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BASIC/CLINICAL SCIENCE

Prospective, Randomized, Open-Label Trial Comparing the


Safety, Efficacy, and Tolerability of an Acne Treatment
Regimen with and without a Probiotic Supplement and
Minocycline in Subjects with Mild to Moderate Acne
Gordon W. Jung, Jennifer E. Tse, Isabella Guiha, and Jaggi Rao

Background: Systemic antibiotics are an effective treatment for acne vulgaris. However, intolerable side effects may invariably
occur.
Objective: To determine whether probiotics reduce the side effects imparted by systemic antibiotics while working
synergistically with the latter in treating inflammatory acne.
Methods: Forty-five 18- to 35-year-old females were randomly assigned to one of three arms in this prospective, open-label
study. Group A received probiotic supplementation, whereas group B received only minocycline. Group C was treated with both
probiotic and minocycline. Clinical and subjective assessments were completed at baseline and during the 2-, 4-, 8-, and 12-week
follow-up visits.
Results: All patients demonstrated a significant improvement in total lesion count 4 weeks after treatment initiation (p < .001),
with continued improvement seen with each subsequent follow-up visit (p < .01 ). At the 8- and 12-week follow-up visits, group C had
a significant decrease in total lesion count versus groups A (p < .001) and B (p < .01). Two patients (13%) from group B failed to
complete the study secondary to vaginal candidiasis.
Conclusion: Probiotics may be considered a therapeutic option or adjunct for acne vulgaris by providing a synergistic
antiinflammatory effect with systemic antibiotics while also reducing potential adverse events secondary to chronic antibiotic use.

Contexte: Les antibiotiques à action générale sont efficaces contre l'acné vulgaire, mais ils peuvent toujours produire des effets
indésirables intolérables.
Objectif: L'étude visait à déterminer si les probiotiques diminuaient les effets indésirables des antibiotiques à action générale,
tout en agissant en synergie avec ces derniers dans le traitement de l'acné inflammatoire.
Méthode: Quarante-cinq femmes, âgées de 18 à 35 ans, ont été dirigées au hasard vers l'un des trois groupes de traitement,
formés dans le cadre de cet essai prospectif, mené au su des parties; le groupe A a reçu un supplément probiotique; le groupe B, de la
minocycline seule; et le groupe C, le supplément probiotique et la minocycline. Il y a eu une évaluation clinique et subjective au
départ, puis à la 2e, 4e, 8e, et 12e semaine de suivi.
Résultats: Une diminution sensible du nombre total de lésions a été observée chez tous les sujets, 4 semaines après le début du
traitement (p < .001), diminution qui a été constatée à chacune des visites ultérieures de suivi (p < .01). Aux visites de la 8e et de la
12e semaine, une diminution importante du nombre total de lésions a été notée dans le groupe C comparativement aux groupes A (p
< .001) et B (p < .01). Deux patientes (13%) dans le groupe B n'ont pas terminé l'étude en raison d'une candidose vaginale.
Conclusions: Les probiotiques peuvent être envisagés comme formule thérapeutique ou appoint thérapeutique dans l'acné
vulgaire en produisant un effet anti-infiammatoire synergique avec celui des antibiotiques à action générale, en plus de diminuer les
effets indésirables possibles de l'emploi prolongé des antibiotiques.

From the Division of Dermatology and Cutaneous Sciences, Department Address reprint requests to: Jaggi Rao, MD, FRCPC, Division of
of Medicine, University of Alberta, Edmonton, AB; Shape MD, Dermatology and Cutaneous Sciences, Department of Medicine,
Edmonton, AB; Acne Clinics of Canada, Edmonton, AB; and University Dermatology Centre, 2-125 Clinical Sciences Bldg, Edmonton,
Dermatology and Cosmetic Laser Associates of La ¡olla. La Jolla, CA. ^ ^^^^ 2G3; e-mail: jrao@ualberta.ca.
The results of this study were presented at the 70th Annual Meeting of the ^ ^ ^ 10.2310/7750.2012.12026
American Academy of Dermatology, March 16-20, 2012, San Diego, CA. © 2013 Canadian Dermatology Association

DECKEI^
114 Canadian Dermatology Association I journal of Cutaneous Medicine and Surgery, Vol 17, No 2 (March/April), 2013: pp 114-122
Acne Treatment with Minocycline and/or Probiotics

