J Food Bioact

Journal of Food Bioactives, ISSN 2637-8752 print, 2637-8779 online

Journal website www.isnff-jfb.com

Original Research

Volume 35, September 2026, pages 81-89

Effects of egg white hydrolysate on facial swelling: a randomized, double-blind, placebo-controlled, crossover trial

Figure 1. Size-exclusion chromatogram of peptides in EWH. Molecular weights were estimated based on the retention times of standard proteins and peptides. Arrows A, B, C, and D indicate estimated elution position of molecular weights of 6,000, 3,000, 1,000, and 500 Da, respectively. Peak area > 6,000, 3,000–6,000, 1,000–3,000, 500–1,000, < 500 were calculated.

Figure 2. CONSORT flow diagram of participants throughout the study. A = the test product, B = placebo

**Table 1.** Composition of test product and placebo per daily intake (mg / 2 tablets / day)
Ingredients	Test product	Placebo
EWH (Peptide content)	250 (191.2)	0
Microcrystalline cellulose	233	483
Reduced maltose syrup	90	90
Anti-caking agent	9.0	9.0
Magnesium stearate	12	12
Disintegrant	6.0	6.0

Table 1. Composition of test product and placebo per daily intake (mg / 2 tablets / day)

Ingredients

Test product

Placebo

EWH (Peptide content)

250 (191.2)

Microcrystalline cellulose

233

483

Reduced maltose syrup

Anti-caking agent

9.0

Magnesium stearate

Disintegrant

6.0

Table 2. Schedule of enrollment, interventions, and assessments throughout the clinical trial

Screening (Scr)

BL-3days

BL-2days

BL-1day

Period I

Wash out (2 weeks)

Period II

Briefing Session

Scr-3days

Scr-2days

Scr-1day

Scr

Enrollment

Baseline (BL) Day1

Day5

Day6

Day7

Day8 (Assessment)

BL-3days

BL-2days

BL-1day

Baseline (BL) Day1

Day5

Day6

Day7

Day8 (Assessment)

Scr = Screening, BL = Baseline. “Scr-3days” indicates 3days before screening. “BL-3days” indicates 3days before baseline. “•” indicates an item performed during the specified period.”⟷” indicates an item performed daily by the participants throughout the specified period. AM refers to the period within 60 min after waking up, and PM refers to the period between 17:00 and 18:00.

Registration

•

Eligibility screening

•

Informed consent

•

Other procedures

•

Intervention

EWH/Placebo

←------------------------------→

Assessment

VAS

•

Measurement of calf

•

Measurement of ankle

•

Physical measurements

•

Urinalysis

•

Blood chemistry

•

Daily log

←------------------------------→

Dietary assessment

•

**Table 3.** Molecular weight distribution of peptides in EWH
Molecular weight range (Da)	Peak area (%)
>6,000	1
3,000–6,000	4
1,000–3,000	20
500–1,000	18
<500	57
Total	100

Table 3. Molecular weight distribution of peptides in EWH

Molecular weight range (Da)

Peak area (%)

>6,000

3,000–6,000

1,000–3,000

500–1,000

<500

Total

100

**Table 4.** Baseline characteristics of participants
Item	Enrolled participants	Analyzed participants
Data are presented as means ± standard deviation, and P-value was calculated using the student’s t-test. VAS was assessed on a 100 mm scale, where 0 mm represents “not at all” and 100 mm represents “very much.” A = the test product, B = placebo
Age (years)	43.4 ± 10.2	42.5 ± 11.1	0.707	44.4 ± 10.5	44.0 ± 11.0	0.870
Height (cm)	161.7 ± 6.7	163.4 ± 7.0	0.272	161.3 ± 6.4	164.3 ± 7.5	0.093
Body weight (kg)	62.2 ± 7.4	61.1 ± 9.7	0.570	62.4 ± 7.4	62.4 ± 9.5	0.976
BMI (kg/m²)	23.8 ± 2.5	22.7 ± 2.3	0.068	24.0 ± 2.6	23.0 ± 2.1	0.102
Systolic blood pressure (mmHg)	113.5 ± 18.8	113.5 ± 18.1	1.000	111.9 ± 14.4	115.8 ± 18.5	0.363
Diastolic blood pressure (mmHg)	74.5 ± 13.4	74.8 ± 12.4	0.901	73.9 ± 10.8	76.3 ± 12.8	0.432
VAS score for facial swelling (mm)	69.6 ± 12.9	69.5 ± 9.9	0.953	69.6 ± 12.2	68.7 ± 9.4	0.744

Table 4. Baseline characteristics of participants

Item

Enrolled participants

Analyzed participants

Sequence AB Group (n = 38)

