Trial Outcomes & Findings for Stress & Anxiety Dampening Effects of a Probiotic Supplement Compared to Placebo in Healthy Subjects (NCT NCT03494725)

NCT ID: NCT03494725

Last Updated: 2021-02-25

Results Overview

Efficacy was defined as a lower increase in HR in response to the TSST following intervention with Lpc-37, compared to placebo.

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 120 participants
• Primary outcome timeframe: Continuous measurement starting 20 minutes before and ending 20 minutes after the TSST after 5 weeks of product intake. Mean values were calculated per group at seven-time windows before, during and after the TSST
• Results posted on: 2021-02-25

Participant Flow

Of 176 eligible participants, 120 met inclusion criteria and were enrolled in the study between April and October 2018.

Participant milestones

Measure	Lpc-37 Verum: Lacticaseibacillus paracasei Lpc-37 Ingredients: Lacticaseibacillus paracasei Lpc-37 at 1,75 x 10\^10 colony forming units (CFU) per day, microcrystalline cellulose, magnesium stearate, silicon dioxide Participants took one capsule of the Investigational Product (IP) every morning for 5 weeks, 30 minutes before breakfast or their first meal of the day, with a glass of plain (non-sparkling) water. Participants were stratified for both groups by gender and underlying chronic stress, as assessed using the Trier Inventory for Chronic Stress (TICS).	Placebo Placebo: capsule manufactured to mimic Lpc-37 capsule Ingredients: microcrystalline cellulose, magnesium stearate, silicon dioxide Participants took one capsule of the Investigational Product (IP) every morning for 5 weeks, 30 minutes before breakfast or their first meal of the day, with a glass of plain (non-sparkling) water. Participants were stratified for both groups by gender and underlying chronic stress, as assessed using the Trier Inventory for Chronic Stress (TICS).
Overall Study STARTED	60	60
Overall Study Intervention (Post 2 Weeks run-in)	59	59
Overall Study COMPLETED	59	58
Overall Study NOT COMPLETED	1	2

Reasons for withdrawal

Measure	Lpc-37 Verum: Lacticaseibacillus paracasei Lpc-37 Ingredients: Lacticaseibacillus paracasei Lpc-37 at 1,75 x 10\^10 colony forming units (CFU) per day, microcrystalline cellulose, magnesium stearate, silicon dioxide Participants took one capsule of the Investigational Product (IP) every morning for 5 weeks, 30 minutes before breakfast or their first meal of the day, with a glass of plain (non-sparkling) water. Participants were stratified for both groups by gender and underlying chronic stress, as assessed using the Trier Inventory for Chronic Stress (TICS).	Placebo Placebo: capsule manufactured to mimic Lpc-37 capsule Ingredients: microcrystalline cellulose, magnesium stearate, silicon dioxide Participants took one capsule of the Investigational Product (IP) every morning for 5 weeks, 30 minutes before breakfast or their first meal of the day, with a glass of plain (non-sparkling) water. Participants were stratified for both groups by gender and underlying chronic stress, as assessed using the Trier Inventory for Chronic Stress (TICS).
Overall Study Withdrawal by Subject	0	2
Overall Study Antibiotic use	1	0

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Measure	Lpc-37 n=60 Participants Verum: Lacticaseibacillus paracasei Lpc-37 (Lpc-37) Ingredients: Lacticaseibacillus paracasei Lpc-37 at 1,75 x 10\^10 colony forming units (CFU) per day, microcrystalline cellulose, magnesium stearate, silicon dioxide Participants took one capsule of the IP every morning for 5 weeks, 30 minutes before breakfast or their first meal of the day, with a glass of plain (non-sparkling) water. Participants were stratified for both groups by gender and underlying chronic stress, as assessed using the Trier Inventory for Chronic Stress (TICS).	Placebo n=60 Participants Placebo: capsule manufactured to mimic Lpc-37 capsule Ingredients: microcrystalline cellulose, magnesium stearate, silicon dioxide Participants took one capsule of the IP every morning for 5 weeks, 30 minutes before breakfast or their first meal of the day, with a glass of plain (non-sparkling) water. Participants were stratified for both groups by gender and underlying chronic stress, as assessed using the Trier Inventory for Chronic Stress (TICS).	Total n=120 Participants Total of all reporting groups
Age, Continuous	23.73 years STANDARD_DEVIATION 4.27 • n=60 Participants	23.25 years STANDARD_DEVIATION 4.20 • n=60 Participants	23.49 years STANDARD_DEVIATION 4.22 • n=120 Participants
Sex: Female, Male Female	30 Participants n=60 Participants	30 Participants n=60 Participants	60 Participants n=120 Participants
Sex: Female, Male Male	30 Participants n=60 Participants	30 Participants n=60 Participants	60 Participants n=120 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.
Region of Enrollment Germany	60 participants n=60 Participants	60 participants n=60 Participants	120 participants n=120 Participants
Weight	71.13 kg STANDARD_DEVIATION 11.05 • n=60 Participants	69.79 kg STANDARD_DEVIATION 12.15 • n=60 Participants	70.46 kg STANDARD_DEVIATION 11.58 • n=120 Participants
Height	175.58 cm STANDARD_DEVIATION 8.86 • n=60 Participants	173.58 cm STANDARD_DEVIATION 9.33 • n=60 Participants	174.58 cm STANDARD_DEVIATION 9.11 • n=120 Participants
Body Mass Index (BMI)	22.97 kg/m² STANDARD_DEVIATION 2.30 • n=60 Participants	23.02 kg/m² STANDARD_DEVIATION 2.67 • n=60 Participants	23.00 kg/m² STANDARD_DEVIATION 2.48 • n=120 Participants
Systolic blood pressure (BP)	120.75 mmHg STANDARD_DEVIATION 12.09 • n=60 Participants	120.72 mmHg STANDARD_DEVIATION 13.47 • n=60 Participants	120.73 mmHg STANDARD_DEVIATION 12.74 • n=120 Participants
Diastolic blood pressure (BP)	74.22 mmHg STANDARD_DEVIATION 7.25 • n=60 Participants	74.88 mmHg STANDARD_DEVIATION 8.53 • n=60 Participants	74.55 mmHg STANDARD_DEVIATION 7.88 • n=120 Participants
Heart rate	72.27 bpm STANDARD_DEVIATION 13.71 • n=60 Participants	71.03 bpm STANDARD_DEVIATION 12.43 • n=60 Participants	71.65 bpm STANDARD_DEVIATION 13.05 • n=120 Participants

PRIMARY outcome

Timeframe: Continuous measurement starting 20 minutes before and ending 20 minutes after the TSST after 5 weeks of product intake. Mean values were calculated per group at seven-time windows before, during and after the TSST

Population: PerProtocol population included all randomized participants that satisfied inclusion/exclusion criteria and had no major protocol deviations (total 113; Lpc-37 n=55; placebo n=58). For individual endpoints, participants were excluded if they showed deviations that were considered to possibly affect the endpoint in question (number analyzed varies).

Efficacy was defined as a lower increase in HR in response to the TSST following intervention with Lpc-37, compared to placebo.

Outcome measures

Measure	Lpc-37 n=55 Participants Verum: Lacticaseibacillus paracasei Lpc-37 Ingredients: Lacticaseibacillus paracasei Lpc-37 at 1,75 x 10\^10 colony forming units (CFU) per day, microcrystalline cellulose, magnesium stearate, silicon dioxide Participants took one capsule of the IP every morning for 5 weeks, 30 minutes before breakfast or their first meal of the day, with a glass of plain (non-sparkling) water. Participants were stratified for both groups by gender and underlying chronic stress, as assessed using the Trier Inventory for Chronic Stress (TICS).	Placebo n=57 Participants Placebo: capsule manufactured to mimic Lpc-37 capsule Ingredients: microcrystalline cellulose, magnesium stearate, silicon dioxide Participants took one capsule of the IP every morning for 5 weeks, 30 minutes before breakfast or their first meal of the day, with a glass of plain (non-sparkling) water. Participants were stratified by gender and stress level to both groups.
Change of the Heart Rate (HR) in Response to the Trier Social Stress Test (TSST) during TSST (Arithmetic)	102.77 bpm Standard Deviation 19.57	100.81 bpm Standard Deviation 17.20
Change of the Heart Rate (HR) in Response to the Trier Social Stress Test (TSST) Pre-TSST -20min	74.84 bpm Standard Deviation 10.20	74.34 bpm Standard Deviation 9.04
Change of the Heart Rate (HR) in Response to the Trier Social Stress Test (TSST) Pre-TSST -10min	88.15 bpm Standard Deviation 11.13	86.69 bpm Standard Deviation 10.74
Change of the Heart Rate (HR) in Response to the Trier Social Stress Test (TSST) Pre-TSST -3min	97.34 bpm Standard Deviation 17.15	97.62 bpm Standard Deviation 16.23
Change of the Heart Rate (HR) in Response to the Trier Social Stress Test (TSST) during TSST (Interview)	107.56 bpm Standard Deviation 21.56	105.66 bpm Standard Deviation 18.86
Change of the Heart Rate (HR) in Response to the Trier Social Stress Test (TSST) Post-TSST +10min	93.32 bpm Standard Deviation 14.08	90.81 bpm Standard Deviation 12.11
Change of the Heart Rate (HR) in Response to the Trier Social Stress Test (TSST) Post-TSST +20min	75.88 bpm Standard Deviation 11.11	74.97 bpm Standard Deviation 9.86

SECONDARY outcome

Timeframe: Before and after 5 weeks of study product intake.

Population: PerProtocol population included all randomized participants that satisfied inclusion/exclusion criteria and had no major protocol deviations (total 113; Lpc-37 n=55; placebo n=58). For individual endpoints, participants were excluded if they showed deviations that were considered to possibly affect the endpoint in question (number analyzed varies).

Efficacy of the intake of Lpc-37 on the reduction of State-Trait-Anxiety-Inventory (STAI)-state scores compared to placebo.

Measured with the german version of the State-Trait-Anxiety Inventory, scale anxiety as a temporary emotional state (STAI-X1). Answers are given on a four-point rating scale ranging from 1="not at all" to 4="very true". The score range is 20-80; Higher scores indicate more anxiety.

Outcome measures

Measure	Lpc-37 n=55 Participants Verum: Lacticaseibacillus paracasei Lpc-37 Ingredients: Lacticaseibacillus paracasei Lpc-37 at 1,75 x 10\^10 colony forming units (CFU) per day, microcrystalline cellulose, magnesium stearate, silicon dioxide Participants took one capsule of the IP every morning for 5 weeks, 30 minutes before breakfast or their first meal of the day, with a glass of plain (non-sparkling) water. Participants were stratified for both groups by gender and underlying chronic stress, as assessed using the Trier Inventory for Chronic Stress (TICS).	Placebo n=58 Participants Placebo: capsule manufactured to mimic Lpc-37 capsule Ingredients: microcrystalline cellulose, magnesium stearate, silicon dioxide Participants took one capsule of the IP every morning for 5 weeks, 30 minutes before breakfast or their first meal of the day, with a glass of plain (non-sparkling) water. Participants were stratified by gender and stress level to both groups.
Changes in Pre and Post Treatment STAI-state Scores Baseline	33.65 score Standard Deviation 6.80	34.33 score Standard Deviation 7.73
Changes in Pre and Post Treatment STAI-state Scores End of Study	35.18 score Standard Deviation 8.38	35.33 score Standard Deviation 8.37

SECONDARY outcome

Timeframe: Before and after 5 weeks of study product intake.

