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	Original Cohort (N total) Exclusion criteria Study population (n, sex and age at baseline^(a))	Ascertainment of outcome	Exposure groups^(a) n	Results
China Yang et al. (1989a) Cross‐sectional	N = 349 Population sampled: individuals living is a seleniferous area in Enshi County, China Exclusion criteria: NR n = 237 Sex: M and F Age (yr): 1–71+	Morphological changes in fingernails used as the main criteria for the presence of selenosis in the ‘high Se’ area. Selenosis was categorised in: (++) persistent or ongoing fingernail disease over yr; (+) fingernail thickening and stratifying + ≥ 1 of the following signs: history of severe hair or nail loss; deformed or brittle fingernails; distinct transverse or longitudinal ridges of the nails; white area at the base of the nail; persistent fall of brow hair and itchiness of shaded skin OR the presence of ≥ 4 of the latter signs.	Whole blood Se	N cases with signs, per category: (++) 6 (+) 54 Whole blood Se of 5 individuals with long‐persisting, distinct clinical signs, ranged from 1.054 to 1.854 mg/L. Minimal whole blood Se of 1.054 mg/L taken as the marginal level for Se toxicity; equivalent to 910 μg/d based on equation from Yang et al. (1989b)
China Yang et al. (1989a) Cross‐sectional Sub‐study on children dental health	N = NR Population sampled: children from “high”, “medium” and “low” Se sites in Enshi County, China Exclusion criteria: NR n = 402 Sex: NR Age (yr): 7–14	Mottled enamel teeth and dental caries; methods NR	Whole blood Se (mg/L) Low: 0.13 ± 0.02; n = 163 Medium: 0.37 ± 0.32; n = 108 High: 1.57 ± 0.44; n = 131	N cases (%) with mottled enamel teeth/dental caries, per Se site: Low: 0 (0%)/39 (23.9%) Medium: 53 (49.1%)/9 (8.3%) High: 125 (95.4%)/3 (2.3%)
CARUSO Project Brazil Lemire et al. (2012) Cross‐sectional	N = 448 Population sampled: Population living in the Lower Tapajós River region of the Brazilian Amazon, with a local traditional diet that includes important Se sources. Exclusion criteria: Pregnant and breastfeeding women, reported stroke, taking psychotropic medication, missing data for blood or plasma biomarkers. n = 407 Sex (% F): 50 Age (yr): 39.9 ± 14.3	A nurse without the information of Se exposure of the individuals, performed clinical examinations an examination of the clinical dermal (hair, body hair, fingernails, toenails and skin), garlic odour breath and dermal signs of Se toxicity. Alopecia and early hair damage (hair shininess and split hairs) were evaluated on a gradient (absent, mild, more than mild, and important). Nails abnormalities, the number of fingernail and toenail whitlows and the presence specific nails damage were examined and noted. General skin irritations were noted and specific skin‐related signs of selenosis on different parts of the body were also carefully examined.	Whole blood Se (μg/L; median, max): 228.4, 1,500.2 Plasma Se (μg/L; median, max): 134.8, 913.2 Normal Whole blood < 560 μg/L Plasma < 328 μg/L N = 360 High Whole blood ≥ 560 < 1,000 μg/L Plasma ≥ 328 < 520 μg/L N = 15 Very high Whole blood ≥ 1,000 μg/L Plasma ≥ 520 μg/L N = 11	N cases with signs, per Se group Hair dry and brittle, easily broken at scalp Normal 2 High 0 Very high 0 Sparse head hair Normal 21 High 1 Very high 0 Sparse body hair Normal 163 High 9 Very high 4 Abnormal fingernails Normal 149 High 7 Very high 5 Fingernails with whitlow Normal 52 High 1 Very high 2 Longitudinal/transversal fingernail streaks Normal 4/3 High 0/0 Very high 1/0 Symmetric fingernail thickening and stratifying Normal 8 High 0 Very high 0 Deformed and brittle fingernail Normal 8 High 0 Very high 0 Garlic breath Normal 56 High 3 Very high 1