Sequence BA Group (n = 38)

P value

Sequence AB Group (n = 31)

Sequence BA Group (n = 30)

P value

Data are presented as means ± standard deviation, and P-value was calculated using the student’s t-test. VAS was assessed on a 100 mm scale, where 0 mm represents “not at all” and 100 mm represents “very much.” A = the test product, B = placebo

Age (years)

43.4 ± 10.2

42.5 ± 11.1

0.707

44.4 ± 10.5

44.0 ± 11.0

0.870

Height (cm)

161.7 ± 6.7

163.4 ± 7.0

0.272

161.3 ± 6.4

164.3 ± 7.5

0.093

Body weight (kg)

62.2 ± 7.4

61.1 ± 9.7

0.570

62.4 ± 7.4

62.4 ± 9.5

0.976

BMI (kg/m²)

23.8 ± 2.5

22.7 ± 2.3

0.068

24.0 ± 2.6

23.0 ± 2.1

0.102

Systolic blood pressure (mmHg)

113.5 ± 18.8

113.5 ± 18.1

1.000

111.9 ± 14.4

115.8 ± 18.5

0.363

Diastolic blood pressure (mmHg)

74.5 ± 13.4

74.8 ± 12.4

0.901

73.9 ± 10.8

76.3 ± 12.8

0.432

VAS score for facial swelling (mm)

69.6 ± 12.9

69.5 ± 9.9

0.953

69.6 ± 12.2

68.7 ± 9.4

0.744

**Table 5.** Subjective outcomes measured during the AM assessments
Item	Time point	EWH	Placebo	Group comparison	P value
BL = Baseline, SD = standard deviation, EMM = estimated marginal means, SE = standard error, 95% CI- = 95% confidence interval (lower bound), 95% CI+ = 95% confidence interval (upper bound), ⊿ = difference in estimated marginal means. P < 0.05, * P < 0.01 compared with the placebo group at the same time point (between-group comparison based on a general linear mixed model). VAS was assessed on a 100 mm scale, where 0 mm represents “not at all” and 100 mm represents “very much”.
Facial swelling (mm)	BL	66.3	10.4	66.3	1.4	63.7	69.0	65.5	10.6	65.5	1.4	62.8	68.2	0.8	1.4	−1.9	3.5	–	0.995	0.830
Day7	54.8	22.1	54.8	2.6	49.6	59.9	58.9	18.6	58.8	2.6	53.7	64.0	−4.1	1.9	−7.9	−0.2	0.037*	0.085	0.870
(Day7-BL)	−11.5	19.8	−11.6	2.2	−15.9	−7.2	−6.6	14.9	−6.7	2.2	−11.0	−2.3	−4.9	2.2	−9.3	−0.5	0.029*	0.030*	0.783
Swelling around the eyes (mm)	BL	62.7	17.5	62.6	2.3	58.0	67.2	62.7	18.4	62.7	2.3	58.2	67.3	−0.1	2.4	−5.0	4.8	–	0.601	0.162
Day7	56.1	22.4	56.1	2.6	50.8	61.3	59.9	19.7	59.8	2.6	54.6	65.1	−3.8	2.1	−7.9	0.4	0.073	0.051	0.845
(Day7-BL)	−6.5	16.7	−6.6	2.1	−10.7	−2.4	−2.8	16.5	−2.9	2.1	−7.0	1.2	−3.7	2.7	−9.0	1.7	0.176	0.019*	0.257
Lack of definition in facial contour (mm)	BL	59.5	18.3	59.4	2.2	55.1	63.8	63.1	16.0	63.1	2.2	58.8	67.5	−3.7	2.4	−8.5	1.1	–	0.310	0.243
Day7	55.9	21.0	55.8	2.5	50.7	60.8	57.6	19.7	57.5	2.5	52.5	62.5	−1.8	2.0	−5.9	2.3	0.390	0.019*	0.310
(Day7-BL)	−3.6	13.8	−3.7	2.0	−7.6	0.2	−5.5	17.4	−5.6	2.0	−9.5	−1.7	1.9	2.6	−3.2	7.1	0.456	0.017*	0.776
Calf swelling (mm)	BL	62.0	22.5	61.9	2.6	56.7	67.1	65.0	18.3	64.9	2.6	59.7	70.1	−3.0	2.2	−7.4	1.4	–	0.145	0.479
Day7	56.8	22.8	56.6	2.7	51.2	62.0	58.1	21.5	58.0	2.7	52.6	63.3	−1.3	2.4	−6.0	3.4	0.576	0.006**	0.743
(Day7-BL)	−5.2	16.8	−5.3	2.1	−9.4	−1.1	−6.9	16.4	−7.0	2.1	−11.1	−2.8	1.7	2.9	−4.2	7.5	0.567	0.022*	0.791
Ankle swelling (e.g., shoes or socks feel tight) (mm)	BL	58.7	24.1	58.6	2.7	53.3	64.0	62.8	17.5	62.7	2.7	57.4	68.1	−4.1	2.3	−8.8	0.5	–	0.154	0.504
Day7	54.2	22.1	54.1	2.7	48.8	59.5	57.9	21.3	57.8	2.7	52.5	63.2	−3.7	2.4	−8.4	1.0	0.124	0.013*	0.670
(Day7-BL)	−4.5	15.3	−4.5	2.0	−8.4	−0.6	−4.9	15.8	−4.9	2.0	−8.8	−1.0	0.4	2.4	−4.4	5.3	0.864	0.092	0.822
Coldness in hands and feet (mm)	BL	39.3	23.7	39.3	3.1	33.2	45.3	38.9	24.7	39.0	3.1	33.0	45.1	0.2	3.4	−6.5	7.0	–	0.341	0.011*
Day7	33.7	23.3	33.6	3.1	27.5	39.7	34.8	24.8	34.9	3.1	28.8	40.9	−1.2	2.9	−7.1	4.6	0.670	0.686	0.008**
(Day7-BL)	−5.6	25.6	−5.7	2.9	−11.5	0.1	−4.1	20.1	−4.2	2.9	−10.0	1.6	−1.5	4.1	−9.7	6.7	0.717	0.097	0.816
Temporary depressed mood due to prominent blue dark circles (mm)	BL	45.5	24.5	45.5	3.1	39.2	51.7	45.3	24.3	45.3	3.1	39.0	51.5	0.2	2.3	−4.5	4.9	–	0.801	0.765
Day7	41.3	23.6	41.3	3.1	35.1	47.4	41.2	24.1	41.2	3.1	35.1	47.4	0.0	2.1	−4.2	4.3	0.987	0.880	0.939
(Day7-BL)	−4.2	17.2	−4.2	2.1	−8.3	−0.1	−4.0	15.1	−4.0	2.1	−8.2	0.1	−0.2	2.8	−5.8	5.5	0.953	0.846	0.760
Temporary depressed mood due to a tired-looking face (mm)	BL	55.7	20.7	55.6	2.7	50.3	61.0	55.4	21.3	55.4	2.7	50.0	60.8	0.2	2.5	−4.9	5.3	–	0.902	0.577
Day7	48.5	21.9	48.5	2.9	42.7	54.3	49.7	23.3	49.7	2.9	43.9	55.5	−1.2	2.0	−5.3	2.8	0.547	0.703	0.223
(Day7-BL)	−7.2	16.7	−7.2	2.3	−11.7	−2.6	−5.7	18.7	−5.7	2.3	−10.3	−1.2	−1.4	2.7	−6.9	4.0	0.601	0.683	0.702