Population: PerProtocol population included all randomized participants that satisfied inclusion/exclusion criteria and had no major protocol deviations (total 113; Lpc-37 n=55; placebo n=58). For individual endpoints, participants were excluded if they showed deviations that were considered to possibly affect the endpoint in question (number analyzed varies).

Efficacy of the intake of Lpc-37 on the reduction of Perceived Stress Scale (PSS) scores compared to placebo.

Measured with the german version of the PSS as a psychological instrument for measuring stress perception. It assesses how unpredictable, uncontrollable and overloaded participants perceived their lives to have been within the last month. The PSS comprises 14 items that are answered on a five-point rating scale ranging from 0 = "never" to 4 = "very often". Individual scores on the PSS can range from 0 to 56 with higher scores indicating higher perceived stress.

Outcome measures

Measure	Lpc-37 n=55 Participants Verum: Lacticaseibacillus paracasei Lpc-37 Ingredients: Lacticaseibacillus paracasei Lpc-37 at 1,75 x 10\^10 colony forming units (CFU) per day, microcrystalline cellulose, magnesium stearate, silicon dioxide Participants took one capsule of the IP every morning for 5 weeks, 30 minutes before breakfast or their first meal of the day, with a glass of plain (non-sparkling) water. Participants were stratified for both groups by gender and underlying chronic stress, as assessed using the Trier Inventory for Chronic Stress (TICS).	Placebo n=57 Participants Placebo: capsule manufactured to mimic Lpc-37 capsule Ingredients: microcrystalline cellulose, magnesium stearate, silicon dioxide Participants took one capsule of the IP every morning for 5 weeks, 30 minutes before breakfast or their first meal of the day, with a glass of plain (non-sparkling) water. Participants were stratified by gender and stress level to both groups.
Changes in Pre and Post Treatment Perceived Stress Scale (PSS) Scores End of Study	20.49 score Standard Deviation 7.51	21.56 score Standard Deviation 8.16
Changes in Pre and Post Treatment Perceived Stress Scale (PSS) Scores Baseline	21.89 score Standard Deviation 7.90	20.72 score Standard Deviation 7.97

SECONDARY outcome

Timeframe: Before and after 5 weeks of study product intake.

Population: PerProtocol population included all randomized participants that satisfied inclusion/exclusion criteria and had no major protocol deviations (total 113; Lpc-37 n=55; placebo n=58). For individual endpoints, participants were excluded if they showed deviations that were considered to possibly affect the endpoint in question (number analyzed varies).

Efficacy of the intake of Lpc-37 on the reduction of Depression Anxiety Stress Scale (DASS) depression scores compared to placebo.

Measured with the german version of the DASS as a 42-item self report instrument designed to measure negative emotional states of depression, anxiety and stress during the past week. The DASS includes three scales (depression, anxiety and stress) of which each scale includes 14 items that are divided into subscales of 2-5 items of similar content.

Items are answered on a four point rating scale ranging from 0 = "not at all" to 3 = "very much". Scores of each scale are calculated by summing the scores for the relevant items.

The Depression scale assesses dysphoria, hopelessness, devaluation of life, self-deprecation, lack of interest/involvement, anhedonia, and inertia. The items are 3, 5, 10, 13, 16, 17, 21, 24, 26, 31, 34, 37, 38, 42 and individual scores can range from 0 to 42 with higher scores indicating greater severity of the symptoms.

Outcome measures

Measure	Lpc-37 n=55 Participants Verum: Lacticaseibacillus paracasei Lpc-37 Ingredients: Lacticaseibacillus paracasei Lpc-37 at 1,75 x 10\^10 colony forming units (CFU) per day, microcrystalline cellulose, magnesium stearate, silicon dioxide Participants took one capsule of the IP every morning for 5 weeks, 30 minutes before breakfast or their first meal of the day, with a glass of plain (non-sparkling) water. Participants were stratified for both groups by gender and underlying chronic stress, as assessed using the Trier Inventory for Chronic Stress (TICS).	Placebo n=58 Participants Placebo: capsule manufactured to mimic Lpc-37 capsule Ingredients: microcrystalline cellulose, magnesium stearate, silicon dioxide Participants took one capsule of the IP every morning for 5 weeks, 30 minutes before breakfast or their first meal of the day, with a glass of plain (non-sparkling) water. Participants were stratified by gender and stress level to both groups.
Changes in Pre and Post Treatment DASS Depression Scores Baseline	4.60 score Standard Deviation 4.94	5.21 score Standard Deviation 6.38
Changes in Pre and Post Treatment DASS Depression Scores End of Study	4.15 score Standard Deviation 5.52	5.10 score Standard Deviation 5.61

SECONDARY outcome

Timeframe: Before and after 5 weeks of study product intake.

Population: PerProtocol population included all randomized participants that satisfied inclusion/exclusion criteria and had no major protocol deviations (total 113; Lpc-37 n=55; placebo n=58). For individual endpoints, participants were excluded if they showed deviations that were considered to possibly affect the endpoint in question (number analyzed varies).

Efficacy of the intake of Lpc-37 on the reduction of Depression Anxiety Stress Scale (DASS) anxiety scores compared to placebo.

Measured with the german version of the DASS as a 42-item self report instrument designed to measure negative emotional states of depression, anxiety and stress during the past week. The DASS includes three scales (depression, anxiety and stress) of which each scale includes 14 items that are divided into subscales of 2-5 items of similar content.

Items are answered on a four point rating scale ranging from 0 = "not at all" to 3 = "very much". Scores of each scale are calculated by summing the scores for the relevant items.

The anxiety scale assesses autonomic arousal, skeletal muscle effects, situational anxiety, and subjective experience of anxious affect. The items are 2, 4, 7, 9, 15, 19, 20, 23, 25, 28, 30, 36, 40, 41 and individual scores can range from 0 to 42 with higher scores indicating greater severity of the symptoms.

Outcome measures

Measure	Lpc-37 n=55 Participants Verum: Lacticaseibacillus paracasei Lpc-37 Ingredients: Lacticaseibacillus paracasei Lpc-37 at 1,75 x 10\^10 colony forming units (CFU) per day, microcrystalline cellulose, magnesium stearate, silicon dioxide Participants took one capsule of the IP every morning for 5 weeks, 30 minutes before breakfast or their first meal of the day, with a glass of plain (non-sparkling) water. Participants were stratified for both groups by gender and underlying chronic stress, as assessed using the Trier Inventory for Chronic Stress (TICS).	Placebo n=58 Participants Placebo: capsule manufactured to mimic Lpc-37 capsule Ingredients: microcrystalline cellulose, magnesium stearate, silicon dioxide Participants took one capsule of the IP every morning for 5 weeks, 30 minutes before breakfast or their first meal of the day, with a glass of plain (non-sparkling) water. Participants were stratified by gender and stress level to both groups.
Changes in Pre and Post Treatment DASS Anxiety Scores Baseline	2.60 score Standard Deviation 3.35	3.07 score Standard Deviation 4.58
Changes in Pre and Post Treatment DASS Anxiety Scores End of Study	2.44 score Standard Deviation 3.59	3.45 score Standard Deviation 5.08

SECONDARY outcome

Timeframe: Before and after 5 weeks of study product intake.

Population: PerProtocol population included all randomized participants that satisfied inclusion/exclusion criteria and had no major protocol deviations (total 113; Lpc-37 n=55; placebo n=58). For individual endpoints, participants were excluded if they showed deviations that were considered to possibly affect the endpoint in question (number analyzed varies).

Efficacy of the intake of Lpc-37 on the reduction of Depression Anxiety Stress Scale (DASS) stress scores compared to placebo.

Measured with the german version of the DASS as a 42-item self report instrument designed to measure negative emotional states of depression, anxiety and stress during the past week. The DASS includes three scales (depression, anxiety and stress) of which each scale includes 14 items that are divided into subscales of 2-5 items of similar content.

Items are answered on a four point rating scale ranging from 0 = "not at all" to 3 = "very much". Scores of each scale are calculated by summing the scores for the relevant items.

The stress scale (items) is sensitive to levels of chronic non-specific arousal.The stress scale items are 1, 6, 8, 11, 12, 14, 18, 22, 27, 29, 32, 33, 35, 39 and individual scores can range from 0 to 42 with higher scores indicating greater severity of the symptoms.

Outcome measures

Measure	Lpc-37 n=55 Participants Verum: Lacticaseibacillus paracasei Lpc-37 Ingredients: Lacticaseibacillus paracasei Lpc-37 at 1,75 x 10\^10 colony forming units (CFU) per day, microcrystalline cellulose, magnesium stearate, silicon dioxide Participants took one capsule of the IP every morning for 5 weeks, 30 minutes before breakfast or their first meal of the day, with a glass of plain (non-sparkling) water. Participants were stratified for both groups by gender and underlying chronic stress, as assessed using the Trier Inventory for Chronic Stress (TICS).	Placebo n=58 Participants Placebo: capsule manufactured to mimic Lpc-37 capsule Ingredients: microcrystalline cellulose, magnesium stearate, silicon dioxide Participants took one capsule of the IP every morning for 5 weeks, 30 minutes before breakfast or their first meal of the day, with a glass of plain (non-sparkling) water. Participants were stratified by gender and stress level to both groups.
Changes in Pre and Post Treatment DASS Stress Scores End of Study	8.91 score Standard Deviation 7.14	10.09 score Standard Deviation 8.17
Changes in Pre and Post Treatment DASS Stress Scores Baseline	9.76 score Standard Deviation 7.92	9.41 score Standard Deviation 7.87

SECONDARY outcome

Timeframe: Before and after 5 weeks of study product intake.

Population: PerProtocol population included all randomized participants that satisfied inclusion/exclusion criteria and had no major protocol deviations (total 113; Lpc-37 n=55; placebo n=58). For individual endpoints, participants were excluded if they showed deviations that were considered to possibly affect the endpoint in question (number analyzed varies).

Efficacy of the intake of Lpc-37 on the reduction of Beck Anxiety Inventory (BAI) scores compared to placebo.

Measured with the german version of the Beck Anxiety Inventory as a self-rating scale designed to measure anxiety. It comprises 21 sentences describing feelings that can occur when being anxious. These sentences are rated on a four-point rating scale ranging from 0="not at all" to 3="severely", considering the last 7 days. The score range is 0-63; Higher scores indicate higher anxiety.

