Evidence Trace, complete trial record
In plain terms
In plain terms: Selenium (Selenomethionine) shows early signals in human research but the evidence is limited -- small trials, surrogate endpoints, or not yet independently replicated. It is an emerging area, not yet a proven one.
Selenium (Selenomethionine)
C
Limited: small, mixed or unreplicated trials
The endpoint this grade is based on: Surrogate biomarker endpoint, Thyroid peroxidase antibody levels in autoimmune thyroiditis, lower across several meta-analyses and one 412-patient trial, a surrogate whose fall has not changed thyroid function, levothyroxine dose or quality of life (C). Long-term supplementation in adults who are not deficient was tested in trials of 1,312 to 35,533 people: no cancer benefit and a signal of more type 2 diabetes (D Route 2). The trials were not selected for selenium deficiency, and the Cochrane review found no clear influence of baseline status on outcomes.
The evidence as the record states it
Thyroid, the graded use. Wichman et al. (Thyroid, 2016; PMID 27702392): 16 controlled trials; thyroid peroxidase antibodies lower at 3, 6 and 12 months in patients on levothyroxine and at 3 months in untreated patients, quality of evidence generally low, more adverse effects on selenium. Huwiler et al. (Thyroid, 2024; PMID 38243784): 35 studies; antibodies and TSH lower, moderate certainty overall, adverse effects comparable to control. Zhang et al. (Medicine (Baltimore), 2025; PMID 40898469): 21 randomized trials confirming the antibody fall, with selenomethionine outperforming other forms. Larsen et al. (Eur Thyroid J, 2024; PMID 38215286), CATALYST: 412 patients with autoimmune thyroiditis on levothyroxine, 200 mcg/day as selenium-enriched yeast for 12 months; quality of life, the primary outcome, improved equally on selenium and placebo. Winther et al. (Endocrine, 2017; PMID 27683225): systematic review; no change in TSH, thyroid ultrasound or quality of life in untreated patients, very low to low certainty. Replete adults, the D row. Clark et al. (JAMA, 1996; PMID 8971064), the Nutritional Prevention of Cancer trial: 1,312 patients with prior skin cancer in low-selenium areas of the eastern United States, 200 mcg/day; the primary endpoints, basal and squamous cell skin cancer, were not reduced, and the secondary cancer findings were not confirmed afterward. Stranges et al. (Ann Intern Med, 2007; PMID 17620655): the same trial's secondary analysis, type 2 diabetes more frequent on selenium (hazard ratio 1.55), concentrated in the highest tertile of baseline plasma selenium. Lippman et al. (JAMA, 2009; PMID 19066370), SELECT: 35,533 men, 200 mcg/day L-selenomethionine, this record's form; no reduction in prostate or any other cancer, with a nonsignificant rise in type 2 diabetes. Thompson et al. (J Natl Cancer Inst, 2016; PMID 27530657), Sel/Cel: 1,621 adults after adenoma removal, 200 mcg/day as selenized yeast; no adenoma prevention and a diabetes signal in older participants. Vinceti et al. (Cochrane, 2018; PMID 29376219): high-certainty evidence of no effect on cancer incidence (RR 1.01), a slight increase in type 2 diabetes, and no clear influence of baseline selenium status. Alehagen et al. (2013; PMID 22626835) gave selenium combined with coenzyme Q10 and cannot grade selenium alone; context only. Grade C, the thyroid use, with the headline following it; replete-adult supplementation D on Route 2.
PMID 8971064 PMID 19066370 PMID 22626835 PMID 17620655 PMID 38243784 PMID 40898469 PMID 27702392 PMID 29376219 PMID 38215286 PMID 27683225 PMID 27530657
Evidence by specific use
Autoimmune thyroiditis (TPO antibodies)
Grade C
Replicated on the antibody surrogate. Wichman et al. (Thyroid, 2016; PMID 27702392), 16 trials; Huwiler et al. (Thyroid, 2024; PMID 38243784), 35 studies, moderate certainty; and Zhang et al. (Medicine (Baltimore), 2025; PMID 40898469), 21 randomized trials, all found thyroid peroxidase antibodies lower on selenium, and the 412-patient CATALYST trial found them lower at 12 months (Larsen et al., Eur Thyroid J, 2024; PMID 38215286). What did not change: quality of life, CATALYST's primary outcome, improved equally on placebo; TSH, thyroid ultrasound and quality of life in untreated patients were unchanged in a systematic review (Winther et al., Endocrine, 2017; PMID 27683225); heterogeneity is extreme and several trials are null. Replication on a surrogate can carry B only when the surrogate is an established stand-in for a clinical outcome, and thyroid peroxidase antibodies are not one; whether their fall changes any clinical outcome remains to be shown. The pooled trials mixed selenomethionine, selenite and selenium yeast. Re-graded C by the editor in October 2026: thyroid peroxidase antibodies are not an established stand-in for a clinical outcome, and their fall has not changed thyroid function, levothyroxine dose or quality of life.
PMID 27702392 PMID 38243784 PMID 40898469 PMID 38215286 PMID 27683225
Long-term supplementation in already-replete adults
Grade D
Tested at scale and no benefit, with a diabetes signal. SELECT gave 200 mcg/day L-selenomethionine, this record's form, to 35,533 men and found no reduction in prostate or any other cancer, with a nonsignificant rise in type 2 diabetes (Lippman et al., JAMA, 2009; PMID 19066370). The Cochrane review found high-certainty evidence of no cancer benefit and a slight diabetes increase (Vinceti et al., 2018; PMID 29376219). The Nutritional Prevention of Cancer trial, run in low-selenium areas, missed its skin cancer primary (Clark et al., 1996; PMID 8971064) and found more type 2 diabetes on selenium, concentrated in those with the highest baseline levels (Stranges et al., 2007; PMID 17620655); Sel/Cel found no adenoma prevention and a diabetes signal in older participants (Thompson et al., 2016; PMID 27530657). For a trace mineral, more is not better. D on Route 2; the diabetes signal is stated as a signal, since in the largest trial it did not reach significance.
PMID 17620655 PMID 19066370 PMID 29376219 PMID 27530657 PMID 8971064
Why Grade C and not Grade B
Grade C reflects early or limited human evidence -- small trials, surrogate endpoints, or preliminary findings not yet independently replicated. The evidence points in a promising direction but does not yet meet the standard for Grade B. A single well-powered, independently replicated trial with a meaningful endpoint would move this to Grade B or higher.
What would move this grade
A well-powered randomized trial with an objective, clinically meaningful primary endpoint and at least one independent replication would support Grade B or higher.
How to track whether this is working
If selenium status is uncertain or supplementation is being used to correct a deficiency, serum or plasma selenium can help document status. Thyroid testing should be guided by the clinical context. If selenium status is already adequate, increasing the dose further should not be treated as a treatment target.