. 2024 Mar 13;34(3):295–313. doi: 10.1089/thy.2023.0556

Table 1.

Study and Participant Characteristics of the 35 Included Randomized Controlled Trials

First author (year)	Study population (age [years]; % female)	Duration (months)	Dose (μg/day), selenium compound	N	Blinding	Comparison	THRT (total study population)	Thyroid status and selenium status at study start	Outcomes included in this review
Anastasilakis (2012)⁵⁵	18–80; 61.6%	3, 6	200, Selenium-methionine	40^a	No	NA	Both	Euthyroid, mildly deficient	TSH,^b fT4,^b fT3,^b TPOAb,^b TGAb^b
Balázs (2008)⁶⁴	Mean 41.4 (I), 42.7 (C); 97.7%	12	200, Selenium-methionine	132	Double	Placebo	Yes	NA, NA	↓ TSH, fT4,^b fT3,^b ↓ TPOAb, = TGAb, = Vol
Bhuyan (2012)⁷⁵	Mean 34 (I), 31 (C); 88.3%	3	200, Sodium selenite	60	Blinded	Placebo	Yes	Euthyroid or overt hypothyroid, NA	↓ TPOAb^c
Bonfig (2010)⁴²	7.6–16.4; 67.3%	12	(1) 100, (2) 200, Sodium selenite	49	No	No treatment	Yes	Overt hypothyroid, NA	= TSH, fT4,^b fT3,^b = TPOAb, = TGAb, = AE
Chakrabarti (2016)⁵²	Mean 39.6 (I), 34.5 (C); 40%	6	200, Selenious acid	60	Participant blinded	Placebo	Yes	Overt hypothyroid, NA	↓ TSH, = fT4, ↓ MDA
De Farias (2015)⁷⁶	20–58; 90.9%	3, 6	200, Selenium-methionine	43	Double	Placebo	Both	Euthyroid or subclinical hypothyroid, severely deficient	= TSH, fT4,^b = T3, = T4, = TPOAb, = TGAb, ↑ GPX
Duntas (2003)⁵⁶	22–61; 86.2%	3, 6	200, Selenium-methionine	65	NA	Placebo	Yes	Subclinical hypothyroid, NA	= TSH, = fT4, = T3, = TPOAb, = TGAb
Eskes (2014)⁶⁵	20–74; 100%	3, 6	200, Sodium selenite	61	Double	Placebo	No	Euthyroid, severely deficient	= TSH, = fT4, = TPOAb, = AE, ↑ SELENOP, = QoL
Esposito (2017)⁵⁸	17–64; 100%	3, 6	166, Selenium-methionine	76	Blinded	Placebo	No	Euthyroid, NA	TSH,^b = fT4,^d ↑ fT3,^d = TPOAb, = Echo, = CXCL-10
Gärtner (2002)⁵⁷	Mean 47.5; 100%	3	200, Sodium selenite	70	Blinded	Placebo	Yes	Euthyroid,^e severely deficient	= TSH, = fT4, = fT3, ↓ TPOAb, ↑ TGAb, = AE, ↑ QoL, ↓ Echo
Hu (2021)⁷⁰	Mean 38.6; 88.9%	3, 6	200, Selenium yeast	90	No	No treatment	No	Euthyroid or subclinical hypothyroid, severely deficient	↓ TSH, = fT4, = fT3, = TPOAb, = TGAb, = AE
Kachouei (2018)⁶⁶	18–60; 64.3%	3	200, Sodium selenite	70	Double	Placebo	Yes	Overt hypothyroid, mildly deficient	↑ GPX, ↑ SELENOP
Karanikas (2008)⁵⁴	19–85; 100%	3	200, Sodium selenite	36	Blinded	Placebo	Yes	Euthyroid,^e severely deficient	= TSH, = fT4, = TPOAb, = TNF-α, = IFN-γ, = CD4, = CD8, = IL-2, = IL-4, = IL-10, = IL-13, ↑ QoL
Karimi (2019)⁶⁹	15–78; 75.8%	3	200, Sodium selenite	66	Patient blinded	Placebo	Both	NA, mildly deficient	= TSH, = TPOAb, = TGAb, = AE
Krysiak (2012)⁴³	18–60; 100%	3, 6	200, Selenium-methionine	164	Double	Placebo	(1) Yes (2) No	Euthyroid, NA	= TSH, = fT4, = fT3, ↓ TPOAb, ↓ TGAb (1), = TGAb (2), = AE
Kyrgios (2019)⁴⁸	4.5–17.8; 80.3%	6	200, Selenium-methionine	71	Double	Placebo	Both	Euthyroid or overt hypothyroid, NA	= TSH, = fT4, ↓ TPOAb, ↓ TGAb, = Vol
Mahmoodianfard (2015)⁶⁷	25–65; 100%	3	200, NA^f	58	Double	Placebo	Yes	Overt hypothyroid. severely deficient	= TSH, = fT4, = T4, = fT3, = T3