Outcome measures

Measure	Lpc-37 n=55 Participants Verum: Lacticaseibacillus paracasei Lpc-37 Ingredients: Lacticaseibacillus paracasei Lpc-37 at 1,75 x 10\^10 colony forming units (CFU) per day, microcrystalline cellulose, magnesium stearate, silicon dioxide Participants took one capsule of the IP every morning for 5 weeks, 30 minutes before breakfast or their first meal of the day, with a glass of plain (non-sparkling) water. Participants were stratified for both groups by gender and underlying chronic stress, as assessed using the Trier Inventory for Chronic Stress (TICS).	Placebo n=58 Participants Placebo: capsule manufactured to mimic Lpc-37 capsule Ingredients: microcrystalline cellulose, magnesium stearate, silicon dioxide Participants took one capsule of the IP every morning for 5 weeks, 30 minutes before breakfast or their first meal of the day, with a glass of plain (non-sparkling) water. Participants were stratified by gender and stress level to both groups.
Changes in Pre and Post Treatment BAI Scores Baseline	5.51 score Standard Deviation 4.46	5.85 score Standard Deviation 5.73
Changes in Pre and Post Treatment BAI Scores End of Study	4.75 score Standard Deviation 4.39	6.33 score Standard Deviation 7.26

SECONDARY outcome

Timeframe: Before and after 5 weeks of study product intake.

Population: PerProtocol population included all randomized participants that satisfied inclusion/exclusion criteria and had no major protocol deviations (total 113; Lpc-37 n=55; placebo n=58). For individual endpoints, participants were excluded if they showed deviations that were considered to possibly affect the endpoint in question (number analyzed varies).

Efficacy of the intake of Lpc-37 on the reduction of Visual Analog Scale (VAS) stress perception scores compared to placebo.

Measured with a german version of the Visual Analog Scale (VAS) as a 10cm bipolar scale ranging from "not at all" to "highly". The participant indicated his/her actual perception by placing a mark on a line. VAS scores were obtained by using a ruler and measuring the position of the participants's mark with millimeter precision. To control for possible variations due to printing, the total length of the line was also measured and percentage scores for each participant were computed. Percentage scores range from 0-100. Higher scores indicating higher perceived stress.

Outcome measures

Measure	Lpc-37 n=55 Participants Verum: Lacticaseibacillus paracasei Lpc-37 Ingredients: Lacticaseibacillus paracasei Lpc-37 at 1,75 x 10\^10 colony forming units (CFU) per day, microcrystalline cellulose, magnesium stearate, silicon dioxide Participants took one capsule of the IP every morning for 5 weeks, 30 minutes before breakfast or their first meal of the day, with a glass of plain (non-sparkling) water. Participants were stratified for both groups by gender and underlying chronic stress, as assessed using the Trier Inventory for Chronic Stress (TICS).	Placebo n=58 Participants Placebo: capsule manufactured to mimic Lpc-37 capsule Ingredients: microcrystalline cellulose, magnesium stearate, silicon dioxide Participants took one capsule of the IP every morning for 5 weeks, 30 minutes before breakfast or their first meal of the day, with a glass of plain (non-sparkling) water. Participants were stratified by gender and stress level to both groups.
Changes in Pre and Post Treatment VAS Stress Perception Scores Baseline	19.11 score Standard Deviation 22.97	19.34 score Standard Deviation 21.44
Changes in Pre and Post Treatment VAS Stress Perception Scores End of Study	23.32 score Standard Deviation 23.18	20.67 score Standard Deviation 21.63

SECONDARY outcome

Timeframe: Before and after 5 weeks of study product intake.

Population: PerProtocol population included all randomized participants that satisfied inclusion/exclusion criteria and had no major protocol deviations (total 113; Lpc-37 n=55; placebo n=58). For individual endpoints, participants were excluded if they showed deviations that were considered to possibly affect the endpoint in question (number analyzed varies).

Efficacy of the intake of Lpc-37 on the reduction of VAS anxiety scores compared to placebo.

Measured with a german version of the Visual Analog Scale (VAS) as a 10cm bipolar scale ranging from "not at all" to "highly". The participant indicated his/her actual perception by placing a mark on a line. VAS scores were obtained by using a ruler and measuring the position of the participants's mark with millimeter precision. To control for possible variations due to printing, the total length of the line was also measured and percentage scores for each participant were computed. Percentage scores range from 0-100. Higher scores indicating greater anxiety.

Outcome measures

Measure	Lpc-37 n=55 Participants Verum: Lacticaseibacillus paracasei Lpc-37 Ingredients: Lacticaseibacillus paracasei Lpc-37 at 1,75 x 10\^10 colony forming units (CFU) per day, microcrystalline cellulose, magnesium stearate, silicon dioxide Participants took one capsule of the IP every morning for 5 weeks, 30 minutes before breakfast or their first meal of the day, with a glass of plain (non-sparkling) water. Participants were stratified for both groups by gender and underlying chronic stress, as assessed using the Trier Inventory for Chronic Stress (TICS).	Placebo n=58 Participants Placebo: capsule manufactured to mimic Lpc-37 capsule Ingredients: microcrystalline cellulose, magnesium stearate, silicon dioxide Participants took one capsule of the IP every morning for 5 weeks, 30 minutes before breakfast or their first meal of the day, with a glass of plain (non-sparkling) water. Participants were stratified by gender and stress level to both groups.
Changes in Pre and Post Treatment VAS Anxiety Scores Baseline	7.29 score Standard Deviation 15.13	7.58 score Standard Deviation 14.05
Changes in Pre and Post Treatment VAS Anxiety Scores End of Study	9.26 score Standard Deviation 16.48	7.85 score Standard Deviation 13.40

SECONDARY outcome

Timeframe: Before and after 5 weeks of study product intake.

Population: PerProtocol population included all randomized participants that satisfied inclusion/exclusion criteria and had no major protocol deviations (total 113; Lpc-37 n=55; placebo n=58). For individual endpoints, participants were excluded if they showed deviations that were considered to possibly affect the endpoint in question (number analyzed varies).

Efficacy of the intake of Lpc-37 on the reduction of VAS insecurity scores compared to placebo.

Measured with a german version of the Visual Analog Scale (VAS) as a 10cm bipolar scale ranging from "not at all" to "highly". The participant indicated his/her actual perception by placing a mark on a line. VAS scores were obtained by using a ruler and measuring the position of the participants's mark with millimeter precision. To control for possible variations due to printing, the total length of the line was also measured and percentage scores for each participant were computed. Percentage scores range from 0-100. Higher scores indicating greater insecurity.

Outcome measures

Measure	Lpc-37 n=55 Participants Verum: Lacticaseibacillus paracasei Lpc-37 Ingredients: Lacticaseibacillus paracasei Lpc-37 at 1,75 x 10\^10 colony forming units (CFU) per day, microcrystalline cellulose, magnesium stearate, silicon dioxide Participants took one capsule of the IP every morning for 5 weeks, 30 minutes before breakfast or their first meal of the day, with a glass of plain (non-sparkling) water. Participants were stratified for both groups by gender and underlying chronic stress, as assessed using the Trier Inventory for Chronic Stress (TICS).	Placebo n=58 Participants Placebo: capsule manufactured to mimic Lpc-37 capsule Ingredients: microcrystalline cellulose, magnesium stearate, silicon dioxide Participants took one capsule of the IP every morning for 5 weeks, 30 minutes before breakfast or their first meal of the day, with a glass of plain (non-sparkling) water. Participants were stratified by gender and stress level to both groups.
Changes in Pre and Post Treatment VAS Insecurity Scores Baseline	13.58 score Standard Error 21.41	15.91 score Standard Error 19.60
Changes in Pre and Post Treatment VAS Insecurity Scores End of Study	16.44 score Standard Error 19.67	17.30 score Standard Error 20.15

SECONDARY outcome

Timeframe: Before and after 5 weeks of study product intake.

Population: PerProtocol population included all randomized participants that satisfied inclusion/exclusion criteria and had no major protocol deviations (total 113; Lpc-37 n=55; placebo n=58). For individual endpoints, participants were excluded if they showed deviations that were considered to possibly affect the endpoint in question (number analyzed varies).

Efficacy of the intake of Lpc-37 on the reduction of VAS exhaustion scores compared to placebo.

Measured with a german version of the Visual Analog Scale (VAS) as a 10cm bipolar scale ranging from "not at all" to "highly". The participant indicated his/her actual perception by placing a mark on a line. VAS scores were obtained by using a ruler and measuring the position of the participants's mark with millimeter precision. To control for possible variations due to printing, the total length of the line was also measured and percentage scores for each participant were computed. Percentage scores range from 0-100. Higher scores indicating greater exhaustion.

Outcome measures

Measure	Lpc-37 n=55 Participants Verum: Lacticaseibacillus paracasei Lpc-37 Ingredients: Lacticaseibacillus paracasei Lpc-37 at 1,75 x 10\^10 colony forming units (CFU) per day, microcrystalline cellulose, magnesium stearate, silicon dioxide Participants took one capsule of the IP every morning for 5 weeks, 30 minutes before breakfast or their first meal of the day, with a glass of plain (non-sparkling) water. Participants were stratified for both groups by gender and underlying chronic stress, as assessed using the Trier Inventory for Chronic Stress (TICS).	Placebo n=58 Participants Placebo: capsule manufactured to mimic Lpc-37 capsule Ingredients: microcrystalline cellulose, magnesium stearate, silicon dioxide Participants took one capsule of the IP every morning for 5 weeks, 30 minutes before breakfast or their first meal of the day, with a glass of plain (non-sparkling) water. Participants were stratified by gender and stress level to both groups.
Changes in Pre and Post Treatment VAS Exhaustion Scores Baseline	29.56 score Standard Deviation 27.63	23.19 score Standard Deviation 21.08
Changes in Pre and Post Treatment VAS Exhaustion Scores End of Study	24.66 score Standard Deviation 22.78	18.45 score Standard Deviation 21.31

SECONDARY outcome

Timeframe: Before and after 5 weeks of study product intake.

Population: PerProtocol population included all randomized participants that satisfied inclusion/exclusion criteria and had no major protocol deviations (total 113; Lpc-37 n=55; placebo n=58). For individual endpoints, participants were excluded if they showed deviations that were considered to possibly affect the endpoint in question (number analyzed varies).

Efficacy of the intake of Lpc-37 on the reduction of systolic blood pressure (BP).

Outcome measures

Measure	Lpc-37 n=55 Participants Verum: Lacticaseibacillus paracasei Lpc-37 Ingredients: Lacticaseibacillus paracasei Lpc-37 at 1,75 x 10\^10 colony forming units (CFU) per day, microcrystalline cellulose, magnesium stearate, silicon dioxide Participants took one capsule of the IP every morning for 5 weeks, 30 minutes before breakfast or their first meal of the day, with a glass of plain (non-sparkling) water. Participants were stratified for both groups by gender and underlying chronic stress, as assessed using the Trier Inventory for Chronic Stress (TICS).	Placebo n=58 Participants Placebo: capsule manufactured to mimic Lpc-37 capsule Ingredients: microcrystalline cellulose, magnesium stearate, silicon dioxide Participants took one capsule of the IP every morning for 5 weeks, 30 minutes before breakfast or their first meal of the day, with a glass of plain (non-sparkling) water. Participants were stratified by gender and stress level to both groups.
Changes in Pre and Post Treatment Systolic BP Baseline	119.60 mmHg Standard Deviation 14.21	119.66 mmHg Standard Deviation 13.82
Changes in Pre and Post Treatment Systolic BP End of Study	121.87 mmHg Standard Deviation 14.28	122.86 mmHg Standard Deviation 14.14

SECONDARY outcome

Timeframe: Before and after 5 weeks of study product intake.

