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Anti-Aging Medicine 7 (4) : 18-25, 2010(c) Japanese Society of Anti-Aging Medicine

Original Article

Effects of Dried Brewer’s Yeast on Skin and QOL: A Single-Blind Placebo-Controlled Clinical Study of 8-Week Treatment

18

Objective: Brewer’s yeast contains vitamins, minerals, amino acids and other nutrients, and has been reported to control intestinal function as well as to exert anti-ulceration, anti-tumor and anti-allergy effects. The present study evaluated the effects of oral treatment with dried brewer’s yeast tablets (study product) on skin in a single-blind placebo-controlled design in humans.Methods: Thirty-two healthy volunteer women (37.0±4.8 years) were allocated as follows: Group E-30 (n=11) were treated with 30 tablets/day of the study product (containing 7,125mg/day of dried brewer’s yeast), Group E-9 (n=10) were given 9 tablets/day of the study product, and the control group (n=11) were given 30 placebo tablets/day. The treatment period was 8 weeks. Two patients prematurely discontinued the study (discontinuation rate: 5.9%) and were excluded from the analyses. The study product (Ebios Tablet®) was provided by Asahi Food & Healthcare Co., Ltd. Before and at 4 and 8 weeks after the study, subjective symptoms were evaluated using the Anti-Aging QOL Common Questionnaire (AAQol) and checking skin symptoms, skin images were analyzed with SK Info (SKI, Integral Co.) and Aphrodite-III (PSI), and skin color (CM-700d, Konica Minolta Sensing, Inc.) and elasticity (Cutometer MPA580, Courage & Khazaka electronic GmbH) were measured.Results: In Group E-30, the AAQol physical symptom “cold skin” score was significantly improved at 8 weeks (p<0.05). The skin symptoms “make-up runs easily” and “desiccated and gritty skin,” as well as the physical symptom “menstruation-related troubles” were improved in a significant and dose-dependent way from the control group (p<0.01). On skin analysis, SKI demonstrated an increase in moisture content (15.4%, p=0.010), decrease in erythema (– 18.3%, p<0.001) and increase in elasticity (13.3%, p=0.003), while PSI revealed an increase in hydration (Total: 14.5%, T zone: 13.7%, U zone: 18.2%, p<0.01) and decrease in pores (– 32.7%, p=0.022). Cutometer analysis showed a dose-dependent increase in skin elasticity, while analysis of skin color showed a decrease in hemoglobin (– 9.5%, p=0.016), improved lightness (– 0.7%, p=0.045) and decrease in redness (– 8.3%, p=0.013). During the study period, no serious adverse events were noted.Conclusion: These results suggest that treatment with dried brewer’s yeast is useful in improving skin condition, e.g. moisture content and elasticity, and also QOL.

Abstract

Sawako Hibino 1), Umenoi Hamada 2), Hozumi Takahashi 2), Miwako Watanabe 3), Naoko Nozato 4), Yoshikazu Yonei 2)

1) Faculty of Health Sciences, Morinomiya University of Medical Sciences

2) Anti-Aging Medical Research Center, Graduate School of Life and Medical Science, Doshisha University

3) Mareesia Garden Clinic

4) Trend Analysis Section, Department of Research & Development, Asahi Breweries Limited.

KEY WORDS: dried brewer’s yeast, freckles, wrinkles, skin elasticity, moisture content of skin

Received: Oct. 27, 2009Accepted: Jan. 21, 2010Published online: Feb. 24, 2010

Introduction Dried products made from the yeast used for brewing beer contain a range of nutrients, including vitamins, minerals, amino acids, dietary fiber, and nucleic acids. Dried brewer’s yeast products are used as quasi-drugs and foods with health claims (foods with nutrient function claims) in Japan. Animal experiments and clinical studies have demonstrated that dried brewer’s yeast is effective in improving diabetes mellitus 1), promoting ferrous iron absorption 2), controlling intestinal functions 3), improving lipid metabolism, e.g. decreasing LDL-cholesterol levels 4), and exerting anti-ulceration 5,6) and anti-tumor effects 7). Several reviews have also appeared 8-12).

We have previously investigated the effects of cosmetics 13), supplements 14,15) and health foods 16) on skin from the viewpoint of Anti-Aging Medicine using common objective parameters using a skin imaging and analyzing device. Here, we investigated the effects of dried brewer’s yeast on human skin and QOL in a single-blind placebo-controlled clinical study.