Mahmoudi (2021)⁶⁸	18–60; 88.1%	2	200, Selenium yeast	42	Double	Placebo	No	Subclinical hypothyroid, NA	TSH,^b T4,^b T3,^b TPOAb^b
Mantovani (2019)⁵⁰	18–45; 100%, Pregnant	(1) 6, (2) 12 (during/after pregnancy)	83, Selenium-methionine	45	Double	Placebo	Both	Euthyroid, severely deficient	TSH,^b fT4,^b fT3,^b = TPOAb (1), ↓ TPOAb (2), TGAb,^b = AE, = Echo, = Vol, = QoL
Mao (2016)⁴⁹	NA; 100% Pregnant	2, 5	60, Selenium yeast	31	Double	Placebo	No	Euthyroid or subclinical hypothyroid, sufficient	TSH,^b fT4,^b = TPOAb
Nacamulli (2010)⁵⁹	15–75; 85.5%	6, 12	80, Sodium selenite	76	Investigator blinded	No treatment	NA	Euthyroid and subclinical hypothyroid, NA	= TSH, = fT4, = TPOAb, = TGAb, ↓ Echo
Negro (2007)⁵¹	18–36; 100%; Pregnant	∼11 (0, 5, [12]^g Months after delivery)	200, Selenium-methionine	151	Double	Placebo	Both	Euthyroid, severely deficient	↓ TPOAb,^c,d = AE
Negro (2016)⁴⁴	Mean 44 (I), 45 (C); NA	3	(1) 83 (2) 166 (3) 249, Selenium-methionine	80	Double	Placebo	No	Overt hypothyroid, NA	= TSH, = fT4, = CDs
Pilli (2015)⁴⁵	21–65; 100%	6, 12	(1) 80 (2) 160, Selenium-methionine	60	Blinded	Placebo	No	Euthyroid, mildly deficient	= TSH,^d = TPOAb,^d = TGAb, = AE, = Echo, = GPX, = SELENOP, ↓ CXCL-9, ↓ CXCL-10, = CXCL-11 (1), ↓ CXCL-11 (2), ↓ TNF-α (1), = TNF-α (2), ↓ IFN-γ (1), = IFN-γ (2), = QoL
Pirola (2016)⁶¹	18–65; 84.9%	4	83, Selenium-methionine	192	NA	No treatment	No	Subclinical hypothyroid, NA	= TSH, = fT4, ↓ TPOAb
Preda (2017)⁶²	Mean 46.2 (I), 50.5 (C); 100%	3	100, Selenium-methionine	100	NA	NA	NA	Euthyroid, sufficent	↓ TSH, = TPOAb, = GPX
Shabalina (2019)⁴⁰	20–40; 100%	3, 6, 9, 12	200, Selenium-methionine	51	No	No treatment	NA	(1) Euthyroid (2) Subclinical hypothyroid, NA	↓ TSH, ↑ fT4 (1), = fT4 (2), = fT3, = TPOAb,^d = AE, = Echo, = Vol
Sun (2021)⁷¹	20–64; 68.1%	3	100, Selenium yeast	129	No	No treatment	Yes	Overt hypothyroid, NA	= TSH,^d = T4, = T3, = TPOAb, = TGAb, = AE, ↓ IL-2, ↑ IL-10, ↓ TNF-α
Tian (2020)⁷²	>18 (Mean 40.2); 62.5%	3	200, Selenium yeast	32	NA	Placebo	NA	Euthyroid, mildly deficient	= TSH, = TPOAb, = TGAb, = AE, ↓ MDA, ↑ SOD, ↑ TAC
Turker (2006)⁶³	15–77; 100%	3	200, Selenium-methionine	88^a	Blinded	Placebo	Yes	Euthyroid, NA	TSH,^b fT4,^b fT3,^b = TPOAb, = TGAb
Wang (2018)⁴⁶	15–70; 100%	3, 6	200, Selenium yeast	364	Double	Placebo	(1) No (2) Yes	(1) Euthyroid or subclinical hypothyroid (2) Overt hypothyroid, mildly deficient	= TSH, = fT4 (1), ↓ fT4 (2), = TPOAb, = AE, ↓ MDA, ↑ GPX
Wu (2018)⁷³	20–71; 51.3%	2	200, Selenium yeast	80	No	No treatment	Yes	NA, NA	TSH,^b TPOAb,^b TGAb,^b ↑ CD4/CD8, ↑ CD4/CD3, ↑ CD8/CD3
Yu (2017)⁷⁴	10–64; 93.3%	3	400, Selenium yeast	60	No	No treatment	Yes	(1) Euthyroid (2) Overt hypothyroid, severely deficient	TPOAb,^b TGAb,^b = AE, ↓ IL-2, = IL-10
Zhang (2020)⁵³	32–65; 36.2%	4	200, Sodium selenite	94	No	No treatment	Yes	Overt hypothyroid, NA	= fT4, ↑ fT3, ↓ TPOAb, ↓ TGAb, = AE, ↓ TRAb, ↑ CD3, ↑ CD4, ↓ CD8, ↑ CD4/CD8
Zhu (2012)⁴⁷	15–70; 100%	3, 6	200, Selenium yeast	134	Blinded	Placebo	NA	(1) Euthyroid or subclinical hypothyroid (2) Overt hypothyroid, mildly deficient	TSH,^b fT4,^b = TPOAb (1), ↓ TPOAb (2)