Population: PerProtocol population included all randomized participants that satisfied inclusion/exclusion criteria and had no major protocol deviations (total 113; Lpc-37 n=55; placebo n=58). For individual endpoints, participants were excluded if they showed deviations that were considered to possibly affect the endpoint in question (number analyzed varies).

Efficacy of the intake of Lpc-37 on the reduction of diastolic BP.

Outcome measures

Measure	Lpc-37 n=55 Participants Verum: Lacticaseibacillus paracasei Lpc-37 Ingredients: Lacticaseibacillus paracasei Lpc-37 at 1,75 x 10\^10 colony forming units (CFU) per day, microcrystalline cellulose, magnesium stearate, silicon dioxide Participants took one capsule of the IP every morning for 5 weeks, 30 minutes before breakfast or their first meal of the day, with a glass of plain (non-sparkling) water. Participants were stratified for both groups by gender and underlying chronic stress, as assessed using the Trier Inventory for Chronic Stress (TICS).	Placebo n=58 Participants Placebo: capsule manufactured to mimic Lpc-37 capsule Ingredients: microcrystalline cellulose, magnesium stearate, silicon dioxide Participants took one capsule of the IP every morning for 5 weeks, 30 minutes before breakfast or their first meal of the day, with a glass of plain (non-sparkling) water. Participants were stratified by gender and stress level to both groups.
Changes in Pre and Post Treatment Diastolic BP Baseline	71.89 mmHg Standard Deviation 7.74	71.68 mmHg Standard Deviation 9.16
Changes in Pre and Post Treatment Diastolic BP End of Study	73.18 mmHg Standard Deviation 7.45	74.62 mmHg Standard Deviation 6.39

SECONDARY outcome

Timeframe: 10 minutes before the TSST and 1 minute after the TSST after 5 weeks of study product intake

Population: PerProtocol population included all randomized participants that satisfied inclusion/exclusion criteria and had no major protocol deviations (total 113; Lpc-37 n=55; placebo n=58). For individual endpoints, participants were excluded if they showed deviations that were considered to possibly affect the endpoint in question (number analyzed varies).

Efficacy of the intake of Lpc-37 on reduction of the increase of STAI-State scores in response to the TSST compared to placebo.

Measured with the german version of the State-Trait-Anxiety Inventory, scale anxiety as a temporary emotional state (STAI-X1). Answers are given on a four-point rating scale ranging from 1="not at all" to 4="very true". The score range is 20-80; Higher scores indicate more anxiety.

Outcome measures

Measure	Lpc-37 n=55 Participants Verum: Lacticaseibacillus paracasei Lpc-37 Ingredients: Lacticaseibacillus paracasei Lpc-37 at 1,75 x 10\^10 colony forming units (CFU) per day, microcrystalline cellulose, magnesium stearate, silicon dioxide Participants took one capsule of the IP every morning for 5 weeks, 30 minutes before breakfast or their first meal of the day, with a glass of plain (non-sparkling) water. Participants were stratified for both groups by gender and underlying chronic stress, as assessed using the Trier Inventory for Chronic Stress (TICS).	Placebo n=58 Participants Placebo: capsule manufactured to mimic Lpc-37 capsule Ingredients: microcrystalline cellulose, magnesium stearate, silicon dioxide Participants took one capsule of the IP every morning for 5 weeks, 30 minutes before breakfast or their first meal of the day, with a glass of plain (non-sparkling) water. Participants were stratified by gender and stress level to both groups.
Change of STAI-State Scores in Response to the TSST Post-TSST +1min	42.38 score Standard Deviation 10.91	43.60 score Standard Deviation 10.00
Change of STAI-State Scores in Response to the TSST Pre-TSST -10min	36.09 score Standard Deviation 8.45	36.83 score Standard Deviation 9.48

SECONDARY outcome

Timeframe: 3 minutes before the TSST and 1 minute after the TSST after 5 weeks of study product intake

Population: PerProtocol population included all randomized participants that satisfied inclusion/exclusion criteria and had no major protocol deviations (total 113; Lpc-37 n=55; placebo n=58). For individual endpoints, participants were excluded if they showed deviations that were considered to possibly affect the endpoint in question (number analyzed varies).

Efficacy of the intake of Lpc-37 on reduction of the increase of the systolic BP in response to the TSST compared to placebo.

Outcome measures

Measure	Lpc-37 n=55 Participants Verum: Lacticaseibacillus paracasei Lpc-37 Ingredients: Lacticaseibacillus paracasei Lpc-37 at 1,75 x 10\^10 colony forming units (CFU) per day, microcrystalline cellulose, magnesium stearate, silicon dioxide Participants took one capsule of the IP every morning for 5 weeks, 30 minutes before breakfast or their first meal of the day, with a glass of plain (non-sparkling) water. Participants were stratified for both groups by gender and underlying chronic stress, as assessed using the Trier Inventory for Chronic Stress (TICS).	Placebo n=58 Participants Placebo: capsule manufactured to mimic Lpc-37 capsule Ingredients: microcrystalline cellulose, magnesium stearate, silicon dioxide Participants took one capsule of the IP every morning for 5 weeks, 30 minutes before breakfast or their first meal of the day, with a glass of plain (non-sparkling) water. Participants were stratified by gender and stress level to both groups.
Change of Systolic BP in Response to the TSST Pre-TSST -3min	115.11 mmHg Standard Deviation 12.53	114.33 mmHg Standard Deviation 14.07
Change of Systolic BP in Response to the TSST Post-TSST +1min	127.47 mmHg Standard Deviation 13.67	129.19 mmHg Standard Deviation 14.33

SECONDARY outcome

Timeframe: 3 minutes before the TSST and 1 minute after the TSST after 5 weeks of study product intake

Population: PerProtocol population included all randomized participants that satisfied inclusion/exclusion criteria and had no major protocol deviations (total 113; Lpc-37 n=55; placebo n=58). For individual endpoints, participants were excluded if they showed deviations that were considered to possibly affect the endpoint in question (number analyzed varies).

Efficacy of the intake of Lpc-37 on reduction of the increase of the diastolic BP in response to the TSST compared to placebo.

Outcome measures

Measure	Lpc-37 n=55 Participants Verum: Lacticaseibacillus paracasei Lpc-37 Ingredients: Lacticaseibacillus paracasei Lpc-37 at 1,75 x 10\^10 colony forming units (CFU) per day, microcrystalline cellulose, magnesium stearate, silicon dioxide Participants took one capsule of the IP every morning for 5 weeks, 30 minutes before breakfast or their first meal of the day, with a glass of plain (non-sparkling) water. Participants were stratified for both groups by gender and underlying chronic stress, as assessed using the Trier Inventory for Chronic Stress (TICS).	Placebo n=58 Participants Placebo: capsule manufactured to mimic Lpc-37 capsule Ingredients: microcrystalline cellulose, magnesium stearate, silicon dioxide Participants took one capsule of the IP every morning for 5 weeks, 30 minutes before breakfast or their first meal of the day, with a glass of plain (non-sparkling) water. Participants were stratified by gender and stress level to both groups.
Change of Diastolic Blood Pressure (BP) in Response to the TSST Pre-TSST -3min	79.13 mmHg Standard Deviation 7.83	78.41 mmHg Standard Deviation 8.32
Change of Diastolic Blood Pressure (BP) in Response to the TSST Post-TSST +1min	90.38 mmHg Standard Deviation 7.17	88.36 mmHg Standard Deviation 9.72

SECONDARY outcome

Timeframe: 10 minutes before the TSST, during the TSST and 1 minute after the TSST after 5 weeks of study product intake

Population: PerProtocol population included all randomized participants that satisfied inclusion/exclusion criteria and had no major protocol deviations (total 113; Lpc-37 n=55; placebo n=58). For individual endpoints, participants were excluded if they showed deviations that were considered to possibly affect the endpoint in question (number analyzed varies).

Efficacy of the intake of Lpc-37 on reduction of the increase of VAS Stress perception scores in response to the TSST compared to placebo.

Measured with a german version of the Visual Analog Scale (VAS) as a 10cm bipolar scale ranging from "not at all" to "highly". The participant indicated his/her actual perception by placing a mark on a line. VAS scores were obtained by using a ruler and measuring the position of the participants's mark with millimeter precision. To control for possible variations due to printing, the total length of the line was also measured and percentage scores for each participant were computed. Percentage scores range from 0-100. Higher scores indicating higher perceived stress.

Outcome measures

Measure	Lpc-37 n=55 Participants Verum: Lacticaseibacillus paracasei Lpc-37 Ingredients: Lacticaseibacillus paracasei Lpc-37 at 1,75 x 10\^10 colony forming units (CFU) per day, microcrystalline cellulose, magnesium stearate, silicon dioxide Participants took one capsule of the IP every morning for 5 weeks, 30 minutes before breakfast or their first meal of the day, with a glass of plain (non-sparkling) water. Participants were stratified for both groups by gender and underlying chronic stress, as assessed using the Trier Inventory for Chronic Stress (TICS).	Placebo n=58 Participants Placebo: capsule manufactured to mimic Lpc-37 capsule Ingredients: microcrystalline cellulose, magnesium stearate, silicon dioxide Participants took one capsule of the IP every morning for 5 weeks, 30 minutes before breakfast or their first meal of the day, with a glass of plain (non-sparkling) water. Participants were stratified by gender and stress level to both groups.
Change of VAS Stress Perception Scores in Response to the TSST Pre-TSST -10min	19.89 score Standard Deviation 20.61	18.52 score Standard Deviation 21.73
Change of VAS Stress Perception Scores in Response to the TSST Interview TSST (during)	47.71 score Standard Deviation 27.08	51.51 score Standard Deviation 28.10
Change of VAS Stress Perception Scores in Response to the TSST Post-TSST +1min	31.72 score Standard Deviation 24.25	32.85 score Standard Deviation 23.66

SECONDARY outcome

Timeframe: 10 minutes before the TSST, during the TSST and 1 minute after the TSST after 5 weeks of study product intake

Population: PerProtocol population included all randomized participants that satisfied inclusion/exclusion criteria and had no major protocol deviations (total 113; Lpc-37 n=55; placebo n=58). For individual endpoints, participants were excluded if they showed deviations that were considered to possibly affect the endpoint in question (number analyzed varies).

Efficacy of the intake of Lpc-37 on reduction of the increase of VAS anxiety scores in response to the TSST compared to placebo.