CNE VULGARIS is one of the most common antiinflammatory mechanisms while imparting other health
A dermatologie diseases affecting Western societies and benefits when administered in adequate amounts.^ However,
typically presents during the adolescent period.' Although a review of the literature failed to identify studies assessing
not life-threatening, acne causes significant morbidity, both the effects of probiotics with antibiotics on acne vulgaris.
physically and psychologically. Specifically, severe acne has The purpose of this study was to determine whether
been associated with high levels of anxiety, major depres- probiotics reduced the side effects imparted by systemic
sion, social isolation, aggressive behavior, and suicidal antibiotics while working synergistically with the latter in
ideation.^ Furthermore, poorly controlled acne can lead to treating inflammatory acne.
irreversible disfigurement.
Acne treatment, consisting of topical, systemic, and
light and laser therapies, is individualized and dependent Methods
on the number and type of lesions a patient has. Oral
Subject Population
antibiotics have been used to treat a significant number of
acne patients with inflammatory disease, with the tetra- From May 2010 to April 2011, otherwise healthy,
cycline family being the most widely used.^ The tetra- nonpregnant female patients, 18 to 35 years of age with
cyclines alter the course of acne lesions via its bacteriostatic Fitzpatrick skin types I to III, were enrolled in this
action against Propionibacterium acnes by inhibiting prospective, randomized, open-label study. Only subjects
bacterial protein synthesis.* In addition, antibiotics have with mild to moderate acne vulgaris, with a score of 2 or 3
antiinflammatory properties through modulation of via the Global Acne Assessment Scale (Table 1) and 20 to
cytokine and reactive oxygen species production and 50 total lesions (with at least 10 inflammatory lesions),
reduction of leukocyte chemotaxis.^ Although effective, were included. The face was divided into five regions:
with a 22 to 91% and 23 to 75% reduction of forehead, nose, chin, right cheek, and left cheek.
inflammatory lesions after treatment with minocycline Patients were excluded from the trial if they had active
and doxycycline,^ respectively, side effects from such localized or generalized infections, a history of auto-
medications may occur, some of which may lead to immune disease, or a history of mental illness. Pregnant or
decreased compliance and/or discontinuation of the breastfeeding patients were also excluded from the study.
antibiotic. Such adverse effects include gastrointestinal Patients who smoked more than one pack per day, drank
disturbance, candidiasis, dizziness, lethargy, headaches, more than three alcoholic beverages per day, were
blue staining of the teeth in pédiatrie patients, and concurrently using isotretinoin, or changed their oral
photosensitivity and photo-onycholysis.^ contraceptive therapy within the past 3 months were not
The side effects of antibiotic treatment may be reduced included in the trial. Those with a history of probiotic use
via concomitant use of probiotics. Such live microorganisms (supplement and/or food enhanced) within the month
have been used for decades to alleviate abdominal symptoms prior to starting the study were excluded. Finally, subjects
via maintenance of commensal intestinal organisms and with excessive facial hair or scars, which could interfere

Table 1. Global Acne Assessment Scale

Grade Description
Normal, clear skin with no evidence of acne vulgaris
Skin is almost clear; rare noninflammatory lesions present, with rare noninflamed papules (papules must be resolving and
may be hyperpigmented, although not pink-red), requiring no further treatment in the investigator's opinion
Some noninflammatory lesions are present, with few inflammatory lesions (papules/pustules only; no nodulocystic lesions)
Noninflammatory lesions predominate, with multiple inflammatory lesions evident; several to many comedones and
papules/pustules, and there may or may not be one small nodulocystic lesion
Inflammatory lesions are more apparent; many comedones and papules/pustules; there may or may not be a few
nodulocystic lesions
Highly inflammatory lesions predominate: variable number of comedones, many papules/pustules and nodulocystic lesions
The Global Acne Assessment Scale used to categorize patients as mild, moderate, or severe acne vulgaris in the current study. To qualify for the study,
subjects were to have mild to moderate acne as determined by the investigative staff (defined as a score of 2 or 3) in addition to having between 20 and 50
total lesions with at least 10 inflammatory lesions.

' Canadian Dermatology Association I Journal of Cutaneous Mediane and Surgery, Vol 17, No 2 (March/April), 2013: pp 114-122 115
Jung et at

with clinical assessments, and those who had any facial study. Ethics approval was granted by the Health Research
cosmetic procedures completed within the 3 months prior Ethics Board (Biomédical Panel) of the University of
to study initiation were excluded. Alberta on April 9, 2010.