^{^a}

Only participants receiving same intervention throughout the entire study considered.

^{^b}

Results not available.

^{^c}

Data estimated from other studies.

^{^d}

Results extracted from graphs.

^{^e}

Participants already on THRT at study start and therefore reported euthyroid at study start.

^{^f}

One intervention group and its corresponding comparison group additionally received 30 mg zinc per day.

^{^g}

Time point 12 months after delivery was not included in our analysis to increase comparability with other studies.

↑, Significant increase; ↓, significant decrease; = , no significant effect; (1) Cohort 1; (2) Cohort 2; (C) Control group; (I) Intervention group receiving selenium supplementation; AE, adverse event; Echo, ultrasound echogenicity; fT3, free triiodothyronine; fT4, free thyroxine; GPX, glutathione peroxidases; IFN-γ, interferon-gamma; IL, interleukin; MDA, malondialdehyde; NA, not reported in publication; QoL, quality of life; SELENOP, selenoprotein P; SOD, superoxide dismutase; T3, total triiodothyronine; T4, total thyroxine; TAC, total antioxidant capacity; TGAb, thyroglobulin antibodies; THRT, thyroid hormone replacement therapy; TNF-α, tumor necrosis factor-alpha; TPOAb, thyroid peroxidase antibodies; TRAb, thyrotropin receptor antibody; TSH, thyrotropin; Vol, thyroid volume.