Measured with a german version of the Visual Analog Scale (VAS) as a 10cm bipolar scale ranging from "not at all" to "highly". The participant indicated his/her actual perception by placing a mark on a line. VAS scores were obtained by using a ruler and measuring the position of the participants's mark with millimeter precision. To control for possible variations due to printing, the total length of the line was also measured and percentage scores for each participant were computed. Percentage scores range from 0-100. Higher scores indicating greater anxiety.

Outcome measures

Measure	Lpc-37 n=55 Participants Verum: Lacticaseibacillus paracasei Lpc-37 Ingredients: Lacticaseibacillus paracasei Lpc-37 at 1,75 x 10\^10 colony forming units (CFU) per day, microcrystalline cellulose, magnesium stearate, silicon dioxide Participants took one capsule of the IP every morning for 5 weeks, 30 minutes before breakfast or their first meal of the day, with a glass of plain (non-sparkling) water. Participants were stratified for both groups by gender and underlying chronic stress, as assessed using the Trier Inventory for Chronic Stress (TICS).	Placebo n=58 Participants Placebo: capsule manufactured to mimic Lpc-37 capsule Ingredients: microcrystalline cellulose, magnesium stearate, silicon dioxide Participants took one capsule of the IP every morning for 5 weeks, 30 minutes before breakfast or their first meal of the day, with a glass of plain (non-sparkling) water. Participants were stratified by gender and stress level to both groups.
Change of VAS Anxiety Scores in Response to the TSST Pre-TSST -10min	6.80 score Standard Deviation 10.95	8.50 score Standard Deviation 14.94
Change of VAS Anxiety Scores in Response to the TSST Interview TSST (during)	20.85 score Standard Deviation 23.61	22.47 score Standard Deviation 23.51
Change of VAS Anxiety Scores in Response to the TSST Post-TSST +1min	10.68 score Standard Deviation 15.19	11.74 score Standard Deviation 18.46

SECONDARY outcome

Timeframe: 10 minutes before the TSST, during the TSST and 1 minute after the TSST after 5 weeks of study product intake

Population: PerProtocol population included all randomized participants that satisfied inclusion/exclusion criteria and had no major protocol deviations (total 113; Lpc-37 n=55; placebo n=58). For individual endpoints, participants were excluded if they showed deviations that were considered to possibly affect the endpoint in question (number analyzed varies).

Efficacy of the intake of Lpc-37 on reduction of the increase of VAS insecurity scores in response to the TSST compared to placebo.

Measured with a german version of the Visual Analog Scale (VAS) as a 10cm bipolar scale ranging from "not at all" to "highly". The participant indicated his/her actual perception by placing a mark on a line. VAS scores were obtained by using a ruler and measuring the position of the participants's mark with millimeter precision. To control for possible variations due to printing, the total length of the line was also measured and percentage scores for each participant were computed. Percentage scores range from 0-100. Higher scores indicating greater insecurity.

Outcome measures

Measure	Lpc-37 n=55 Participants Verum: Lacticaseibacillus paracasei Lpc-37 Ingredients: Lacticaseibacillus paracasei Lpc-37 at 1,75 x 10\^10 colony forming units (CFU) per day, microcrystalline cellulose, magnesium stearate, silicon dioxide Participants took one capsule of the IP every morning for 5 weeks, 30 minutes before breakfast or their first meal of the day, with a glass of plain (non-sparkling) water. Participants were stratified for both groups by gender and underlying chronic stress, as assessed using the Trier Inventory for Chronic Stress (TICS).	Placebo n=58 Participants Placebo: capsule manufactured to mimic Lpc-37 capsule Ingredients: microcrystalline cellulose, magnesium stearate, silicon dioxide Participants took one capsule of the IP every morning for 5 weeks, 30 minutes before breakfast or their first meal of the day, with a glass of plain (non-sparkling) water. Participants were stratified by gender and stress level to both groups.
Change of VAS Insecurity Scores in Response to the TSST Pre-TSST -10min	14.47 score Standard Deviation 16.96	17.19 score Standard Deviation 21.37
Change of VAS Insecurity Scores in Response to the TSST Interview TSST (during)	45.08 score Standard Deviation 28.92	52.19 score Standard Deviation 27.16
Change of VAS Insecurity Scores in Response to the TSST Post-TSST +1min	23.92 score Standard Deviation 23.87	23.69 score Standard Deviation 23.58

SECONDARY outcome

Timeframe: 10 minutes before the TSST, during the TSST and 1 minute after the TSST after 5 weeks of study product intake

Population: PerProtocol population included all randomized participants that satisfied inclusion/exclusion criteria and had no major protocol deviations (total 113; Lpc-37 n=55; placebo n=58). For individual endpoints, participants were excluded if they showed deviations that were considered to possibly affect the endpoint in question (number analyzed varies).

Efficacy of the intake of Lpc-37 on reduction of the increase of VAS exhaustion scores in response to the TSST compared to placebo.

Measured with a german version of the Visual Analog Scale (VAS) as a 10cm bipolar scale ranging from "not at all" to "highly". The participant indicated his/her actual perception by placing a mark on a line. VAS scores were obtained by using a ruler and measuring the position of the participants's mark with millimeter precision. To control for possible variations due to printing, the total length of the line was also measured and percentage scores for each participant were computed. Percentage scores range from 0-100. Higher scores indicating greater exhaustion.

Outcome measures

Measure	Lpc-37 n=55 Participants Verum: Lacticaseibacillus paracasei Lpc-37 Ingredients: Lacticaseibacillus paracasei Lpc-37 at 1,75 x 10\^10 colony forming units (CFU) per day, microcrystalline cellulose, magnesium stearate, silicon dioxide Participants took one capsule of the IP every morning for 5 weeks, 30 minutes before breakfast or their first meal of the day, with a glass of plain (non-sparkling) water. Participants were stratified for both groups by gender and underlying chronic stress, as assessed using the Trier Inventory for Chronic Stress (TICS).	Placebo n=58 Participants Placebo: capsule manufactured to mimic Lpc-37 capsule Ingredients: microcrystalline cellulose, magnesium stearate, silicon dioxide Participants took one capsule of the IP every morning for 5 weeks, 30 minutes before breakfast or their first meal of the day, with a glass of plain (non-sparkling) water. Participants were stratified by gender and stress level to both groups.
Change of VAS Exhaustion Scores in Response to the TSST Pre-TSST -10min	21.18 score Standard Deviation 21.49	19.79 score Standard Deviation 21.88
Change of VAS Exhaustion Scores in Response to the TSST Interview TSST (during)	19.20 score Standard Deviation 21.11	21.30 score Standard Deviation 22.47
Change of VAS Exhaustion Scores in Response to the TSST Post-TSST +1min	22.12 score Standard Deviation 22.46	25.68 score Standard Deviation 26.07

SECONDARY outcome

Timeframe: 1 minute before the TSST and 1, 10, 20, 30 and 45 minutes after the TSST after 5 weeks of study product intake

Population: PerProtocol population included all randomized participants that satisfied inclusion/exclusion criteria and had no major protocol deviations (total 113; Lpc-37 n=55; placebo n=58). For individual endpoints, participants were excluded if they showed deviations that were considered to possibly affect the endpoint in question (number analyzed varies).

Efficacy of the intake of Lpc-37 on reduction of the increase of salivary cortisol in response to the TSST compared to placebo.

Outcome measures

Measure	Lpc-37 n=55 Participants Verum: Lacticaseibacillus paracasei Lpc-37 Ingredients: Lacticaseibacillus paracasei Lpc-37 at 1,75 x 10\^10 colony forming units (CFU) per day, microcrystalline cellulose, magnesium stearate, silicon dioxide Participants took one capsule of the IP every morning for 5 weeks, 30 minutes before breakfast or their first meal of the day, with a glass of plain (non-sparkling) water. Participants were stratified for both groups by gender and underlying chronic stress, as assessed using the Trier Inventory for Chronic Stress (TICS).	Placebo n=57 Participants Placebo: capsule manufactured to mimic Lpc-37 capsule Ingredients: microcrystalline cellulose, magnesium stearate, silicon dioxide Participants took one capsule of the IP every morning for 5 weeks, 30 minutes before breakfast or their first meal of the day, with a glass of plain (non-sparkling) water. Participants were stratified by gender and stress level to both groups.
Change of Salivary Cortisol in Response to the TSST Post-TSST +30min	8.04 nmol/L Standard Deviation 5.36	7.71 nmol/L Standard Deviation 5.06
Change of Salivary Cortisol in Response to the TSST Pre-TSST -2min	4.79 nmol/L Standard Deviation 2.62	4.82 nmol/L Standard Deviation 2.60
Change of Salivary Cortisol in Response to the TSST Post-TSST +1min	6.96 nmol/L Standard Deviation 3.73	6.85 nmol/L Standard Deviation 3.50
Change of Salivary Cortisol in Response to the TSST Post-TSST +10min	9.48 nmol/L Standard Deviation 5.75	8.97 nmol/L Standard Deviation 5.84
Change of Salivary Cortisol in Response to the TSST Post-TSST +20min	9.89 nmol/L Standard Deviation 6.51	9.21 nmol/L Standard Deviation 6.59
Change of Salivary Cortisol in Response to the TSST Post-TSST +45min	6.21 nmol/L Standard Deviation 3.17	6.16 nmol/L Standard Deviation 3.79

SECONDARY outcome

Timeframe: 1 minute before the TSST and 1, 10, 20, 30 and 45 minutes after the TSST after 5 weeks of study product intake

Population: PerProtocol population included all randomized participants that satisfied inclusion/exclusion criteria and had no major protocol deviations (total 113; Lpc-37 n=55; placebo n=58). For individual endpoints, participants were excluded if they showed deviations that were considered to possibly affect the endpoint in question (number analyzed varies).

Efficacy of the intake of Lpc-37 on reduction of the increase of salivary Alpha-Amylase (sAA) in response to the TSST compared to placebo.