Study Design and Outcome Measures Data Analysis


Subjects were randomly assigned to one of three groups via a The efficacy of the three treatment regimens was
computer-generated schema. Group A received only probio- established by using a change in the average total, average
tic supplementation, whereas group B received only total inflamed, and average total noninfiamed lesion
minocycline. Group C was treated with both probiotic and counts along with a change in facial skin tolerability over
minocycline. Trenev Trio (professional)/Healthy Trinity the 12-week study period. Patients' subjective accounts
(retail) (Natren, Inc., Westlake Village, CA) was the probiotic with regard to their acne (quality of life) were also
product assessed in this study, which included a combination analyzed at baseline and at the 12-week follow-up visit. All
of Lactohadllus acidophilus (NAS super-strain, 5 billion statistical analyses were computed using the two-sample f-
colony-forming units [CFU)/capsule], Lactobacillus del- test assuming equal variance, with the level of significance
brueckii subspecies bulgaricus (LB-51 super-strain, 5 billion set at p < .05 (confidence level 95%) using the per
CFU/capsule), and Biftdobacterium biftdum (Malyoth super- protocol analysis strategy. Analysis included comparing
strain, 20 billion CFU/capsule) microenrobed in an oil matrix the effect of each treatment between two clinic visits within
within a two-piece hard gel capsule. each study group. The efficacy of the three treatment
Those randomized to a probiotic regimen (groups A regimens was also compared at each follow-up visit.
and C) were to take one probiotic capsule once in the
morning and once in the evening. Patients in the
minocycline arms (groups B and C) were advised to take Results
the antibiotic once after dinner. Those in group C were
Demographics and Adverse Events
instructed to take the probiotic at least 2 hours after their
minocycline dosage. All three arms of the study received a Forty-five otherwise healthy female patients with Fitzpatrick
standard topical acne medication (benzoyl peroxide 5%) skin types I to III, aged 18 to 35 years of age, were enrolled in
and a facial cleanser (Cetaphil Daily Facial Cleanser), the current study. Each arm of the study consisted of 15
which were applied once in the morning and once in the patients. Two subjects (13%) from the minocycline-only
evening. Each group was treated with the same regimen arm (group B) exited the study prematurely (one patient
that was initiated and was prohibited frotn using prior to week 4 and one prior to week 8) secondary to
additional acne treatments for the duration of the 12 intolerable vaginal candidiasis. No patients complained of
weeks they were enrolled in the study. any other adverse events.
Clinical evaluations and digital photographs were
performed at baseline and during follow-up visits 2, 4, 8,
Total Lesion Count
and 12 weeks from treatment initiation. Clinical assess-
ments included facial skin tolerability (degree of facial At baseline, patients in group A had an average total lesion
roughness, mottled pigmentation, sallowness, dullness, count of 30.5 (range 21^0). Similarly, at baseline, patients
inflammation, irritation, peeling, itching, burning/sting- in groups B and C had average total lesion counts of 30
ing, oiliness, scaling, xerosis, and erythema) on a 10-point (range 24-36) and 33 (range 24-41), respectively (Figure 1).
scale (0 = none; 1 to 3 = mild; 4 to 6 = moderate; 7 to 9 The percent decreases in total lesion count from
= severe) and acne lesion counts (total, noninflamed, and baseline for each group are presented in Table 2. By week
inflamed). All of the clinical procedures and evaluations 4, all three groups showed a significant improvement in
were completed by expert designates and investigators total lesion count from baseline (p < .001) with no
unaware of the patients' group assignments. As well, significant difference between groups [p > .05) (see
patients were asked to complete a self-assessment survey Figure 1 ). By week 8, all three groups showed a significant
during each visit addressing the eftect of acne on their improvement from week 4 (p = .001 for group A; p < .001
quality of life. for groups B and C). Group C also showed a significantly
All subjects were required to provide itiformed consent lower total lesion count versus both groups A (p < .001)
and photograph release consent prior to entering the and B (p = .006) (see Figure 1). By week 12, all groups

116 Canadian Dermatology Association I Journal of Cutaneous Medicine and Surgery, Vol 17, No 2 (March/April), 2013: pp 114-122
Acne Treatment with Minocycline and/or Probiotics

40 n

Baseline Week 2 Week 4 Week 8 Week 12


Figure 1. Change in total lesion counts (noninflamed and inflamed) over the 12-week study period. Blue, red, and green bars represent groups A,
B, and C, respectively. Error bars represent 95% confidence intervals.

