Scientific opinion on the tolerable upper intake level for selenium

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. 2023 Jan 20;21(1):e07704. doi: 10.2903/j.efsa.2023.7704

Cohort name Country Reference Follow‐up Funding	Original Cohort (N total) Exclusion criteria Study population (n, sex and age at baseline)	Ascertainment of outcome	Exposure groups^(a) n/person‐years	Incident cases	Model covariates	Results
EPIC France, Germany, Greece, Italy, The Netherlands, Spain, UK Peters et al. (2021) 8.1 yr (median) Nested case–control Public	N = 487 Population sampled: general population Exclusion: missing data on exposure or confounding variables n = 426 Cases: 107 Controls: 319 (matched for age, sex and study centre) Sex: 65.5% females Ethnicity: NR Age (yr, median (range)): 60 (35–70)	Fatal cases of ALS, identified from death certificates; ALS cases defined as those subjects for whom “motor neuron disease” (G12.2 according to ICD, v. 10) was reported as an immediate, antecedent, or underlying cause of death	Erythrocyte Se (ng/g, geo. mean SD) Controls: 117.7 ± 1.31 Cases: 115 ± 1.25 n, per tertile T1 ≤ 104: 141 T2 > 104 ≤ 123: 140 T3 > 123: 145	Incident cases, n per tertile T1: 32 T2: 38 T3: 37	Cigarette smoking, BMI, physical activity, alcohol consumption, and education.	ALS mortality, OR (95% CI) T1: 1.00 [Ref] T2: 1.31 (0.74, 2.31) T3: 1.21 (0.65, 2.25) p _trend, linear = 0.374 p _trend, spline = 0.850 Exclusion of deaths within first 3 yrs did not substantially change the results
Rivalta + Reggio Emilia Italy Vinceti et al. (2019) 29 yr Prospective cohort Public	N = 97,780 Population sampled: subjects continuously residing in Rivalta from 1974 to 1985, exposed to high‐Se‐contaminated tap water (n = 2,065) and unexposed municipal population as controls (n = 95,715) n = 97,780 Sex (% F): Exposed: 51 Unexposed: 53 Ethnicity: NR Age (yr): 5–95+	Fatal and non‐fatal cases of ALS ascertained from death records (since 1986), registries of the neurological department (since 1986), hospital discharge data (since 1993), records of riluzole prescription (since 2001); data from the local ALS registry (since 2009)	Se in tap water (inorganic Se), μg/L Exposed: 8–10 Unexposed: < 1 person‐years, per group: G1, exposed cohort: 50,100 G2, unexposed cohort: 2,233,963	Incident cases, n G1: 7 G2: 112 By period, 1986–1994/1995–2015 G1: 4/3 G2: 21/91 By sex, M/F G1: 3/4 G2: 73/39 Incident cases, n per 100,000 person‐years G1: 14 G2: 5	Age, gender and calendar year, education and occupation	Incidence rate ratio (IRR) for ALS (95% CI) in exposed group (G1) compared to unexposed group (G2) Overall 2.8 (1.3, 6) By period 1986–1994: 8.2 (2.7, 24.7) 1995–2015: 1.5 (0.5, 4.7) By sex F: 5.1 (1.8, 14.3) M: 1.7 (0.5, 5.4)

Cohort name

Country

Reference

Follow‐up

Funding

Original Cohort (N total)

Exclusion criteria

Study population (n, sex and age at baseline)

Ascertainment of outcome

Exposure groups^(a)

n/person‐years

Incident cases

Model covariates

Results

EPIC

France, Germany, Greece, Italy, The Netherlands, Spain, UK

Peters et al. (2021)

8.1 yr (median)

Nested case–control

Public

N = 487

Population sampled: general population

Exclusion: missing data on exposure or confounding variables

n = 426

Cases: 107

Controls: 319 (matched for age, sex and study centre)

Sex: 65.5% females

Ethnicity: NR

Age (yr, median (range)): 60 (35–70)

Fatal cases of ALS, identified from death certificates; ALS cases defined as those subjects for whom “motor neuron disease” (G12.2 according to ICD, v. 10) was reported as an immediate, antecedent, or underlying cause of death

Erythrocyte Se (ng/g, geo. mean SD)

Controls: 117.7 ± 1.31

Cases: 115 ± 1.25

n, per tertile

T1 ≤ 104: 141

T2 > 104 ≤ 123: 140

T3 > 123: 145

Incident cases, n per tertile

T1: 32

T2: 38

T3: 37

Cigarette smoking, BMI, physical activity, alcohol consumption, and education.

ALS mortality, OR (95% CI)

T1: 1.00 [Ref]

T2: 1.31 (0.74, 2.31)

T3: 1.21 (0.65, 2.25)

p _trend, linear = 0.374

p _trend, spline = 0.850

Exclusion of deaths within first 3 yrs did not substantially change the results

Rivalta + Reggio Emilia

Italy

Vinceti et al. (2019)

29 yr

Prospective cohort

Public

N = 97,780

Population sampled: subjects continuously residing in Rivalta from 1974 to 1985, exposed to high‐Se‐contaminated tap water (n = 2,065) and unexposed municipal population as controls (n = 95,715)

n = 97,780

Sex (% F):

Exposed: 51

Unexposed: 53

Ethnicity: NR

Age (yr): 5–95+

Fatal and non‐fatal cases of ALS

ascertained from death records (since 1986), registries of the neurological department (since 1986), hospital discharge data (since 1993), records of riluzole prescription (since 2001); data from the local ALS registry (since 2009)

Se in tap water (inorganic Se), μg/L

Exposed: 8–10

Unexposed: < 1

person‐years, per group:

G1, exposed cohort: 50,100

G2, unexposed cohort:

2,233,963

Incident cases, n

G1: 7

G2: 112

By period, 1986–1994/1995–2015

G1: 4/3

G2: 21/91

By sex, M/F

G1: 3/4

G2: 73/39

Incident cases, n per 100,000 person‐years

G1: 14

G2: 5

Age, gender and calendar year, education and occupation

Incidence rate ratio (IRR) for ALS (95% CI) in exposed group (G1) compared to unexposed group (G2)

Overall

2.8 (1.3, 6)

By period

1986–1994: 8.2 (2.7, 24.7)

1995–2015: 1.5 (0.5, 4.7)

By sex

F: 5.1 (1.8, 14.3)

M: 1.7 (0.5, 5.4)

ALS: Amyotrophic Lateral Sclerosis; EPIC: European Prospective Investigation into Cancer and Nutrition; ICD: International Classification of Diseases; NR: not reported; PREADVISE: Prevention of Alzheimer's Disease with Vitamin E and Selenium; RCT: randomised controlled trail; SELECT: Selenium and Vitamin E Cancer Prevention Trial; yr: year.

(a) Mean ± SD (range), unless specified otherwise.