Outcome measures

Measure	Lpc-37 n=55 Participants Verum: Lacticaseibacillus paracasei Lpc-37 Ingredients: Lacticaseibacillus paracasei Lpc-37 at 1,75 x 10\^10 colony forming units (CFU) per day, microcrystalline cellulose, magnesium stearate, silicon dioxide Participants took one capsule of the IP every morning for 5 weeks, 30 minutes before breakfast or their first meal of the day, with a glass of plain (non-sparkling) water. Participants were stratified for both groups by gender and underlying chronic stress, as assessed using the Trier Inventory for Chronic Stress (TICS).	Placebo n=57 Participants Placebo: capsule manufactured to mimic Lpc-37 capsule Ingredients: microcrystalline cellulose, magnesium stearate, silicon dioxide Participants took one capsule of the IP every morning for 5 weeks, 30 minutes before breakfast or their first meal of the day, with a glass of plain (non-sparkling) water. Participants were stratified by gender and stress level to both groups.
Change of sAA in Response to the TSST Post-TSST +20min	130.11 U/ml Standard Deviation 82.45	141.49 U/ml Standard Deviation 93.00
Change of sAA in Response to the TSST Pre-TSST -2min	154.04 U/ml Standard Deviation 98.17	161.67 U/ml Standard Deviation 110.89
Change of sAA in Response to the TSST Post-TSST +1min	246.29 U/ml Standard Deviation 153.62	270.55 U/ml Standard Deviation 174.85
Change of sAA in Response to the TSST Post-TSST +10min	146.53 U/ml Standard Deviation 86.80	158.85 U/ml Standard Deviation 91.21
Change of sAA in Response to the TSST Post-TSST +30min	125.19 U/ml Standard Deviation 79.67	138.48 U/ml Standard Deviation 90.31
Change of sAA in Response to the TSST Post-TSST +45min	141.13 U/ml Standard Deviation 92.94	148.15 U/ml Standard Deviation 105.60

SECONDARY outcome

Timeframe: Daily for 2 weeks before treatment intake and 5 weeks during treatment intake

Population: PerProtocol population included all randomized participants that satisfied inclusion/exclusion criteria and had no major protocol deviations (total 113; Lpc-37 n=55; placebo n=58). For individual endpoints, participants were excluded if they showed deviations that were considered to possibly affect the endpoint in question (number analyzed varies).

Efficacy of the intake of Lpc-37 on the increase of sleep duration over the course of the treatment.

Sleep duration was monitored through the wash-out phase (week 1 and 2) and the subsequent treatment phase (weeks 3-7). Efficacy is defined as an increase, or (in case of a general decrease) reduced decrease for the active treatment group as compared to the placebo group and operationalized as the interaction between time and treatment group. Time is coded as a continuous variable with one value for each day and participant. Summary measures for Sleep duration for the averaged ratings per participant and week

Outcome measures

Measure	Lpc-37 n=44 Participants Verum: Lacticaseibacillus paracasei Lpc-37 Ingredients: Lacticaseibacillus paracasei Lpc-37 at 1,75 x 10\^10 colony forming units (CFU) per day, microcrystalline cellulose, magnesium stearate, silicon dioxide Participants took one capsule of the IP every morning for 5 weeks, 30 minutes before breakfast or their first meal of the day, with a glass of plain (non-sparkling) water. Participants were stratified for both groups by gender and underlying chronic stress, as assessed using the Trier Inventory for Chronic Stress (TICS).	Placebo n=47 Participants Placebo: capsule manufactured to mimic Lpc-37 capsule Ingredients: microcrystalline cellulose, magnesium stearate, silicon dioxide Participants took one capsule of the IP every morning for 5 weeks, 30 minutes before breakfast or their first meal of the day, with a glass of plain (non-sparkling) water. Participants were stratified by gender and stress level to both groups.
Change of Sleep Duration Over the Course of the Treatment Week 7 (treatment)	445.60 min Standard Deviation 40.02	459.66 min Standard Deviation 39.71
Change of Sleep Duration Over the Course of the Treatment Week 1 (run-in)	447.27 min Standard Deviation 47.50	447.45 min Standard Deviation 38.76
Change of Sleep Duration Over the Course of the Treatment Week 2 (run-in)	444.01 min Standard Deviation 44.60	448.13 min Standard Deviation 41.62
Change of Sleep Duration Over the Course of the Treatment Week 3 (treatment)	449.45 min Standard Deviation 41.47	456.90 min Standard Deviation 37.08
Change of Sleep Duration Over the Course of the Treatment Week 4 (treatment)	450.62 min Standard Deviation 36.07	459.81 min Standard Deviation 39.44
Change of Sleep Duration Over the Course of the Treatment Week 5 (treatment)	454.50 min Standard Deviation 39.82	457.26 min Standard Deviation 42.04
Change of Sleep Duration Over the Course of the Treatment Week 6 (treatment)	450.88 min Standard Deviation 38.95	450.16 min Standard Deviation 42.04

SECONDARY outcome

Timeframe: Daily for 2 weeks before treatment intake and 5 weeks during treatment intake

Population: PerProtocol population included all randomized participants that satisfied inclusion/exclusion criteria and had no major protocol deviations (total 113; Lpc-37 n=55; placebo n=58). For individual endpoints, participants were excluded if they showed deviations that were considered to possibly affect the endpoint in question (number analyzed varies).

Efficacy of the intake of Lpc-37 on the increase of sleep related recovery scores over the course of the treatment.

Measured with a daily online diary. Sleep related recovery was rated by participants on an 11-point scale (0-10; "not at all" to "very") and monitored throughout the wash-out phase (Week 1 and 2) and the subsequent treatment phase (weeks 3-7). High scores indicate a high recovery.

Efficacy is defined as an increase, or (in case of a general decrease) reduced decrease for the active treatment group as compared to the placebo group and operationalized as the interaction between time and treatment group. Time is coded as a continuous variable with one value for each day and participant. Summary measures for sleep related recovery for the averaged ratings per participant and week.

Outcome measures

Measure	Lpc-37 n=44 Participants Verum: Lacticaseibacillus paracasei Lpc-37 Ingredients: Lacticaseibacillus paracasei Lpc-37 at 1,75 x 10\^10 colony forming units (CFU) per day, microcrystalline cellulose, magnesium stearate, silicon dioxide Participants took one capsule of the IP every morning for 5 weeks, 30 minutes before breakfast or their first meal of the day, with a glass of plain (non-sparkling) water. Participants were stratified for both groups by gender and underlying chronic stress, as assessed using the Trier Inventory for Chronic Stress (TICS).	Placebo n=47 Participants Placebo: capsule manufactured to mimic Lpc-37 capsule Ingredients: microcrystalline cellulose, magnesium stearate, silicon dioxide Participants took one capsule of the IP every morning for 5 weeks, 30 minutes before breakfast or their first meal of the day, with a glass of plain (non-sparkling) water. Participants were stratified by gender and stress level to both groups.
Change of Sleep Related Recovery Scores Over the Course of the Treatment Week 1 (run-in)	6.71 score Standard Deviation 1.34	6.91 score Standard Deviation 1.00
Change of Sleep Related Recovery Scores Over the Course of the Treatment Week 2 (run-in)	7.07 score Standard Deviation 1.28	7.15 score Standard Deviation 1.07
Change of Sleep Related Recovery Scores Over the Course of the Treatment Week 3 (treatment)	7.32 score Standard Deviation 1.11	7.27 score Standard Deviation 1.12
Change of Sleep Related Recovery Scores Over the Course of the Treatment Week 4 (treatment)	7.30 score Standard Deviation 1.30	7.29 score Standard Deviation 1.18
Change of Sleep Related Recovery Scores Over the Course of the Treatment Week 5 (treatment)	7.36 score Standard Deviation 1.22	7.36 score Standard Deviation 1.19
Change of Sleep Related Recovery Scores Over the Course of the Treatment Week 6 (treatment)	7.42 score Standard Deviation 1.19	7.10 score Standard Deviation 1.28
Change of Sleep Related Recovery Scores Over the Course of the Treatment Week 7 (treatment)	7.31 score Standard Deviation 1.25	7.28 score Standard Deviation 1.18

SECONDARY outcome

Timeframe: Daily for 2 weeks before treatment intake and 5 weeks during treatment intake

Population: PerProtocol population included all randomized participants that satisfied inclusion/exclusion criteria and had no major protocol deviations (total 113; Lpc-37 n=55; placebo n=58). For individual endpoints, participants were excluded if they showed deviations that were considered to possibly affect the endpoint in question (number analyzed varies and is listet for each endpoint).

Efficacy of the intake of Lpc-37 on the decrease of sleep disruptions over the course of the treatment measured with a daily online diary (Proportion (yes/total)).

Sleep disruptions were monitored through the wash-out phase and the subsequent treatment phase for each week. In the binary version, the value is either Yes or No for each day and each participant.

Efficacy is defined as a decrease, or (in case of a general increase) reduced increase for the active treatment group as compared to the placebo group and operationalized as the interaction between time and treatment group. Time is coded as a continuous variable with one value for each day and participant.

The proportion of participants with at least one sleep disruption by treatment group is given, treatment commenced after week 2. Data listed here reflect the proportion of participants who answered "Yes" (e.g. 0,477 * 44 = 20.99 participants answered with "Yes" in week 1 in the Lpc-37 group).

Outcome measures

Measure	Lpc-37 n=44 Participants Verum: Lacticaseibacillus paracasei Lpc-37 Ingredients: Lacticaseibacillus paracasei Lpc-37 at 1,75 x 10\^10 colony forming units (CFU) per day, microcrystalline cellulose, magnesium stearate, silicon dioxide Participants took one capsule of the IP every morning for 5 weeks, 30 minutes before breakfast or their first meal of the day, with a glass of plain (non-sparkling) water. Participants were stratified for both groups by gender and underlying chronic stress, as assessed using the Trier Inventory for Chronic Stress (TICS).	Placebo n=47 Participants Placebo: capsule manufactured to mimic Lpc-37 capsule Ingredients: microcrystalline cellulose, magnesium stearate, silicon dioxide Participants took one capsule of the IP every morning for 5 weeks, 30 minutes before breakfast or their first meal of the day, with a glass of plain (non-sparkling) water. Participants were stratified by gender and stress level to both groups.
Change of Reported Sleep Disruptions Over the Course of the Treatment by Week (Proportion Yes/Total) Week 2 (run-in)	0.435 Proportion of participants (yes/total)	0.426 Proportion of participants (yes/total)
Change of Reported Sleep Disruptions Over the Course of the Treatment by Week (Proportion Yes/Total) Week 1 (run-in)	0.477 Proportion of participants (yes/total)	0.465 Proportion of participants (yes/total)
Change of Reported Sleep Disruptions Over the Course of the Treatment by Week (Proportion Yes/Total) Week 3 (treatment)	0.354 Proportion of participants (yes/total)	0.418 Proportion of participants (yes/total)
Change of Reported Sleep Disruptions Over the Course of the Treatment by Week (Proportion Yes/Total) Week 4 (treatment)	0.367 Proportion of participants (yes/total)	0.310 Proportion of participants (yes/total)
Change of Reported Sleep Disruptions Over the Course of the Treatment by Week (Proportion Yes/Total) Week 5 (treatment)	0.306 Proportion of participants (yes/total)	0.292 Proportion of participants (yes/total)
Change of Reported Sleep Disruptions Over the Course of the Treatment by Week (Proportion Yes/Total) Week 6 (treatment)	0.279 Proportion of participants (yes/total)	0.331 Proportion of participants (yes/total)
Change of Reported Sleep Disruptions Over the Course of the Treatment by Week (Proportion Yes/Total) Week 7 (treatment)	0.290 Proportion of participants (yes/total)	0.389 Proportion of participants (yes/total)

SECONDARY outcome

Timeframe: Daily for 2 weeks before treatment intake and 5 weeks during treatment intake

Population: PerProtocol population included all randomized participants that satisfied inclusion/exclusion criteria and had no major protocol deviations (total 113; Lpc-37 n=55; placebo n=58). For individual endpoints, participants were excluded if they showed deviations that were considered to possibly affect the endpoint in question (number analyzed varies).