showed a significant degree of improvement fi-om the noninflamed lesion counts from baseline (p < .001) with no
previous visit (p = .001 for group B; p < .001 for groups A significant difference between groups (p > .05) (see
and C). Again, group C showed a significantly reduced Figure 2). All arms also experienced a significant improve-
total lesion count than both groups A (p < .001) and B (p ment from week 4 to week 8 (p = .003 for group A; p < .001
< .001) at week 12 (see Figure 1). for groups B and C). By week 12, all groups again showed a
significant degree of improvement from the previous visit (p
= .02 for group B; p < .001 for groups A and C). In
Noninflamed Lesion Count
addition. Figure 2 illustrates that group C experienced a
At baseline, patients in the probiotic-only arm had a mean significantly lower total noninflamed lesion count than both
noninflamed lesion count of 19.8 (range 10-26). Groups B groups A (p = .03) and B (p = .001) at 12 weeks.
and C had average total noninflamed lesion counts of 19.2
(range 13-23) and 20.7 (range 15-28), respectively (Figure 2).
Inflamed Lesion Count
The percent decreases in noninflamed lesion count from
baseline for each group are presented in Table 2. By week 4, Group A had an average total inflamed lesion count of 10.7
all three groups showed a significant improvement in (range 5-15), whereas groups B and C had mean total

Table 2. Percent Decrease in Total, Noninflamed, and Inflamed Lesion Counts from Baseline

Decrease in Total Lesion Count from Decrease in Noninflamed Lesion Decrease in Inflamed Lesion Count from
Baseline (%) Count from Baseline (%) Baseline (%)

Week Group A Group B Group C Group A Group B Group C Group A Group B Group C

4 38 33 41 46 40 38 46* 40* 38
8 52 56 67 59 56 62 59 56 62
12 67 67 82 70 65 77 70 65 77

Group A = probiotic only; group B = minocycline only; group C = probiotic and minocycline.
*Not significant (p > .05).

/^
' Canadian Dermatology Association I Journal of Cutaneous Medicine and Surgery, Vol 17, No 2 (March/April), 2013: pp 114-122 117
Jung et al

Baseline Week 2 Week 4 Week 8 Week 12


Figure 2. Change in total noninflamed lesion counts over the 12-week study period. Blue, red, and green bars represent groups A, B, and C,
respectively. Error bars represent 95% confidence intervals.

inflamed lesion counts of 10.8 (range 2-15) and 12.3 skin roughness, mottled pigmentation, sallowness, dullness,
(range 6-19), respectively (Figure 3). inflammation, and irritation (p < .001) (Figure 4). A
The percent decreases in inflamed lesion count lrom significant improvement with regard to facial skin peeling,
baseline for each group are presented in Table 2. By week 4, itching, burning, oiliness, scaling, dryness, and erythema
only group C achieved a significant reduction in inflamed acne was also demonstrated in all three groups at the 12-week
lesions from baseline {p < .001) (see Figure 3), which was a follow-up visit (p < .001) (see Figure 4). Furthermore,
significant improvement versus group B {p = .04) (see Figure following 12 weeks of treatment with their appointed
3). By week 8, groups A and B also achieved significant regimens, compared to patients in groups A and B, subjects
improvement from baseline [p < .001), whereas group C in group C revealed a significant decrease in facial skin
continued to experience improvement from week 4 (p < dullness (mean difference 0.73 [p < .001] and 0.59 [p =
.001). At 8 weeks, group B demonstrated significanfly more .004], respectively), inflammation (mean difference 0.79 [p
improvement than group A (p = .04), whereas group C < .001] and 0.64 [p = .001], respectively), and erythema
showed significanfly more improvement compared to the (mean difterence 0.86 [p < .001] and 0.68 [p = .001],
other two arms (p < .001 versus group A; p = .006 versus respectively).
group B) (see Figure 3). By week 12, all groups again showed a
significant degree of improvement in inflamed lesion counts
Quality of Life Assessment
fi-om the previous visit (p = .001 for group A; p = .007 for
group B; p < .001 for group C). Furthermore, group B showed At the 12-week follow-up visit, patients from all three
significanfly more improvement versus group A (p = .02), groups were significantly happier with their appearance,
whereas group C showed significanfly more improvement more comfortable around others, less likely to avoid
compared to both groups A (p < .001) and B (p < .001). people, less hopeless about their skin, and less frustrated
about their acne (Table 3). Patients in groups A and B were
Skin Tolerabüity less discouraged about their acne at the 12-week follow-up
appointment, whereas those in groups A and C were less
Over the 12-week study period, patients from all three humiliated and those in groups B and C were less upset
groups established a significant improvement in their facial about their acne (see Table 3). Finafly, patients in the