India Chawla et al. (2020) Cross‐sectional	N = 680 Population sampled: Residents of 7 villages pertaining to a seleniferous area in Punjab, India. Exclusion criteria: NR n = 680 Sex (% F): 61 Age (yr, median (IQR)): 43 (32–52)	Method to identify clinical signs of selenosis NR	Serum Se (μg/L, median (IQR)) 171.30 (111.7, 400.5) N = 238 Hair Se (μg/g, median (IQR)) 1.25 (0.75, 2.42) N = 521 Nail Se Se (μg/g, median (IQR)) 5.69 (4.37, 8.42) N = 513	N cases with sign present/sign not present; OR (95% CI) of clinical signs according to Se exposure biomarkers above the median compared to below the median (ref.) , adjusted for age, sex, socio‐economic status Hair loss Serum Se: 22/97 vs 33/86; 0.61 (0.33, 1.15) Hair Se: 57/203 vs 39/222; 1.69 (1.07, 2.66) Nail Se: 46/211 vs 49/207; 0.92 (0.59, 1.44) Hair abnormalities Serum Se: 72/47 vs 58/61; 1.56 (0.92, 2.65) Hair Se: 57/203 vs 39/222; 2.71 (1.86, 3.96) Nail Se: 46/211 vs 49/207; 1.35 (0.94, 1.95) Nail abnormalities Serum Se: 77/42 vs 55/64; 2.06 (1.21, 3.50) Hair Se: 139/121 vs 78/183; 2.72 (1.88, 3.93) Nail Se: 122/13 vs 89/167; 1.71 (1.19, 2.44) Garlic odour breath Serum Se: 6/113 vs 2/117; 3.45 (0.59, 20.34) Hair Se: 12/249 vs 14/246; 0.88 (0.39, 1.96) Nail Se: 3.48 (1.37, 8.85) Selenosis* 7/102 vs 1/109 Serum Se 7.56 (0.87, 65.39) Nail Se 3.48 (0.68, 17.92) *Considered as a collection of all clinical signs linked to overexposure to selenium.
USA Longnecker et al. (1991) Cross‐sectional	N = 142 Population sampled: Year 1: households selected at random from telephone books for western South Dakota and eastern Wyoming’ (n = 49) and ranches with suspected unusually high because of selenosis in livestock (n = 29) Year 2: additional group of subjects suspected of having high Se intakes (because of selenosis in livestock) + ≥ 1 adult in household with serum Se >2. 10 mol/L (n = 64) Exclusion criteria: NR n = 142 Sex (% F): 53 Age: NR	Self‐administered questionnaire to collect data on symptoms of Se toxicity; collected once every season in yr 1; in summer and winter fin yr 2. Photographs of subjects' thumbnails taken with a camera equipped with a macro lens and a ring light; taken once, in summer of yr 1 and yr 2; a board‐certified dermatologist, unaware of the subjects' laboratory results, evaluated the photographs Standardised physical examinations performed by a physician, focusing on dermatologic and neurologic examinations (e.g. signs of interest included muscle weakness, asymmetrical reflexes, hyperreflexia, abnormal sensory examination, dermatitis, and nail loss or markings); performed in summer of yr 1	Whole blood Se (μmol/kg) 4.04 ± 1.39 (2.30–8.54) n = 141 sampled once every season in yr 1; in summer and winter in yr 2 Toenail Se (μmol/kg) 19.7 ± 7.3 (10.6–48.4) n = 142 collected once every season in yr 1; in summer and winter in yr 2 Diet Se (μmol/d) 3.04 ± 1.81 (0.86–9.20) n = 76 based on 2‐d duplicate portions method, once every season in yr 1; in summer and winter in yr 2	*OR (95% CI) of having symptoms more frequently than the median for an increase of 1 SD in Se biomarker, adjusted for sex, age and smoking Muscle twitches Muscle twitches** Whole blood: 