Associate Prof. Sawako Hibino,Faculty of Health Sciences, Morinomiya University of Medical Sciences

1-26-16, Nanko-Kita, Suminoe-ku, Osaka City, Osaka 559-0034 JapanTel: +81-(0)6-6616-6911 / Fax: +81-(0)6-6616-6912 / E-mail: [email protected]

Prof. Yoshikazu Yonei, M.D., Ph.D.Anti-Aging Medical Research Center, Graduate School of Life and Medical Science, Doshisha University

1-3, Tatara Miyakodani, Kyotanabe city, Kyoto 610-0321 JapanTel & Fax: +81-(0)774-65-6394 / E-mali: [email protected]

Subjects and Methods

Subjects Thirty-four healthy volunteer women (mean age: 36.9±4.7years) were randomly divided into one of three groups, Group E-30 (n=12), Group E-9 (n=11), and a control group (n=11). After excluding one subject each who withdrew from Groups E-30 and E-9 (discontinuation rate 5.9%), 32 subjects were included in the analysis, consisting of 11 in Group E-30, 10 in Group E-9 and 11 in the control group (mean age: 37.0±4.8 years).

Study Design The present study was a single-blind placebo-controlled clinical trial. Groups E-30 and E-9 received 30 tablets/day (containing 7,125mg/day of dried brewer’s yeast) and 9 tablets/day of the study product, respectively, and the control group received 30 placebo tablets/day, for 8 weeks. During this period, subject condition was checked on three predetermined observation days. The study product contained dried brewer’s yeast (Ebios Tablet® 237.5 mg; Asahi Food & Healthcare Co., Ltd., Sumida-ku, Tokyo). Table 1 shows the major nutritional ingredients typically found in dried brewer’s yeast. One placebo tablet (250 mg) contained crystal cellulose (Ceolus UF-F702) at 99% and lubricant (calcium stearate) at 1%. Each subject took the prescribed number of tablets three times daily after meals. The subjects were instructed to take the study product even if they did not have a meal. When they forgot to take the study product, they were instructed as follows: if they noticed the missed dose during the same day, they were to immediately take the missing dose; and if they noticed the missed dose on the following day or later, they were to miss that dose. Regarding lifestyle-related habits, the subjects were instructed to avoid excessive eating, very demanding exercise, and lack of sleep. They were also instructed to continue the same alcohol consumption habits as before. The subjects maintained a “diary” every day. Those responsible for checking the diaries determined if their lifestyle-related habits had changed, and whenever the investigator found anything which required improvement, he/she informed the subject. On each observation day, the subjects recorded their recent health condition in a “Health Condition Report” form.

Evaluation Methods Subjective symptoms were divided into two categories, physical symptoms and mental symptoms, and rated as described in our previous study according to a 5-grade scale ranging from 1 to 5 points using the Anti-Aging QOL Common Questionnaire (AAQol) 17). This Questionnaire was downloaded from the Web site of the Japanese Society of Anti-Aging Medicine (http://www.anti-aging.gr.jp/anti/clinical.html). Facial skin was evaluated at two sites, i.e. the right cheek and the left cheek, for the volume of moisture, sebum, melanin and erythema, as reported previously 13). The amount of moisture contained in the stratum corneum was determined with a skin moisture analyzer (corneometer) (CM825SPANC, Courage & Khazaka electric GmbH, Cologne, Germany) 18) using the phenomenon that the electrical capacitance of the skin varies depending on its moisture content. Sebum volume was determined with a skin sebum analyzer (sebumeter) (SM810SPANC, Courage & Khazaka electric GmbH) 19), which measures changes in transmittance through a dedicated film. The volume of melanin in

the skin and degree of erythema were measured with a mexameter (MX18, Courage & Khazaka electric GmbH), which irradiates the skin with light of a specific wavelength and measures the reflected light using a light diode to calculate the melanin and erythema indices 18). These parameters were recorded with an SK Info® (Integral Corporation, Shinjuku-ku, Tokyo) (hereinafter referred to as SKI), which integrates various measurement devices. Skin images were analyzed with the Skin Diagnosis System Aphrodite-III system (PSI Co., Ltd., Seoul, Korea) (hereinafter referred to as PSI) to evaluate oil content, total moisture content, excess keratin, pores, and wrinkles at the corner of the eye. Skin color was determined with a spectrophotometer (CM-700d,

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Table 1 Major nutritional ingredients typically found in dried brewer’s yeast*