Table 5. Subjective outcomes measured during the AM assessments

Item

Time point

EWH

Placebo

Group comparison

P value

Mean

EMM

95% CI-

95% CI+

Mean

EMM

95% CI-

95% CI+

⊿

95% CI-

95% CI+

Treatment effect

Sequence effect

Period effect

BL = Baseline, SD = standard deviation, EMM = estimated marginal means, SE = standard error, 95% CI- = 95% confidence interval (lower bound), 95% CI+ = 95% confidence interval (upper bound), ⊿ = difference in estimated marginal means. *P < 0.05, ** P < 0.01 compared with the placebo group at the same time point (between-group comparison based on a general linear mixed model). VAS was assessed on a 100 mm scale, where 0 mm represents “not at all” and 100 mm represents “very much”.

Facial swelling (mm)

66.3

10.4

66.3

1.4

63.7

69.0

65.5

10.6

65.5

1.4

62.8

68.2

0.8

1.4

−1.9

3.5

–

0.995

0.830

Day7

54.8

22.1

54.8

2.6

49.6

59.9

58.9

18.6

58.8

2.6

53.7

64.0

−4.1

1.9

−7.9

−0.2

0.037*

0.085

0.870

(Day7-BL)

−11.5

19.8

−11.6

2.2

−15.9

−7.2

−6.6

14.9

−6.7

2.2

−11.0

−2.3

−4.9

2.2

−9.3

−0.5

0.029*

0.030*

0.783

Swelling around the eyes (mm)

