun exposure with patients due to their impact on the immune system and subsequent gut integrity.
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Persistent Anti-Borrelia IgM Antibodies without Lyme Borreliosis in the Clinical and Immunological Context.
Markowicz, M, Reiter, M, Gamper, J, Stanek, G, Stockinger, H
Microbiology spectrum. 2021;9(3):e0102021
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Borrelia burgdorferi (BD) specific Immunoglobulin (Ig) antibodies are a diagnostic key for infection and Lyme’s disease. Generally, IgM is reflective of recent infection and converts to IgG after several weeks during disease progression or inadequate treatment. Yet, in the early phase of infection, not all cases present with antibodies and at the same time, both IgM and IgG can persist in healthy people after tick exposure or treatment. This study sought to investigate further the common phenomenon of persistence of IgM, regardless of symptomatic BD infection. The study examined the serum of 59 predominantly female patients, that showed persistent IgM antibodies in the absence of IgG. The majority of subjects experienced non-specific symptoms, and half of them had a history of antibiotic treatment, yet IgM persisted. The observation went on for >6 months, thus excluding the likelihood of any acute infection. The results showed that in people with lower IgM count a greater improvement of non-specific symptoms was observed as opposed to those with higher IgM count. Furthermore, the assay identified multiple cross-reactivity patterns from other plants, bacteria and human tissue to the antigen-binding receptor OspC typically used for BD testing. The authors postulate that the phenomena of IgM persistence potentially originates from a previous infection with BD, but may be maintained in some individuals by continuous stimulation with cross-reactive antigens from other sources. This is important knowledge for the interpretation and improvement of testing for BD. Of clinical interest here is that IgM persistence, beyond the acute phase, maybe no longer be reflective of the original BD infection. And in such cases, non-specific symptoms may be sustained by other triggers such as foods, other microorganisms and autoimmunity.
Abstract
The aim of the study was to investigate the etiology of persistent IgM antibodies against Borrelia burgdorferi sensu lato (sl) and to analyze their association with nonspecific symptoms. The study group comprised individuals with persistent IgM antibodies in the absence of IgG. The relation between ELISA values and time elapsed since past erythema migrans (EM) was analyzed. Previous antibiotic treatments were assessed. The association between persistent IgM and nonspecific symptoms was evaluated statistically. Specificity of IgM antibodies for outer surface protein C (OspC) of B. burgdorferi sl was examined by immunoblotting. Further, we investigated the cross-reactivity with Borrelia-unrelated proteins. Fifty-nine patients (46 women; 78%) were included in the study group. The mean IgM-ELISA values did not change significantly during follow-up (median 6.2 months). The mean ELISA value in the study group was dependent on time elapsed since past EM. Nonspecific symptoms improved significantly more often in patients with lower IgM ELISA results. Persistent IgM antibodies were specific for the C-terminal PKKP motif of OspC. Cross-reacting C-terminal PKKP antigens from both human and prokaryotic origins were identified. We demonstrate that the C-terminal PKKP motif plays a main role for the reactivity of persistent Borrelia IgM toward OspC. However, cross-reactivity to other eukaryotic and/or prokaryotic antigens may hamper the specificity of OspC in the serological diagnosis of Lyme borreliosis. Lack of improvement of nonspecific symptoms was associated with higher IgM ELISA values. IMPORTANCE The reactivity of human IgM with the outer surface protein C (OspC) of Borrelia burgdorferi sensu lato is frequently used to detect Borrelia specific IgM in commercial immunoassays, and such antibodies usually occur in the early phase of the infection. We identified a group of individuals with persistent Borrelia IgM without symptoms of Lyme borreliosis. We used their sera to demonstrate that the C-terminal epitope of OspC binds the IgM. Strikingly, we found that the same epitope occurs also in certain proteins of human and environmental origin; the latter include other bacteria and food plants. Our experimental data show that these Borrelia-unrelated proteins cross-react with the OpsC-specific IgM. This knowledge is important for the development of serologic assays for Lyme borreliosis and provides a cross-reactive explanation for the persistence of Borrelia-IgM.
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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.
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Another Chicken and Egg Story: Systematic Review on Lichen Planus as a Precursor for Celiac Disease in Adult Population.
Khan, S, Patel, S, M, S, Hamid, P
Cureus. 2020;12(8):e9526
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Lichen planus is a rare, chronic, inflammatory skin condition affecting the mucous membranes. It is immunological, sometimes regarded as autoimmune, and associated with some autoimmune disorders and infectious diseases. The presence of an autoimmune disorder increases the likelihood of the co-occurrence or development of other autoimmune conditions, and such is the case in Coeliac disease (CD). CD is an autoimmune condition leading to damage to the gastrointestinal tissue. CD can remain undetected in many patients, yet skin manifestations can occur long before or together with gastrointestinal damage. Hence the authors of this study were interested in how CD and Lichen planus related to each other and whether Lichen planus can be an early marker for CD. For this 2389 studies were assessed, with the inclusion of nine in the final assessment - a mix of case reports, observational studies, and systematic and traditional reviews. The authors could identify a correlation between lichen planus and CD but could not establish causation or a clear relationship between the two conditions. In conclusion, the authors advocated for more studies on larger population groups. Of clinical interest is the author's suggestion that in LP patients with signs of mouth ulcers and skin eruptions testing for CD and a gluten-free diet is warranted and could help manage disease progression.
Abstract
Celiac disease is receiving much attention due to the gluten-free diet trend. Many health-conscious individuals practice a gluten-free diet, even if they do not have celiac disease. As it is an autoimmune disorder, it is associated with many other autoimmune diseases. We were interested in one skin condition, another autoimmune disorder lichen planus as a correlative factor for celiac disease. The following systematic review may give some clues. We searched online resources including PubMed, PubMed Central, Cochrane library, and Google scholar for systematic reviews, traditional reviews, randomized controlled trials, and meta-analysis on celiac disease and lichen planus. We included human studies published in peer-reviewed journals in the English language. After reviewing 2389 initial results of our search, we excluded 1250 duplicates, 1108 abstracts, 42 irrelevant articles. We assessed the remaining 26 articles for their quality using various quality assessment tools. After the quality assessment, we included nine final articles in our systematic review. Out of these nine studies, there were four systematic reviews, one traditional review, two case reports, and two observational studies. Only two articles had exclusively studied the specific association between celiac and lichen planus. The remaining studies included data that gave an overall association between other skin manifestations of celiac disease. From our study, we could not establish the relationship between celiac disease and lichen planus. We need more case-control studies and clinical trials with a larger population to get conclusive data. From current data, we can conclude that both immunological processes correlate but there is no causation. There is also a need for clinical trials to explore the exacerbation of lichen planus due to celiac disease.