(1) General composition(%)

Crude protein

Mineral

Carbohydrates

(soluble nitrogen-free substances)

Fiber

Fat

Moisture

p - aminobenzoic acid

Choline

Pantothenic acid

Vitamin B12

Inositol

-

-

-

-

-

-

-

-

-

360

80

1000

100

80

3.6

50

10

40

21

22

100

6

0.1

0.5

37

6

25

-

-

-

-

-

800

5300

350

0.004

5000

9

3500

20

0.001

2700

-

-

-

10

3

9

1

1

4

-

-

-

-

-

-

2.1

-

-

3.0

6.8

1.5

10.4

3.2

2.1

4.7

2.2

1.5

3.9

0.1

5.6

2.6

1.0

1.3

1.8

(2) Vitamins (µg/g)

Thiamine (B1)

Riboflavin (B2)

Nicotinic acid

Pyridoxine (B6)

Folic acid

Biotin

Glucan

Mannan

-

1

0.9

0.8

253 -

-

8

6

6

4

(4) Carbohydrates (%)

Glycogen

Trehalose

Ergosterol - 1.40.2

(5) Lipid (%)

Fat

Phospholipid

Calcium

Magnesium

Silica

-

-

-

59

48

2.5

45

28

0.1

-

-

-

4.5

8.1

1.6

1.0

4.0

0.1

(6) Inorganic ingredients (%)

Phosphorus

Potassium

Sodium

Cobalt

Chrome

Selenium

-

5

0.5

109 0.5

-

0.16

0.20.1

(7) Trace ingredients (mg/100g)

Copper

Zinc

Manganese

64 –76 of previous N

-

-

-

9

0.5

1

3

0.2

0.5

-

-

-

-

-

-

-

-

-

3.1

7.2

4.5

1.6

2.5

4.3

0.9

4.9

4.8

2.1

2.6

2.6

0.6

1.0

1.9

0.5

2.2

2.7

(3) Nitrogen-containing ingredients (%)

Pure protein

RNA

DNA

Glutathione

Composition of amino acids

Isoleucine

Leucine

Lysine

Methionine

Phenylalanine

Threonine

Tryptophan

Valine

Alanine

Arginine

Aspartic acid

Cystine

Glutamic acid

Glycine

Histidine

Proline

Serine

Tyrosine

* Content may vary to some extent since this is a natural product

Konica Minolta Sensing, Inc., Sakai-city, Osaka). As previously reported 20), skin elasticity was determined with a Cutometer (MPA580, Courage & Khazaka electric GmbH) 21). Skin hydration was evaluated with a moisture content analyzer (corneometer) (CM825, Courage & Khazaka electric GmbH) 22). The present study was performed between March 6 and May 2, 2009. The climate condition around the study area was shown in Table 2 23). All study participants received an explanation regarding how to take the study product either by a documented information form or by participation in an explanatory meeting at the medical institution where this study was performed (Mareesia Garden Clinic, Shinjuku-ku, Tokyo). The study subjects understood that even if they had given consent to participate in the study, they were free to express the desire to withdraw from the study on their own volition at any time during the study period without being disadvantaged in any way.

Ethical Considerations and Declaration of No Commercial Relationship The study was performed at a third party institution in compliance with the ethical principles of the Declaration of Helsinki and the Personal Information Protection Law, and by reference to the “Ordinance regarding the Good Clinical Practice (GCP)” (MHW Ordinance No. 28 dated March 27, 1997). At the medical institution which performed the study, an ethical committee for clinical studies held meetings to review the ethical justification and validity of the study. This study was approved by the committee and conducted according to the approved protocol. Through the authority of Doshisha University, the laboratory of the authors was financially supported by Asahi Food & Healthcare Co., Ltd. and Asahi Breweries Foundation (Sumida-ku, Tokyo) for this study. The authors have no commercial relationship with companies related to the field of the study. The activities of the laboratory are annually declared to the Committee of “Conflicts of Interests”.

Statistical Analysis Statistical analyses were performed using the statistical analysis software Dr.SPSSII (SPSS Japan Inc., Shibuya-ku, Tokyo) and Excel Tokei (Social Survey Research Information Co., Ltd., Shinjuku-ku, Tokyo). ANOVA, paired t-test for comparisons before and after treatment, inter-group analyses and analysis of correlations were all two-tailed, and results were considered significant at the <5% level.