62.7

17.5

62.6

2.3

58.0

67.2

62.7

18.4

62.7

2.3

58.2

67.3

−0.1

2.4

−5.0

4.8

–

0.601

0.162

Day7

56.1

22.4

56.1

2.6

50.8

61.3

59.9

19.7

59.8

2.6

54.6

65.1

−3.8

2.1

−7.9

0.4

0.073

0.051

0.845

(Day7-BL)

−6.5

16.7

−6.6

2.1

−10.7

−2.4

−2.8

16.5

−2.9

2.1

−7.0

1.2

−3.7

2.7

−9.0

1.7

0.176

0.019*

0.257

Lack of definition in facial contour (mm)

59.5

18.3

59.4

2.2

55.1

63.8

63.1

16.0

63.1

2.2

58.8

67.5

−3.7

2.4

−8.5

1.1

–

0.310

0.243

Day7

55.9

21.0

55.8

2.5

50.7

60.8

57.6

19.7

57.5

2.5

52.5

62.5

−1.8

2.0

−5.9

2.3

0.390

0.019*

0.310

(Day7-BL)

−3.6

13.8

−3.7

2.0

−7.6

0.2

−5.5

17.4

−5.6

2.0

−9.5

−1.7

1.9

2.6

−3.2

7.1

0.456

0.017*

0.776

Calf swelling (mm)

62.0

22.5

61.9

2.6

56.7

67.1

65.0

18.3

64.9

2.6

59.7

70.1

−3.0

2.2

−7.4

1.4

–

0.145

0.479

Day7

56.8

22.8

56.6

2.7

51.2

62.0

58.1

21.5

58.0

2.7

52.6

63.3

−1.3

2.4

−6.0

3.4

0.576

0.006**

0.743

(Day7-BL)

−5.2

16.8

−5.3

2.1

−9.4

−1.1

−6.9

16.4

−7.0

2.1

−11.1

−2.8

1.7

2.9

−4.2

7.5

0.567

0.022*

0.791

Ankle swelling (e.g., shoes or socks feel tight) (mm)

58.7

24.1

58.6

2.7

53.3

64.0

62.8

17.5

62.7

2.7

57.4

68.1

−4.1

2.3

−8.8

0.5

–

0.154

0.504

Day7

54.2

22.1

54.1

2.7

48.8

59.5

57.9

21.3

57.8

2.7

52.5

63.2

−3.7

2.4

−8.4

1.0

0.124

0.013*

0.670

(Day7-BL)

−4.5

15.3

−4.5

2.0

−8.4

−0.6

−4.9

15.8

−4.9

2.0

−8.8

−1.0

0.4

2.4

−4.4

5.3

0.864

0.092

0.822

Coldness in hands and feet (mm)

39.3

23.7

39.3

3.1

33.2

45.3

38.9

24.7

39.0

3.1

33.0

45.1

0.2

3.4

−6.5

7.0

–

0.341

0.011*

Day7

33.7

23.3

33.6

3.1

27.5

39.7

34.8

24.8

34.9

3.1

28.8

40.9

−1.2

2.9

−7.1

4.6

0.670

0.686

0.008**

(Day7-BL)

−5.6

25.6

−5.7

2.9

−11.5

0.1

−4.1

20.1

−4.2

2.9

−10.0

1.6

−1.5

4.1

−9.7

6.7

0.717

0.097

0.816

Temporary depressed mood due to prominent blue dark circles (mm)

45.5

24.5

45.5

3.1

39.2

51.7

45.3

24.3

45.3

3.1

39.0

51.5

0.2

2.3

−4.5

4.9

–

0.801

0.765

Day7

41.3

23.6

41.3

3.1

35.1

47.4

41.2

24.1

41.2

3.1

35.1

47.4

0.0

2.1

−4.2

4.3

0.987

0.880

0.939

(Day7-BL)

−4.2

17.2

−4.2

2.1

−8.3

−0.1

−4.0

15.1

−4.0

2.1

−8.2

0.1

−0.2

2.8

−5.8

5.5

0.953

0.846

0.760

Temporary depressed mood due to a tired-looking face (mm)

55.7

20.7

55.6

2.7

50.3

61.0

55.4

21.3

55.4

2.7

50.0

60.8

0.2

2.5

−4.9

5.3

–

0.902

0.577

Day7

48.5

21.9

48.5

2.9

42.7

54.3

49.7

23.3

49.7

2.9

43.9

55.5

−1.2

2.0

−5.3

2.8

0.547

0.703

0.223

(Day7-BL)

−7.2

16.7

−7.2

2.3

−11.7

−2.6

−5.7

18.7

−5.7

2.3

−10.3

−1.2

−1.4

2.7

−6.9

4.0

0.601

0.683

0.702