1.17 (0.84,1.64) Nail: 1.10 (0.80,1.51) Diet: 1.28 (0.87,1.88) Paraesthesia Whole blood: 0.64 (0.45,0.93) Nail: 0.73 (0.36,0.80) Diet: 0.52 (0.50,1.05) Lethargy Whole blood: 1.41 (1.01,1.96) Nail: 1.41 (1.02,1.95) Diet: 1.43 (0.98,2.09) Nail breakage/ nail loss Whole blood: 0.72 (0.50, 1.02)/1.22 (0.56, 2.66) Nail: 0.79 (0.56, 1.10)/1.13 (0.52, 2.42) Diet: 0.84 (0.57, 1.23)/0.78 (0.09, 6.59) Dark nail lines/white nail lines Whole blood: 0.77 (0.39, 1.53)/1.09 (0.74, 1.60) Nail: 0.75 (0.39, 1.44)/1.01 (0.67, 1.49) Diet: 0.85 (0.42, 1.72)/1.20 (0.80, 1.78) Hair loss Whole blood 1.13 (0.77, 1.67) Nail 1.04 (0.70, 1.54) Diet 0.96 (0.61, 1.53) Yellowed skin Whole blood 0.38 (0.06, 2.46) Nail 0.50 (0.09, 2.91) Diet 0.86 (0.08, 8.81) Garlic breath Whole blood 1.14 (0.76, 1.73) Nail 1.03 (0.68, 1.56) Diet 1.03 (0.65, 1.63) Dizziness Whole blood 1.20 (0.88, 1.64) Nail 1.29 (0.94, 1.76) Diet 1.17 (0.82, 1.66) *OR (95% CI) of having abnormal findings on photographic examination of thumbnails for an increase of 1 SD in Se toenail, adjusted for sex, age and smoking Leukonychia: 0.95 (0.53, 1.72) Transverse ridging: 0.55 (0.25, 1.25) Longitudinal ridging: 0.57 (0.19, 1.65) Onycholysis*: 1.16 (0.48, 2.79) 1 SD = 1.27 μmol/kg for whole blood; 6.36 μmol/kg for toenail; 1.27 μmol/d for diet N cases with signs, upon physical examination Nail loss, alopecia, liver enlargement, muscle fasciculation: 0 Yellowed sclera: 2; abnormal proprioception: 2; abnormal muscle strength to extend the fingers: 3 (whole‐blood Se <3.18 μmol/kg) Easy epilation: 1 (whole‐blood Se = 3.88 μmol/kg)
Brazil Martens et al. (2015) Cross‐sectional	N = NR Population sampled: Macapá city: children enrolled in public preschool receiving 15‐30 g Brazil nuts 3 d/wk (n = 41); Belém city: control children from public preschool, not receiving Brazil nuts as part of their diet (n = 88); All children spent 5 d/wk at school and had breakfast, lunch and dinner at school. Exclusion: child not enrolled in school in last 7 mo or attendance < 75%. n = 129 Sex (% F): Macapá: 46.3 Belém: 52.3 Age (yr): Macapá: 4.7 ± 0.9 (3.1–6.3) Belém: 4.5 ± 1.2 (2.1–6.6)	Clinical symptoms of selenosis clinically evaluated by a doctor; symptoms included changes to and loss of nails and hair, skin lesions, unusual garlic odour breath, nervous system defects, and gastrointestinal disorders (nausea, vomiting).	Mean Se intake (μg/d, median (range)) Macapá (n = 41): 155.3 (98.7–195.3) Belém (n = 88): 44.4 (33.9–53.2) Based on 7‐d duplicate portions method Plasma Se (μg/L) Macapá (n = 41): 107.29 ± 27.15 (73.0–172.0) Belém (n = 41): 83.56 ± 23.32 (47.0–142.0) Hair Se (μg/g) Macapá (n = 41): 0.89 ± 0.24 (0.44–1.35) Belém (n = 41): 0.31 ± 0.10 (0.12–0.50) Toe‐ and fingernail Se (μg/g) Macapá (n = 41): 3.43 ± 1.81 (0.89–8.43) Belém (n = 41): 1.29 ± 0.52 (0.31–2.16)	No clinical symptoms of selenosis observed in any child.
India Senthilkumaran et al. (2012) Case report	1 woman, healthy, 55 yr old; Consumed “paradise nuts” (Lecythis ollaria) with the intention of preventing cancer	Recovered at the emergency department of Sri Gokulam Hospital, Tamil Nadu	Plasma Se, μg/L: 512 Consumed 10–15 ‘paradise nuts’ per day for 20 days	Patient reported headaches, dizziness, vomiting, and abdominal pain for 5 d before hospital admission; Presented severe alopecia; Greyish discolouration of nails developed on 4th hospital day. At follow‐up after 2 mo, hair started to regrow.