Results

Results of the Questionnair Comparison of scores before and 8 weeks after the study in Group E-30 revealed that among the AAQol physical symptoms, “cold skin” was improved (p=0.026) and “blurred vision” was worsened (p=0.026) at 8 weeks after the study (Table 3). The additional symptom “menstruation-related troubles” also improved (p=0.038). With regard to mental symptoms, none of these improved whereas “inability to solve problems” worsened (p=0.046). For skin symptoms, improvement was noted in “make-up runs easily” (p=0.011) and “desiccated and gritty skin” (p=0.005), while “dull, fragile nails” was worsened (p=0.038). On comparison of the E-30 and control groups, the following changes in symptoms between baseline and 8 weeks differed, namely the physical symptoms “lethargy” (p=0.018), “skin problems” (p=0.003), and “menstruation-related troubles” (p=0.006); mental symptom “irritability” (p=0.031); and skin symptoms “make-up runs easily” (p=0.002), “course skin” (p=0.012), “desiccated and gritty skin” (p=0.003), and “thinning eyebrows” (p=0.011). Group E-30 demonstrated the favorable effects of the study product in all changes. The relationship between the number of study tablets prescribed and the change from baseline for each symptom at 8 weeks after the start of the study was evaluated to determine the presence of dose-dependence. Dose-dependent changes were noted for “skin problems” (p=– 0.50, p<0.01), “menstruation-related troubles” (p<0.05), “inability to solve problems” (p=0.36, p<0.05), “make-up runs easily” (p=0.54, p<0.01), “course skin” (p=– 0.45, p<0.05), “desiccated and gritty skin” (p=– 0.58, p<0.01), “skin sagging or swollen” (p=– 0.38, p<0.05), “no tone or complexion” (p=– 0.36, p<0.05) and “thinning eyebrows” (p=– 0.43, p<0.05). Changes were favorable for all symptoms excluding “inability to solve problems.”

Skin Analysis Measurement with SKI (using two-sided mean values) in Group E-30 revealed the following improvements: increased moisture content (+15.4%, p=0.010), reduced erythema (– 18.3%, p<0.001), and increased elasticity (+13.3%, p=0.003) (Table 4). Melanin significantly increased (+14.2%, p=0.031) in Group E-30 as was seen in the control. Inter-group analysis with the control group showed no significant differences in any of these parameters. Measurement with PSI in Group E-30 revealed improvements at 8 weeks after the start of the study in total moisture content (+14.5%, p=0.003), hydration (T zone) (+13.7%, p=0.003), hydration (U zone) (+18.2%, p=0.020), and pores (– 32.7%, p=0.022) (Table 5). Inter-group comparison demonstrated that among these parameters, total moisture content (p=0.015) and hydration (T zone) (p=0.016) showed more favorable effects in Group E-30 than in the control group. For “hydration (T zone),” the change from baseline noted at 8 weeks after the start of the study was dose-dependent (p=0.35, p<0.05) (Fig.1). Skin color measurement (using two-sided mean values) demonstrated improvements at 8 weeks in hemoglobin index (– 9.5%, p=0.016), lightness (L*) (+0.7%, p=0.045), and redness (a*) (– 8.3%, p=0.013) (Table 6). Inter-group analysis showed no significant difference between Group E-30 and the control group. With regard to lightness, the change from baseline noted at 8 weeks after the start of the study was dose-dependent (p=0.36, p<0.05) (Fig.2). Determination of skin elasticity with the Cutometer (using two-sided mean values) revealed that R0, which decreases as skin

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Data were obtained from the website of Japan Meteorological Agency in 2009 23).*UV amount: daily amount of ultraviolet. Data are expresse as a monthly average.

Table 2 Climate information during the observation term

February March April May

0 4 weeks 8 weeks

Average temperature

minimun

maximum

Avarage humidity

Duration of sunshine

UV amount*

Erythemal UV

UV-B

°C°C°C%

hour

kJ/m2

kJ/m2

7.8

11.5

4.4

50.0

131.2

±±

0.13

0.93

1.08

8.24

10.0

13.7

6.3

48.0

162.9

±±

0.13

1.00

1.54

11.75

15.7

20.2

11.9

54.0

226.7

±±

0.19

1.47

2.46

18.86

20.1

23.6

16.9

64.0

154.6

±±

0.18

1.40

2.60

19.81

Effects of Dried Brewer’s Yeast on Skin and QOL

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Table 3 Anti-Aging QOL Common Questionnaire and skin symptoms

Physical symptoms

Blurred vision

Lethargy

Skin problems

Cold skin

Menstruation-related troubles

Before(0w) vs. control8 weeks after

Group E-30

Mental symptoms

Irritability

Inability to solve problems

Group E-30 : n=11, Control group : n=11.Mean±SD.