Canadian Dermatology Association I Journal of Cutaneous Medicine and Surgery, Vol 17, No 2 (March/April), 2013: pp 114-122
Acne Treatment with Minocycline and/or Probiotics

16 -1

Baseline Week 2 Week 4 Week 8 Week 12


Figure 3. Change in total inflamed lesion counts over the 12-week study period. Blue, red, and green bars represent groups A, B, and C,
respectively. Error bars represent 95% confidence intervals.

combination minocycline-probiotic arm of the study were of the host's natural flora with antibiotic treatment can occur,
found to be more self-confident, more attractive to others, possibly resulting in intolerable gastrointestinal side effects
less self-conscious around others, less embarrassed, and and affecting patient compliance. Although no subjects
less ugly at the end of the treatment period. Such findings experienced gastrointestinal disturbances in the current
were not identified in the minocycline-only and probiotic- study, a meta-analysis of 19 studies found a reduction of
only arms (see Table 3). 52% (p < .001) in antibiotic-associated diarrhea with
probiotic use.^° Song and colleagues further found that
certain strains of Lactobacillus significantly maintained a
Discussion patient's bowel habits versus placebo when given during a
In recent decades, the characterization of specific probiotic course of antibiotics for a respiratory tract infection." Hence,
strains in preventing and treating infections and allergic antibiotic treatment of acne with concurrent administration
and inflammatory disorders has progressed significantly. of probiotics may reduce intolerable gastrointestinal adverse
Such beneficial health effects are believed to stem from the effects, improving patient compliance.
symbiotic relationship between the intestinal microbiota The vaginal microflora, consisting predominantly of
with the gut epithelium and mucosa. Specifically, the Lactobacillus species, may also be disrupted following
commensal flora has been found to extract nutrients from antibiotic use, leading to bacterial or fungal infections.
otherwise indigestible carbohydrates, compete with patho- Although the mechanism of gastrointestinal to vaginal
genic organisms for residence within the host's intestine, transmission is unclear, exogenous Lactobacillus species used
and modulate the deleterious effects of the mucosal innate on a consistent basis have been shown to colonize the female
and adaptive immune systems.^ More importantly, just as genital tract.^^'^^ Hence, it seems possible that speciflc
different antibiotics generate unique effects, different probiotics used in conjunction with antibiotics may reduce
probiotic strains provide specific health benefits, which the risk of disrupting a healthy vaginal ecosystem and
may include a role in acne therapeutics. populating the vaginal vault with pathogenic organisms.
Tetracyclines are effective and frequent therapeutic This was supported by the current study as 13% of subjects
options for inflammatory acne. Unfortunately, disturbance in the antibiotic-only arm developed vaginal candidiasis, an

• Canadian Dermatology Association I journal of Cutaneous Medicine and Surgery, Vol 17, No 2 (March/April), 2013: pp ¡14-122 119
Jung et al