Efficacy of the intake of Lpc-37 on the decrease of reported number of sleep disruptions over the course of the treatment measured with a daily online diary (mean of week summary).

Sleep disruptions were monitored through the wash-out phase (Week 1 and 2) and the subsequent treatment phase (Weeks 3-7). In the count version, the value can be 0 or a natural number for each day and each participant. Efficacy is defined as a decrease, or (in case of a general increase) reduced increase for the active treatment group as compared to the placebo group and operationalized as the interaction between time and treatment group. Time is coded as a continuous variable with one value for each day and participant. Values reflect summary measures for sleep disruptions (count) for the summed counts per participant and week.

Outcome measures

Measure	Lpc-37 n=44 Participants Verum: Lacticaseibacillus paracasei Lpc-37 Ingredients: Lacticaseibacillus paracasei Lpc-37 at 1,75 x 10\^10 colony forming units (CFU) per day, microcrystalline cellulose, magnesium stearate, silicon dioxide Participants took one capsule of the IP every morning for 5 weeks, 30 minutes before breakfast or their first meal of the day, with a glass of plain (non-sparkling) water. Participants were stratified for both groups by gender and underlying chronic stress, as assessed using the Trier Inventory for Chronic Stress (TICS).	Placebo n=47 Participants Placebo: capsule manufactured to mimic Lpc-37 capsule Ingredients: microcrystalline cellulose, magnesium stearate, silicon dioxide Participants took one capsule of the IP every morning for 5 weeks, 30 minutes before breakfast or their first meal of the day, with a glass of plain (non-sparkling) water. Participants were stratified by gender and stress level to both groups.
Change of Reported Number of Sleep Disruptions Over the Course of the Treatment Week 2 (run-in)	5.50 sleep disruptions per participant & week Standard Deviation 4.62	5.49 sleep disruptions per participant & week Standard Deviation 4.82
Change of Reported Number of Sleep Disruptions Over the Course of the Treatment Week 1 (run-in)	7.30 sleep disruptions per participant & week Standard Deviation 6.87	6.09 sleep disruptions per participant & week Standard Deviation 4.96
Change of Reported Number of Sleep Disruptions Over the Course of the Treatment Week 3 (treatment)	4.89 sleep disruptions per participant & week Standard Deviation 5.11	5.11 sleep disruptions per participant & week Standard Deviation 4.89
Change of Reported Number of Sleep Disruptions Over the Course of the Treatment Week 4 (treatment)	5.43 sleep disruptions per participant & week Standard Deviation 9.20	4.30 sleep disruptions per participant & week Standard Deviation 6.05
Change of Reported Number of Sleep Disruptions Over the Course of the Treatment Week 5 (treatment)	3.52 sleep disruptions per participant & week Standard Deviation 3.48	3.53 sleep disruptions per participant & week Standard Deviation 3.80
Change of Reported Number of Sleep Disruptions Over the Course of the Treatment Week 6 (treatment)	3.80 sleep disruptions per participant & week Standard Deviation 7.40	4.02 sleep disruptions per participant & week Standard Deviation 4.68
Change of Reported Number of Sleep Disruptions Over the Course of the Treatment Week 7 (treatment)	4.66 sleep disruptions per participant & week Standard Deviation 6.37	5.83 sleep disruptions per participant & week Standard Deviation 6.23

SECONDARY outcome

Timeframe: Daily for 2 weeks before treatment intake and 5 weeks during treatment intake

Population: PerProtocol population included all randomized participants that satisfied inclusion/exclusion criteria and had no major protocol deviations (total 113; Lpc-37 n=55; placebo n=58). For individual endpoints, participants were excluded if they showed deviations that were considered to possibly affect the endpoint in question (number analyzed varies).

Efficacy of the intake of Lpc-37 on the increase of perceived health status scores over the course of the treatment.

Measured with a daily online diary. Health status was rated by participants on an 11-point scale (0-10; "not at all" to "very") and monitored through the wash-out phase (week 1 and 2) and the subsequent treatment phase (weeks 3-7). Higher scores indicate a high perceived health.Efficacy is defined as an increase, or (in case of a general decrease) reduced decrease for the active treatment group as compared to the placebo group and operationalized as the interaction between time and treatment group. Time is coded as a continuous variable with one value for each day and participant. Values reflect summary measures for perceived health status on a scale from 0 to 10 for the averaged ratings per participant and week.

Outcome measures

Measure	Lpc-37 n=44 Participants Verum: Lacticaseibacillus paracasei Lpc-37 Ingredients: Lacticaseibacillus paracasei Lpc-37 at 1,75 x 10\^10 colony forming units (CFU) per day, microcrystalline cellulose, magnesium stearate, silicon dioxide Participants took one capsule of the IP every morning for 5 weeks, 30 minutes before breakfast or their first meal of the day, with a glass of plain (non-sparkling) water. Participants were stratified for both groups by gender and underlying chronic stress, as assessed using the Trier Inventory for Chronic Stress (TICS).	Placebo n=47 Participants Placebo: capsule manufactured to mimic Lpc-37 capsule Ingredients: microcrystalline cellulose, magnesium stearate, silicon dioxide Participants took one capsule of the IP every morning for 5 weeks, 30 minutes before breakfast or their first meal of the day, with a glass of plain (non-sparkling) water. Participants were stratified by gender and stress level to both groups.
Change of Perceived Health Status Scores Over the Course of the Treatment Week 1 (run-in)	7.80 score Standard Deviation 1.31	7.86 score Standard Deviation 1.08
Change of Perceived Health Status Scores Over the Course of the Treatment Week 2 (run-in)	7.89 score Standard Deviation 1.15	7.92 score Standard Deviation 1.12
Change of Perceived Health Status Scores Over the Course of the Treatment Week 3 (treatment)	7.88 score Standard Deviation 1.20	7.92 score Standard Deviation 1.06
Change of Perceived Health Status Scores Over the Course of the Treatment Week 4 (treatment)	7.91 score Standard Deviation 1.18	8.01 score Standard Deviation 1.05
Change of Perceived Health Status Scores Over the Course of the Treatment Week 5 (treatment)	8.05 score Standard Deviation 1.22	7.92 score Standard Deviation 1.16
Change of Perceived Health Status Scores Over the Course of the Treatment Week 6 (treatment)	8.11 score Standard Deviation 1.20	7.73 score Standard Deviation 1.26
Change of Perceived Health Status Scores Over the Course of the Treatment Week 7 (treatment)	7.91 score Standard Deviation 1.15	7.75 score Standard Deviation 1.52

SECONDARY outcome

Timeframe: Daily for 2 weeks before treatment intake and 5 weeks during treatment intake

Population: PerProtocol population included all randomized participants that satisfied inclusion/exclusion criteria and had no major protocol deviations (total 113; Lpc-37 n=55; placebo n=58). For individual endpoints, participants were excluded if they showed deviations that were considered to possibly affect the endpoint in question (number analyzed varies).

Efficacy of the intake of Lpc-37 on the increase of mood scale scores over the course of the treatment

Measured with a daily online diary. Mood was rated by participants on an 11-point scale (0-10; "very bad" to "very well") and monitored through the washout phase (week 1 and 2) and the subsequent treatment phase (weeks 3-7). Higher scores indicate a better mood. Efficacy is defined as an increase, or (in case of a general decrease) reduced decrease for the active treatment group as compared to the placebo group and operationalized as the interaction between time and treatment group. Time is coded as a continuous variable with one average value for each week and participant. Values reflect summary measures for mood ratings on a scale from 0 to 10 for the averaged ratings per participant and week.

Outcome measures

Measure	Lpc-37 n=44 Participants Verum: Lacticaseibacillus paracasei Lpc-37 Ingredients: Lacticaseibacillus paracasei Lpc-37 at 1,75 x 10\^10 colony forming units (CFU) per day, microcrystalline cellulose, magnesium stearate, silicon dioxide Participants took one capsule of the IP every morning for 5 weeks, 30 minutes before breakfast or their first meal of the day, with a glass of plain (non-sparkling) water. Participants were stratified for both groups by gender and underlying chronic stress, as assessed using the Trier Inventory for Chronic Stress (TICS).	Placebo n=47 Participants Placebo: capsule manufactured to mimic Lpc-37 capsule Ingredients: microcrystalline cellulose, magnesium stearate, silicon dioxide Participants took one capsule of the IP every morning for 5 weeks, 30 minutes before breakfast or their first meal of the day, with a glass of plain (non-sparkling) water. Participants were stratified by gender and stress level to both groups.
Change of Mood Scale Scores Over the Course of the Treatment Week 1 (run-in)	7.31 score Standard Deviation 1.25	7.27 score Standard Deviation 1.04
Change of Mood Scale Scores Over the Course of the Treatment Week 2 (run-in)	7.53 score Standard Deviation 1.21	7.49 score Standard Deviation 1.10
Change of Mood Scale Scores Over the Course of the Treatment Week 3 (treatment)	7.66 score Standard Deviation 1.05	7.46 score Standard Deviation 1.13
Change of Mood Scale Scores Over the Course of the Treatment Week 4 (treatment)	7.77 score Standard Deviation 1.25	7.53 score Standard Deviation 1.15
Change of Mood Scale Scores Over the Course of the Treatment Week 5 (treatment)	7.73 score Standard Deviation 1.17	7.50 score Standard Deviation 1.24
Change of Mood Scale Scores Over the Course of the Treatment Week 6 (treatment)	7.90 score Standard Deviation 1.10	7.40 score Standard Deviation 1.21
Change of Mood Scale Scores Over the Course of the Treatment Week 7 (treatment)	7.77 score Standard Deviation 1.30	7.55 score Standard Deviation 1.22

SECONDARY outcome

Timeframe: Daily for 2 weeks before treatment intake and 5 weeks during treatment intake

Population: PerProtocol population included all randomized participants that satisfied inclusion/exclusion criteria and had no major protocol deviations (total 113; Lpc-37 n=55; placebo n=58). For individual endpoints, participants were excluded if they showed deviations that were considered to possibly affect the endpoint in question (number analyzed varies).

Efficacy of the intake of Lpc-37 on the increase of perceived productivity scores over the course of the treatment

Measured with a daily online diary. Productivity was rated by participants on an 11-point scale (0-10; "not at all" to "very") and monitored through the wash-out phase (week 1 and 2) and the subsequent treatment phase (weeks 3-7). Higher scores indicate a higher perceived productivity. Efficacy is defined as an increase, or (in case of a general decrease) reduced decrease for the active treatment group as compared to the placebo group and operationalized as the interaction between time and treatment group.Time is coded as a continuous variable with one value for each day and participant. The values reflect summary measures for perceived productivity on a scale from 0 to 10 for the averaged ratings per participant and week.