1.55

1.82

2.73

3.00

2.55

0.93

0.87

0.90

1.61

1.44

±±±±±

2.18

1.73

2.09

2.36

2.18

1.08

1.19

0.94

1.36

1.33

±±±±±

p value

0.0260.724

0.089

0.0260.038

Before(0w) 8 weeks after

Control group

2.36

2.18

2.36

3.09

2.18

0.92

1.17

0.92

1.22

1.25

±±±±±

2.55

2.73

3.27

2.27

2.45

0.93

0.90

1.10

1.10

1.37

±±±±±

p value

0.553

0.0250.0160.0010.082

0.221

0.0180.0030.357

0.006

2.00

1.55

0.77

0.93±±

1.64

2.18

0.67

0.75±±

0.104

0.0462.18

2.27

1.17

1.19±±

2.45

2.36

1.13

1.12±±

0.391

0.588

0.0310.054

Skin symptoms

Noticeable pores

Noticeable blackheads in pores

Concerned about extension of pores

Dry skin

Concerned about dull skin

Frequent pimples

Itchy skin

Concerned about spots or

Make-up runs easily

Poor complexion

Oily face

Sticky or dirty skin

Coarse skin

Desiccated and gritty skin

Slackened skin

Not elastic, not glossy

Concerned about crows feet

Concerned about rough skin

Rough dry skin during

Bags under eyes

Corner of eyes sagging

Corners of mouth sagging

Thinning eyebrows

Fat chin

Thinning hair

Slow growing nails

Dull, fragile nails

3.91

3.36

3.91

4.36

3.36

2.82

2.09

3.91

3.55

2.18

2.36

2.00

2.73

3.36

4.27

4.18

3.09

3.45

2.91

1.91

3.09

3.18

1.73

3.00

1.91

1.36

2.18

1.04

1.36

1.38

0.81

1.21

1.40

1.58

1.30

1.13

1.08

1.21

0.77

1.10

0.81

0.79

0.98

1.38

1.13

1.58

0.83

1.45

1.47

1.19

1.34

0.83

0.50

1.40

±±±±±±±±±±±±±±±±±±±±±±±±±±±

3.36

3.00

3.55

4.09

3.45

2.82

1.73

3.91

2.73

2.36

1.91

1.91

2.00

2.55

3.64

3.27

3.00

3.00

3.27

1.73

3.18

3.09

1.45

2.82

2.00

1.64

2.55

1.21

1.26

1.44

0.70

1.37

1.33

0.79

1.04

1.19

1.12

1.22

1.14

0.63

0.69

1.12

1.27

1.10

1.34

1.27

0.65

1.40

1.30

0.69

1.40

1.00

0.81

1.63

±±±±±±±±±±±±±±±±±±±±±±±±±±±

0.052

0.104

0.104

0.493

0.676

1.000

0.420

1.000

0.0110.441

0.176

0.756

0.070

0.0050.132

0.064

0.676

0.360

0.341

0.506

0.756

0.724

0.192

0.659

0.588

0.277

0.038

3.36

3.27

3.36

3.36

3.09

3.27

2.00

3.45

2.27

2.45

2.36

2.09

2.18

2.18

3.00

3.09

2.73

2.91

3.00

2.36

2.91

3.00

1.45

2.73

2.64

2.00

2.36

1.12

0.90

1.21

0.81

0.94

1.49

0.77

0.82

0.90

0.93

1.43

1.30

0.75

0.60

1.34

1.04

1.10

0.94

1.26

0.92

1.14

0.89

0.52

1.42

1.29

0.63

1.43

±±±±±±±±±±±±±±±±±±±±±±±±±±±

3.36

3.27

3.18

3.55

3.00

3.18

2.45

3.64

2.73

2.55

2.45

2.55

2.73

3.09

3.36

3.09

2.82

3.45

3.55

2.73

3.00

3.18

1.91

3.00

2.55

1.91

2.82

0.81

0.79

0.98

0.82

1.18

1.40

0.93

0.81

0.90

0.93

1.21

1.04

1.27

1.14

0.92

1.04

1.08

1.13

1.21

0.90

1.00

0.87

0.83

1.18

1.13

0.70

1.33

±±±±±±±±±±±±±±±±±±±±±±±±±±±

1.000

1.000

0.341

0.588

0.676

0.588

0.242

0.441

0.096

0.756

0.724

0.138

0.111

0.064

0.307

1.000

0.779

0.216

0.052

0.221

0.676

0.441

0.053

0.192

0.724

0.756

0.242

0.081

0.164

0.330

0.377

0.506

0.534

0.164

0.611

0.0020.717

0.108

0.051

0.0120.0030.057

0.123

0.637

0.083

0.684

0.170

0.947

0.429

0.0110.302