Figure 3) and had an improved overall quality of life (see


Table 3). Such improvement may be secondary to the
antiinflammatory actions of both antibiotics and probio-
tics as the innate and adaptive immune systems have been
linked to acne pathogenesis. Upregulation of proinflam-
matory cytokines, including tumor necrosis factor a (TNF-
a), interleukin (IL)-lß, and IL-8, from sebocytes, kerati-
nocytes, and leukocytes, has led to the development of
acne lesions via activation of Toll-like receptors and GD14
by P. acnes and lipopolysaccharides.'^ Such inflammatory
results have been demonstrated to stem from activation of
the nuclear factor KB (NF-KB) and mitogen-associated
protein kinase (MAPK) pathways.'^ Furthermore, P. acnes
also triggers the adaptive immune system, with involve-
ment of T-helper 1 (Thl) cells and humoral immunity.'^'^^
Kwon and colleagues revealed a potential mechanism
in which probiotics can modulate inflammation. The
combination of five probiotic strains, which included
L. acidophilus and B. hiftdum, led to the generation of
regulatory dendritic cells and GD4'^ Foxp3^ T cells.^°
Abundance of such regulatory cells resulted in B and T
helper cell hyporesponsiveness without apoptosis, along
with suppression of cytokine production.^" Likewise, the
Figure 4. Baseline and week 12 follow-up photographs. Baseline
photographs of patients prior to randomization to the probiotic-only deleterious effects of TNF-a and interferon-y on the
(A), minocycline-only (B), or probiotic and minocycline combination intestinal epithelium were prevented by probiotics, a
(C) arms are shown. The photographs at the week 12 follow-up visit finding that may be helpful for other inflammatory
are also shown for patients completing the probiotic-only (D),
minocycline-only (E), and probiotic and minocycline combination conditions.^^ Tien and colleagues further supported the
(F) arms of the study. antiinflammatory potential of probiotics via its inhibitory
action on the NF-KB pathway.^^ Although preliminary, the
adverse event not experienced in the probiotic-only or the promising role of probiotics as immunomodulatory or
probiotic-minocycline groups. Although such findings are antiinflammatory agents definitely underscores their
contradictory to a study completed by Pirotta and possible role in acne therapeutics in a solo or synergistic
colleagues,'* several studies do reveal positive results with manner with antibiotics.
regard to the effect of different probiotic strains on recurrent Several limitations can be identified in the current study.
vulvovaginal candidiasis.^^''^ Furthermore, as it may require A small study population derived ftom a single community
time for exogenous probiotics to populate the vaginal practice and involving only fair-skinned female subjects
vault,^^ probiotic use prior to and during antibiotic prevents extrapolation of the current results to a broader
treatment may prove more effective in suppressing the scale. However, this preliminary study with novel findings
growth of harmful microorganisms in the internal female for acne treatment paves the way for future multicenter
genitalia versus starting these two forms of treatment at the studies in this field that involve a larger and more general
same time. Thus, future large-scale, multicentered studies patient population. Also, although the quality of life
are necessary to clarify probiotics' role in preventing questionnaire was not validated, it was based on what was
antibiotic-associated vaginal candidiasis. thought to be the most important and practical issues for
Not only can probiotics reduce the adverse events addressing the subjective feelings of patients with acne.
associated with antibiotic treatment, but probiotics may Furthermore, this study focused only on the Trenev Trio
also provide a synergistic effect with the latter in treating (professional)/Healthy Trinity (retail) probiotic combina-
acne vulgaris. Patients in the combined minocycline- tion; hence, extension of the current study results may not
probiotic arm of the current study experienced greater pertain to other probiotic strains. Of course, future studies
improvement in their acne compared to subjects using should evaluate and compare the efficacy of different
only one of these products (see Figure 1, Figure 2, and probiotic strains or combinations for acne vulgaris.

'120 Canadian Dermatology Association I Journal of Cutaneous Medicine and Surgery, Vol 17, No 2 (March/April), 2013: pp 114-122
Acne Treatment with Minocycline and/or Prohiotics

Table 3. Subject Quality of Life Questionnaire

Mean Difference of Patient Quality of Life Responses from Baseline to the 12-Week Follow-up Visit*

Group A Group B Group C

With respect to your acne, do you feel Mean Difference* p Value Mean Difference* p Value Mean Difference* p Value
Unhappy with your appearance? 1.2 0.005 1.4 0.004 2.3 < .001
Uncomfortable around others? 0.9 0.029 0.7 0.041 1.5 < .001
Angry? 0.2 NS 0.4 NS 0.5 NS
Less self-confident? 0.5 NS 0.8 NS 1.4 .002
Self-conscious around others? 0.3 NS 0.7 NS 1.4 < .001
Uneasy? -0.1 NS 0.1 NS 0.4 NS
Discouraged? 1.8 < .001 2.2 < .001 3.3 NS
Like you want to avoid people? 1.9 < .001 2.5 < .001 2.9 < .001
Sad or down? -0.4 NS 0.3 NS 0.3 NS
Humiliated? 1.0 .005 1.1 NS 2.4 < .001
Embarrassed? -0.1 NS 0.1 NS 0.5 .024
Upset? 0.5 NS 0.6 .031 1.2 < .001
Hopeless about your skin? 1.9 < .001 2.2 < .001 3.3 < .001
Unattractive to others? 0.5 NS 0.9 NS 1.3 .008
Frustrated? 1.5 < .001 1.2 < .001 2.1 < .001
Ugly? 0.5 NS 0.9 NS 1.5 .002
Uncomfortable? -0.1 NS -0.1 NS -0.1 NS
NS = not significant.
*Quality of life questions were based on a 7-point scale (1, 2 = not at all; 3, 4, 5 = sometimes; 6, 7 = extremely), with the mean difference calculated from
the baseline visit response to the 12-week follow-up visit response for each group.

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Acknowledgment food including powder milk with live lactic acid bacteria. Report of
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