Cohort name

Country

Reference

Original Cohort (N total)

Exclusion criteria

Study population (n, sex and age at baseline^(a))

Ascertainment of outcome

Exposure groups^(a)

Results

China

Yang et al. (1989a)

Cross‐sectional

N = 349

Population sampled: individuals living is a seleniferous area in Enshi County, China

Exclusion criteria: NR

n = 237

Sex: M and F

Age (yr): 1–71+

Morphological changes in fingernails used as the main criteria for the presence of selenosis in the ‘high Se’ area. Selenosis was categorised in:

(++) persistent or ongoing fingernail disease over yr;

(+) fingernail thickening and stratifying + ≥ 1 of the following signs: history of severe hair or nail loss; deformed or brittle fingernails; distinct transverse or longitudinal ridges of the nails; white area at the base of the nail; persistent fall of brow hair and itchiness of shaded skin OR the presence of ≥ 4 of the latter signs.

Whole blood Se

N cases with signs, per category:

(++) 6

(+) 54

Whole blood Se of 5 individuals with long‐persisting, distinct clinical signs, ranged from 1.054 to 1.854 mg/L.

Minimal whole blood Se of 1.054 mg/L taken as the marginal level for Se toxicity; equivalent to 910 μg/d based on equation from Yang et al. (1989b)

China

Yang et al. (1989a)

Cross‐sectional

Sub‐study on children dental health

N = NR

Population sampled: children from “high”, “medium” and “low” Se sites in Enshi County, China

Exclusion criteria: NR

n = 402

Sex: NR

Age (yr): 7–14

Mottled enamel teeth and dental caries; methods NR

Whole blood Se (mg/L)

Low: 0.13 ± 0.02; n = 163

Medium: 0.37 ± 0.32; n = 108

High: 1.57 ± 0.44; n = 131

N cases (%) with mottled enamel teeth/dental caries, per Se site:

Low: 0 (0%)/39 (23.9%)

Medium: 53 (49.1%)/9 (8.3%)

High: 125 (95.4%)/3 (2.3%)

CARUSO Project

Brazil

Lemire et al. (2012)

Cross‐sectional

N = 448

Population sampled: Population living in the Lower Tapajós River region of the Brazilian Amazon, with a local traditional diet that includes important Se sources.

Exclusion criteria: Pregnant and breastfeeding women, reported stroke, taking psychotropic medication, missing data for blood or plasma biomarkers.

n = 407

Sex (% F): 50

Age (yr): 39.9 ± 14.3

A nurse without the information of Se exposure of the individuals, performed clinical examinations an examination of the clinical dermal (hair, body hair, fingernails, toenails and skin), garlic odour breath and dermal signs of Se toxicity. Alopecia and early hair damage (hair shininess and split hairs) were evaluated on a gradient (absent, mild, more than mild, and important). Nails abnormalities, the number of

fingernail and toenail whitlows and the presence specific nails damage were examined and noted. General skin

irritations were noted and specific skin‐related signs of selenosis on different parts of the body were also carefully examined.

Whole blood Se (μg/L; median, max): 228.4, 1,500.2

Plasma Se (μg/L; median, max): 134.8, 913.2

Normal

Whole blood < 560 μg/L

Plasma < 328 μg/L

N = 360

High

Whole blood ≥ 560 < 1,000 μg/L

Plasma ≥ 328 < 520 μg/L

N = 15

Very high

Whole blood ≥ 1,000 μg/L

Plasma ≥ 520 μg/L

N = 11

N cases with signs, per Se group

Hair dry and brittle, easily broken at scalp

Normal 2

High 0

Very high 0

Sparse head hair

Normal 21

High 1

Very high 0

Sparse body hair

Normal 163

High 9

Very high 4

Abnormal fingernails

Normal 149

High 7

Very high 5

Fingernails with whitlow

Normal 52

High 1

Very high 2

Longitudinal/transversal fingernail streaks

Normal 4/3

High 0/0

Very high 1/0

Symmetric fingernail thickening and stratifying

Normal 8

High 0

Very high 0

Deformed and brittle fingernail

Normal 8

High 0

Very high 0

Garlic breath

Normal 56

High 3

Very high 1

India

Chawla et al. (2020)

Cross‐sectional

N = 680

Population sampled: Residents of 7 villages pertaining to a seleniferous area in Punjab, India.