0.550

0.338

0.290

Inter-group analysis

Table 4 Skin analysis: Measurement with SKI using mean values of the both sides

Sebum

Moisture

Melanin

Erythema

Elasticity


Group E-30

Group E-30 : n=11, Control group : n=11.Mean±SD, ND : not detected.

0.00

59.75

101.15

323.41

52.64

0.00

6.17

30.48

62.29

4.48

±±±±±

0.00

68.95

115.50

264.18

59.64

0.00

10.24

29.60

47.67

5.81

±±±±±

p value Before(0w) 8 weeks after p value

ND

0.0100.0310.0000.003

Control group

0.00

60.71

117.94

294.41

51.91

0.00

10.59

32.48

59.19

4.29

±±±±±

0.00

63.95

128.64

245.86

56.55

0.00

13.02

28.18

49.52

6.31

±±±±±

ND

0.424

0.0490.0000.025

ND

0.228

0.390

0.454

0.356


22

Table 6 Skin color measurement using mean values of the both sides

Index for the volume of melanin

Hemoglobin index

Lightness(L*)

Redness(a*)

Yellowness(b*)

vs. control

Group E-30


0.99

1.46

66.43

10.61

16.37

0.12

0.32

1.61

1.66

2.34

±±±±±

0.98

1.32

66.87

9.73

16.48

0.14

0.26

1.66

1.45

2.15

±±±±±

Before(0w) 8 weeks after p value

0.439

0.016

0.045

0.013

0.682

Control group

0.96

1.24

68.36

9.26

16.58

0.12

0.28

2.60

1.89

1.12

±±±±±

0.96

1.22

68.08

9.08

16.55

0.15

0.24

2.78

1.75

1.20

±±±±±

0.977

0.734

0.388

0.612

0.934


0.577

0.120

0.063

0.133

0.730


Table 7 Skin elasticity test and perspiration volume test using mean values of both sides

R0

R1

R2

R6

R7

vs. control

Group E-30


0.25

0.09

0.64

0.49

0.30

29.05

0.04

0.02

0.08

0.09

0.06

5.26

±±±±±

±

0.23

0.08

0.64

0.52

0.31

30.11

0.03

0.01

0.06

0.11

0.04

5.98

±±±±±

±


0.0060.0300.864

0.405

0.648

0.625

Control group

0.25

0.08

0.66

0.48

0.33

27.07

0.03

0.01

0.06

0.09

0.04

7.14

±±±±±

±

0.24

0.09

0.63

0.47

0.31

27.14

0.03

0.01

0.06

0.09

0.04

5.30

±±±±±

±

0.225

0.0400.0360.630

0.094

0.966

Before(0w)Skin elasticity index

Volume of perspiration

8 weeks after p value

0.084

0.0030.0470.313

0.068

0.710


Table 5 Skin analysis: Measurement with PSI using mean values of the both side

Oil

Oil

Total moisture content

Excess keratin

Hydration

Hydration

Pores

Wrinkles at the corner of the eye

T zone

U zone

T zone

U zone


Group E-30


0.42

0.11

47.64

12.88

35.18

27.00

16021

0.12

0.46

0.32

8.92

8.16

8.93

3.44

7577

0.02

±±±±±±±±

0.34

0.04

54.55

11.09

39.99

31.91

10785

0.11

0.32

0.09

8.18

8.52

7.76

6.41

3923

0.02

±±±±±±±±

p value Before(0w) 8 weeks after p value

0.365

0.292

0.0030.585

0.0030.0200.0220.510

Control group

0.43

0.09

46.91

6.19

31.03

26.36

18532

0.13

0.52

0.15

5.49

4.95

4.53

6.04

4223

0.03

±±±±±±±±

0.45

0.06

47.64

7.71

32.13

27.36

16770

0.12

0.58

0.08

6.14

4.78

6.31

5.57

3299

0.02

±±±±±±±±

0.866

0.452

0.621

0.326

0.227

0.649

0.063

0.082

0.523

0.251

0.0150.175

0.0160.175

0.101

0.474


Fig. 1. Dose-dependent change from baseline in moisture content (T zone) determined with PSI. * p < 0.05 vs control. Mean ± SEM, E-30 : n=11, E-9 : n=10, Control : n=11.

Fig. 2. Change from baseline in lightness (L*) determined by skin color analysis. Mean ± SEM, E-30 : n=11, E-9 : n=10, Control : n=11.


loses elasticity, decreased in Group E-30 (– 9.5%, p=0.006), although inter-group analysis showed no significant difference between Group E-30 and the control group (Table 7). R1, which decreases as the capability to return to the original state increases, decreased (– 8.6%, p=0.030), and more favorable effects were noted in Group E-30 than in the control group (inter-group analysis: p=0.003). R2, which represents the viscoelasticity of the skin and is considered the most reliable index, did not change significantly after 8 weeks (+0.4%, p=0.864), although more favorable effects were noted in Group E-30 than in the control group (inter-group analysis: p=0.047) (Fig.3). Dose-dependency was observed in the change from baseline for R1 (p=0.50, p<0.01) and from baseline for R5 (p=0.37, p<0.05). The change from baseline for R2 was significantly correlated to the change from baseline for R1 (p<0.01).

Evaluation of Adverse Events A 37-year-old woman in Group E-9 who used a face mask due to pollinosis for two days developed rashes on her jaw on the second day of treatment. These gradually increased and by day 13 had extended over the entire jaw. On day 15, treatment with the study product was discontinued, and the rash was treated with Locoid® (steroid), Azunol® (for topical use), Sato Salbe 10® (for topical use) and Allegra® (oral medicine). On the 18th day, the symptoms were resolved. This event was diagnosed as incidental contact dermatitis related to the face mask, and was rated as “unrelated” to the study product.

On the 44th day of treatment, a 33-year-old woman in Group E-30 went to an open-air concert and stayed for 2 hours in strong, direct exposure to the sun. On the 46th day, small rashes appeared on her face and neck, and on day 48 she stopped taking the study product. On the 51st day, the flare had extended over the entire face. She visited a dermatology clinic where photosensitivity was diagnosed, and treatment with a topical steroid was begun (Kindavate® 0.5 grams/day). On the 55th day, the symptom was relieved. She had experienced similar symptoms once in the past but the cause was unknown. The event was diagnosed as an incidental “photosensitivity” and determined “unrelated” to the study product.

23

Fig. 2. Dose-dependent change from baseline in skin elasticity indices R0, R1, R2 and R5 determined with Cutometer. * p < 0.05 vs control. Mean ± SEM, E-30 : n=11, E-9 : n=10, Control : n=11.