Exclusion criteria: NR

n = 680

Sex (% F): 61

Age (yr, median (IQR)): 43 (32–52)

Method to identify clinical signs of selenosis NR

Serum Se (μg/L, median (IQR))

171.30 (111.7, 400.5)

N = 238

Hair Se (μg/g, median (IQR))

1.25 (0.75, 2.42)

N = 521

Nail Se Se (μg/g, median (IQR))

5.69 (4.37, 8.42)

N = 513

N cases with sign present/sign not present; OR (95% CI) of clinical signs according to Se exposure biomarkers above the median compared to below the median (ref.) , adjusted for age, sex, socio‐economic status

Hair loss

Serum Se: 22/97 vs 33/86; 0.61 (0.33, 1.15)

Hair Se: 57/203 vs 39/222; 1.69 (1.07, 2.66)

Nail Se: 46/211 vs 49/207; 0.92 (0.59, 1.44)

Hair abnormalities

Serum Se: 72/47 vs 58/61; 1.56 (0.92, 2.65)

Hair Se: 57/203 vs 39/222; 2.71 (1.86, 3.96)

Nail Se: 46/211 vs 49/207; 1.35 (0.94, 1.95)

Nail abnormalities

Serum Se: 77/42 vs 55/64; 2.06 (1.21, 3.50)

Hair Se: 139/121 vs 78/183; 2.72 (1.88, 3.93)

Nail Se: 122/13 vs 89/167; 1.71 (1.19, 2.44)

Garlic odour breath

Serum Se: 6/113 vs 2/117; 3.45 (0.59, 20.34)

Hair Se: 12/249 vs 14/246; 0.88 (0.39, 1.96)

Nail Se: 3.48 (1.37, 8.85)

Selenosis*

7/102 vs 1/109

Serum Se 7.56 (0.87, 65.39)

Nail Se 3.48 (0.68, 17.92)

*Considered as a collection of all clinical signs linked to overexposure to selenium.

USA

Longnecker et al. (1991)

Cross‐sectional

N = 142

Population sampled:

Year 1: households selected at

random from telephone books for western South Dakota and

eastern Wyoming’ (n = 49) and ranches with suspected unusually high because of selenosis

in livestock (n = 29)

Year 2: additional group of subjects suspected of having high Se intakes (because of selenosis in livestock) + ≥ 1 adult in household with serum Se >2. 10 mol/L (n = 64)

Exclusion criteria: NR

n = 142

Sex (% F): 53

Age: NR

Self‐administered questionnaire to collect data on symptoms of Se toxicity; collected once every season in yr 1; in summer and winter fin yr 2.

Photographs of subjects' thumbnails taken with a camera equipped with a macro lens and a ring light; taken once, in summer of yr 1 and yr 2; a board‐certified dermatologist, unaware of the subjects' laboratory results, evaluated the photographs

Standardised physical examinations performed by

a physician, focusing on dermatologic and neurologic examinations (e.g. signs of interest included muscle weakness, asymmetrical reflexes, hyperreflexia,

abnormal sensory examination, dermatitis, and nail loss or markings); performed in summer of yr 1

Whole blood Se (μmol/kg)

4.04 ± 1.39 (2.30–8.54)

n = 141

sampled once every season in yr 1; in summer and winter in yr 2

Toenail Se (μmol/kg)

19.7 ± 7.3 (10.6–48.4)

n = 142

collected once every season in yr 1; in summer and winter in yr 2

Diet Se (μmol/d)

3.04 ± 1.81 (0.86–9.20)

n = 76

based on 2‐d duplicate portions method, once every season in yr 1; in summer and winter in yr 2

OR (95% CI) of having symptoms more frequently than the median for an increase of 1 SD* in Se biomarker, adjusted for sex, age and smoking

Muscle twitches

Whole blood: 1.17 (0.84,1.64)

Nail: 1.10 (0.80,1.51)

Diet: 1.28 (0.87,1.88)

Paraesthesia

Whole blood: 0.64 (0.45,0.93)

Nail: 0.73 (0.36,0.80)

Diet: 0.52 (0.50,1.05)

Lethargy

Whole blood: 1.41 (1.01,1.96)

Nail: 1.41 (1.02,1.95)

Diet: 1.43 (0.98,2.09)

Nail breakage/ nail loss

Whole blood: 0.72 (0.50, 1.02)/1.22 (0.56, 2.66)

Nail: 0.79 (0.56, 1.10)/1.13 (0.52, 2.42)

Diet: 0.84 (0.57, 1.23)/0.78 (0.09, 6.59)

Dark nail lines/white nail lines

Whole blood: 0.77 (0.39, 1.53)/1.09 (0.74, 1.60)