Discussion

The present study has provided interesting results regarding the effects of dried brewer’s yeast on the skin. Yeast first improved moisture content of the skin, and second improved elasticity. For moisture content, the significant improvement in the subjective symptom “desiccated and gritty skin” was supported by the improved moisture content of skin as determined by SKI and PSI. This finding appears highly reliable, since dose-dependence was confirmed in the 3 groups, i.e. the control group as well as Groups E-9 and E-30. For elasticity, measurements with a Cutometer and SKI confirmed the significant improvement in elasticity. Among Cutometer-related parameters, results showed that the most reliable, R2, was significantly different between Group E-30 and the control group at 8 weeks, which also supports the reliability of these findings. Very few studies have investigated the effect of yeast on skin, and no report could clearly explain the mechanism of improvement in moisture content and elasticity. Yeast extract from Saccharomycopsis was reported to inhibit, via gene expression of heme-oxigenase-1, the nitric oxide from macrophages, thus preventing the damage of epidermal cells 24). Antioxidant-enriched yeast may promote the ability of regeneration and protect the skin against doxorubicin toxicity 25). These results indicate that the supplementation of yeast as an anti-oxidant may prevent the damage of epidermal cells and enhance the ability of tissue regeneration. It is also possible to prevent the oxidative damage of collagen which plays a role to keep the skin elasticity. When the regeneration of the skin is activated, it also promotes the synthesis of collagen and ceramide which acts as a skin moisturizer. This may be a reason that the dried brewer’s yeast improved the skin elasticity and moisture amount in this study. In healthy adult men who used skincare cosmetics containing hydrolyzed yeast for 2 weeks, evaluation of effects on the skin by skin imaging revealed improvements in crows feet (wrinkles and stickiness at the corner of the eye) 26). This result is compatible with the present findings. Comparison of skin color before and after the study showed an improvement in Group E-30 in the volume of melanin and lightness. This finding suggests that some ingredients of dried brewer’s yeast, which include glutathione (γ-glutamine cysteinylglycine: GSH), biotin, nicotinic acid (niacin), vitamin B12 and essential amino acids such as tryptophan, are involved in the effects of yeast on the skin 27-30). Among these substances, GSH in particular decreases with aging 31) and is involved in the proliferation and differentiation of neurocytes 32). GSH deficiency induces neurodegeneration through oxidative stress 33), and GSH is decreased in patients with Alzheimer disease 34). More recently, its effect as a depigmenting agent has been reported 35). Biotin is essential to the maintenance of healthy skin and wound healing 36,37). Biotin deficiency induces skin diseases or alopecia 38,39). Tryptophan is involved in the synthesis of melanin, which has an antioxidant effect 40,41). In the skin, it has been reported that melanin protects the skin against ultraviolet rays 42,43) and reduces pigmentation so as to produce bright-looking skin 44). The state of the skin generally reflects the physical status such as gastrointestinal function. In the state of constipation, the amount of fermenting and degenerated products in intestines increases. These products shift into blood, and it becomes a cause to deteriolize the skin function 45). The brewers dried yeast is shown to improve the bowel movement 46,47). It is also reported that the dry yeast addition yogurt intake improves the intestinal environment of bacterial flora 48). These factors maybe play a role in contributing to the improvement of skin function, although “constipation” score was not significantly changed in this study.

Acknowledgment

This study was supported by Asahi Breweries Foundation (Sumida-ku, Tokyo) in 2009.

A serious side effect is not reported to the cellulose crystalline used as a placebo. It can explain the data change seen in the control group by the climatic difference. The skin test was done in March, April, and May. Meanwhile, the rise in the temperature and humidity, and the increase of durations of sunshine and the amount of ultraviolet rays were admitted (Table 2) 23). Especially, an increase of UV-B causes various troubles in the skin 49). In this study, the melanin amount in control showed significant increase (Table 4), and the skin elasticity seemed affected (Fig.3) although it was not significant. Also in the previous study performed in June, July and August 16), the increased UV sure caused the augmentation of pigmented lesions and melanin amount. The skin moisture amount in control seemed affected (Fig.1) in relation to the rise of humidity, however, it was not significant. On the other hand, in E-30 group, it is possible that effect is counterbalanced due to such a disadvantageous condition. Thus, a significant ameliorating effect might not have been in this study. The melanin amount admitted a significant increase due to the UV effect, however the lightness (L*) improved significantly by the skin color test. It is thought that the lightness improved to the extent that redness (a*) improves it, because this test is caught overall in the skin color tone. During the present study period, 2 subjects prematurely discontinued the study due to contact dermatitis in one subject in Group E-9 and photosensitivity in the second in Group E-30. In both subjects, these events were rated as “unrelated” to the study product since they were highly incidental. Throughout the study period, no serious adverse events were noted in the study subjects, including these discontinuations. Although skin symptom score “glossless and easily broken nails” has increased significantly in E-30 group, we did not judge it as a side effect. The reason is that the extent was negligible and the score rose to the same level as in control group. In conclusion, 8-week treatment of premenopausal women with dried brewer’s yeast at 7,125mg/day produced a significant improvement in the subjective symptoms “cold skin,” “menstruation-related troubles,” “make-up runs easily” and “desiccated and gritty skin.” Further, skin analysis demonstrated a significantly increased moisture content (about 15%), improved elasticity, and an improved hemoglobin index. These effects in improving moisture content and skin elasticity were dose-dependent. Findings suggestive of unfavorable effects were increased scores for the subjective symptoms of “blurred vision,” “inability to solve problems,” and “glossless and easily broken nails,” and an increased volume of melanin, as determined by skin analysis, although no serious adverse events were noted. These results indicate the possibility that treatment with the study product may be useful in improving both skin condition and QOL. Brewer’s yeast is a natural substance containing high levels of nutrients such as protein, carbohydrates, lipids, minerals, vitamins and dietary fiber, as shown in Table 1. In the future, brewer’s yeast is expected to be useful in a variety of fields, since it contains these ingredients in well-balanced combinations.

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