Nail: 0.75 (0.39, 1.44)/1.01 (0.67, 1.49)

Diet: 0.85 (0.42, 1.72)/1.20 (0.80, 1.78)

Hair loss

Whole blood 1.13 (0.77, 1.67)

Nail 1.04 (0.70, 1.54)

Diet 0.96 (0.61, 1.53)

Yellowed skin

Whole blood 0.38 (0.06, 2.46)

Nail 0.50 (0.09, 2.91)

Diet 0.86 (0.08, 8.81)

Garlic breath

Whole blood 1.14 (0.76, 1.73)

Nail 1.03 (0.68, 1.56)

Diet 1.03 (0.65, 1.63)

Dizziness

Whole blood 1.20 (0.88, 1.64)

Nail 1.29 (0.94, 1.76)

Diet 1.17 (0.82, 1.66)

OR (95% CI) of having abnormal findings on photographic examination of thumbnails for an increase of 1 SD* in Se toenail, adjusted for sex, age and smoking

Leukonychia: 0.95 (0.53, 1.72)

Transverse ridging: 0.55 (0.25, 1.25)

Longitudinal ridging: 0.57 (0.19, 1.65)

Onycholysis: 1.16 (0.48, 2.79)

* 1 SD = 1.27 μmol/kg for whole blood; 6.36 μmol/kg for toenail; 1.27 μmol/d for diet

N cases with signs, upon physical examination

Nail loss, alopecia, liver enlargement, muscle fasciculation: 0

Yellowed sclera: 2; abnormal proprioception: 2; abnormal muscle strength to extend the fingers: 3 (whole‐blood Se <3.18 μmol/kg)

Easy epilation: 1 (whole‐blood Se = 3.88 μmol/kg)

Brazil

Martens et al. (2015)

Cross‐sectional

N = NR

Population sampled:

Macapá city: children enrolled in public preschool receiving 15‐30 g Brazil nuts 3 d/wk (n = 41);

Belém city: control children from public preschool, not receiving Brazil nuts as part of their diet (n = 88);

All children spent 5 d/wk at school and had breakfast, lunch and dinner at school.

Exclusion: child not enrolled in school in last 7 mo or attendance < 75%.

n = 129

Sex (% F):

Macapá: 46.3

Belém: 52.3

Age (yr):

Macapá: 4.7 ± 0.9 (3.1–6.3)

Belém: 4.5 ± 1.2 (2.1–6.6)

Clinical symptoms of selenosis clinically evaluated by a doctor; symptoms included changes to and loss of nails and hair, skin lesions, unusual garlic odour breath, nervous system defects, and gastrointestinal disorders (nausea, vomiting).

Mean Se intake (μg/d, median (range))

Macapá (n = 41): 155.3 (98.7–195.3)

Belém (n = 88): 44.4 (33.9–53.2)

Based on 7‐d duplicate portions method

Plasma Se (μg/L)

Macapá (n = 41): 107.29 ± 27.15 (73.0–172.0)

Belém (n = 41): 83.56 ± 23.32 (47.0–142.0)

Hair Se (μg/g)

Macapá (n = 41): 0.89 ± 0.24 (0.44–1.35)

Belém (n = 41): 0.31 ± 0.10 (0.12–0.50)

Toe‐ and fingernail Se (μg/g)

Macapá (n = 41): 3.43 ± 1.81 (0.89–8.43)

Belém (n = 41): 1.29 ± 0.52 (0.31–2.16)

No clinical symptoms of selenosis observed in any child.

India

Senthilkumaran et al. (2012)

Case report

1 woman, healthy, 55 yr old;

Consumed “paradise nuts” (Lecythis ollaria) with the intention of preventing cancer

Recovered at the emergency department of Sri Gokulam Hospital, Tamil Nadu

Plasma Se, μg/L: 512

Consumed 10–15 ‘paradise nuts’ per day for 20 days

Patient reported headaches, dizziness, vomiting, and abdominal pain for 5 d before hospital admission;

Presented severe alopecia;

Greyish discolouration of nails developed on 4th hospital day.

At follow‐up after 2 mo, hair started to regrow.

CI: confidence interval; d: day; F: females; mo: month; M: males; N: number of participants; NA: not applicable; NR: not reported; OR: odds ratio; SD: standard deviation; Se: selenium; USA: United States of America; wk: week; yr: year.

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