Outcome measures

Measure	Lpc-37 n=44 Participants Verum: Lacticaseibacillus paracasei Lpc-37 Ingredients: Lacticaseibacillus paracasei Lpc-37 at 1,75 x 10\^10 colony forming units (CFU) per day, microcrystalline cellulose, magnesium stearate, silicon dioxide Participants took one capsule of the IP every morning for 5 weeks, 30 minutes before breakfast or their first meal of the day, with a glass of plain (non-sparkling) water. Participants were stratified for both groups by gender and underlying chronic stress, as assessed using the Trier Inventory for Chronic Stress (TICS).	Placebo n=47 Participants Placebo: capsule manufactured to mimic Lpc-37 capsule Ingredients: microcrystalline cellulose, magnesium stearate, silicon dioxide Participants took one capsule of the IP every morning for 5 weeks, 30 minutes before breakfast or their first meal of the day, with a glass of plain (non-sparkling) water. Participants were stratified by gender and stress level to both groups.
Change of Perceived Productivity Scores Over the Course of the Treatment Week 1 (run-in)	6.98 score Standard Deviation 1.02	7.15 score Standard Deviation 1.07
Change of Perceived Productivity Scores Over the Course of the Treatment Week 2 (run-in)	7.34 score Standard Deviation 1.06	7.29 score Standard Deviation 1.03
Change of Perceived Productivity Scores Over the Course of the Treatment Week 3 (treatment)	7.53 score Standard Deviation 0.97	7.30 score Standard Deviation 1.01
Change of Perceived Productivity Scores Over the Course of the Treatment Week 4 (treatment)	7.48 score Standard Deviation 1.19	7.34 score Standard Deviation 1.18
Change of Perceived Productivity Scores Over the Course of the Treatment Week 5 (treatment)	7.59 score Standard Deviation 1.04	7.43 score Standard Deviation 1.17
Change of Perceived Productivity Scores Over the Course of the Treatment Week 6 (treatment)	7.57 score Standard Deviation 1.13	7.31 score Standard Deviation 1.22
Change of Perceived Productivity Scores Over the Course of the Treatment Week 7 (treatment)	7.50 score Standard Deviation 1.17	7.32 score Standard Deviation 1.25

SECONDARY outcome

Timeframe: Baseline (average of 2 days before first product intake) and end of study (average of 2 days before last product intake)

Population: PerProtocol population included all randomized participants that satisfied inclusion/exclusion criteria and had no major protocol deviations (total 113; Lpc-37 n=55; placebo n=58). For individual endpoints, participants were excluded if they showed deviations that were considered to possibly affect the endpoint in question (number analyzed varies).

Efficacy of the intake of Lpc-37 on the reduction of the difference of Cortisol Awakening Response (CAR) area under the curve with respect to the ground (AUCg) values to the respective mean before and after 5 weeks of treatment.

The CAR is summarized in the variables AUCg, AUCi, mean increase and peak value. These cortisol indices are frequently used to describe hypothalamic-pituitary-adrenal axis activity and represent information either of the total cortisol production or of the change in cortisol levels. AUCg is the total area under the curve of all measurements (i.e., the intensity or magnitude of the response).

Efficacy for the CAR variables AUCg is defined in terms of a normalization: Number of participants with normal values (between first and third quantile of reference measures) and numbers of participants with low or high values are compared before treatment and after treatment. More participants in the normal range after treatment is defined as efficacy.

Outcome measures

Measure	Lpc-37 n=53 Participants Verum: Lacticaseibacillus paracasei Lpc-37 Ingredients: Lacticaseibacillus paracasei Lpc-37 at 1,75 x 10\^10 colony forming units (CFU) per day, microcrystalline cellulose, magnesium stearate, silicon dioxide Participants took one capsule of the IP every morning for 5 weeks, 30 minutes before breakfast or their first meal of the day, with a glass of plain (non-sparkling) water. Participants were stratified for both groups by gender and underlying chronic stress, as assessed using the Trier Inventory for Chronic Stress (TICS).	Placebo n=55 Participants Placebo: capsule manufactured to mimic Lpc-37 capsule Ingredients: microcrystalline cellulose, magnesium stearate, silicon dioxide Participants took one capsule of the IP every morning for 5 weeks, 30 minutes before breakfast or their first meal of the day, with a glass of plain (non-sparkling) water. Participants were stratified by gender and stress level to both groups.
The Change of the Difference From Baseline and 5 Weeks of Treatment to the Respective Mean of CAR AUCg Measures Baseline (<25% quantile)	6 number of participants	12 number of participants
The Change of the Difference From Baseline and 5 Weeks of Treatment to the Respective Mean of CAR AUCg Measures Baseline (25% - 75% quantile)	36 number of participants	30 number of participants
The Change of the Difference From Baseline and 5 Weeks of Treatment to the Respective Mean of CAR AUCg Measures Baseline (>75% quantile)	11 number of participants	13 number of participants
The Change of the Difference From Baseline and 5 Weeks of Treatment to the Respective Mean of CAR AUCg Measures End of Study (<25% quantile)	11 number of participants	7 number of participants
The Change of the Difference From Baseline and 5 Weeks of Treatment to the Respective Mean of CAR AUCg Measures End of Study (25% - 75% quantile)	28 number of participants	35 number of participants
The Change of the Difference From Baseline and 5 Weeks of Treatment to the Respective Mean of CAR AUCg Measures End of Study (>75% quantile)	14 number of participants	13 number of participants

SECONDARY outcome

Timeframe: Baseline (average of 2 days before first product intake) and end of study (average of 2 days before last product intake)

Population: PerProtocol population included all randomized participants that satisfied inclusion/exclusion criteria and had no major protocol deviations (total 113; Lpc-37 n=55; placebo n=58). For individual endpoints, participants were excluded if they showed deviations that were considered to possibly affect the endpoint in question (number analyzed varies).

Efficacy of the intake of Lpc-37 on the reduction of the difference of CAR area under the curve with respect to the increase (AUCi) values to the respective mean before and after the treatment.

The CAR is summarized in the variables AUCg, AUCi, mean increase and peak value. These cortisol indices are frequently used to describe hypothalamic-pituitary-adrenal axis activity and represent information either of the total cortisol production or of the change in cortisol levels. AUCi is calculated with reference to the baseline measurement and it ignores the distance from zero for all measurements and emphasizes the changes over time. Efficacy for the CAR variables AUCi is defined in terms of a normalization: Number of participants with normal values (between first and third quantile of reference measures) and numbers of participants with low or high values are compared before treatment and after treatment. More participants in the normal range after treatment is defined as efficacy.

Outcome measures

Measure	Lpc-37 n=53 Participants Verum: Lacticaseibacillus paracasei Lpc-37 Ingredients: Lacticaseibacillus paracasei Lpc-37 at 1,75 x 10\^10 colony forming units (CFU) per day, microcrystalline cellulose, magnesium stearate, silicon dioxide Participants took one capsule of the IP every morning for 5 weeks, 30 minutes before breakfast or their first meal of the day, with a glass of plain (non-sparkling) water. Participants were stratified for both groups by gender and underlying chronic stress, as assessed using the Trier Inventory for Chronic Stress (TICS).	Placebo n=55 Participants Placebo: capsule manufactured to mimic Lpc-37 capsule Ingredients: microcrystalline cellulose, magnesium stearate, silicon dioxide Participants took one capsule of the IP every morning for 5 weeks, 30 minutes before breakfast or their first meal of the day, with a glass of plain (non-sparkling) water. Participants were stratified by gender and stress level to both groups.
The Change of the Difference From Baseline and 5 Weeks of Treatment to the Respective Mean of Cortisol Awakening Response (CAR) AUCi Measures Baseline (<25% quantile)	16 number of participants	22 number of participants
The Change of the Difference From Baseline and 5 Weeks of Treatment to the Respective Mean of Cortisol Awakening Response (CAR) AUCi Measures Baseline (25% - 75% quantile)	34 number of participants	28 number of participants
The Change of the Difference From Baseline and 5 Weeks of Treatment to the Respective Mean of Cortisol Awakening Response (CAR) AUCi Measures Baseline (>75% quantile)	3 number of participants	5 number of participants
The Change of the Difference From Baseline and 5 Weeks of Treatment to the Respective Mean of Cortisol Awakening Response (CAR) AUCi Measures End of Study (<25% quantile)	15 number of participants	15 number of participants
The Change of the Difference From Baseline and 5 Weeks of Treatment to the Respective Mean of Cortisol Awakening Response (CAR) AUCi Measures End of Study (25% - 75% quantile)	34 number of participants	36 number of participants
The Change of the Difference From Baseline and 5 Weeks of Treatment to the Respective Mean of Cortisol Awakening Response (CAR) AUCi Measures End of Study (>75% quantile)	4 number of participants	4 number of participants

SECONDARY outcome

Timeframe: Baseline (average of 2 days before first product intake) and end of study (average of 2 days before last product intake)

Population: PerProtocol population included all randomized participants that satisfied inclusion/exclusion criteria and had no major protocol deviations (total 113; Lpc-37 n=55; placebo n=58). For individual endpoints, participants were excluded if they showed deviations that were considered to possibly affect the endpoint in question (number analyzed varies).

Efficacy of the intake of Lpc-37 on the reduction of the difference of Cortisol at Awakening values to the respective mean before and after 5 weeks of treatment

Efficacy for the CAR variable cortisol at awakening is defined in terms of a normalization: Number of participants with normal values (between first and third quantile of reference measures) and numbers of participants with low or high values are compared before treatment and after treatment. More participants in the normal range after treatment is defined as efficacy.

Outcome measures

Measure	Lpc-37 n=53 Participants Verum: Lacticaseibacillus paracasei Lpc-37 Ingredients: Lacticaseibacillus paracasei Lpc-37 at 1,75 x 10\^10 colony forming units (CFU) per day, microcrystalline cellulose, magnesium stearate, silicon dioxide Participants took one capsule of the IP every morning for 5 weeks, 30 minutes before breakfast or their first meal of the day, with a glass of plain (non-sparkling) water. Participants were stratified for both groups by gender and underlying chronic stress, as assessed using the Trier Inventory for Chronic Stress (TICS).	Placebo n=55 Participants Placebo: capsule manufactured to mimic Lpc-37 capsule Ingredients: microcrystalline cellulose, magnesium stearate, silicon dioxide Participants took one capsule of the IP every morning for 5 weeks, 30 minutes before breakfast or their first meal of the day, with a glass of plain (non-sparkling) water. Participants were stratified by gender and stress level to both groups.
The Change of the Difference From Baseline and 5 Weeks of Treatment to the Respective Mean of Cortisol at Awakening Measures Baseline (<25% quantile)	14 number of participants	16 number of participants
The Change of the Difference From Baseline and 5 Weeks of Treatment to the Respective Mean of Cortisol at Awakening Measures Baseline (25% - 75% quantile)	31 number of participants	26 number of participants
The Change of the Difference From Baseline and 5 Weeks of Treatment to the Respective Mean of Cortisol at Awakening Measures Baseline (>75% quantile)	8 number of participants	13 number of participants
The Change of the Difference From Baseline and 5 Weeks of Treatment to the Respective Mean of Cortisol at Awakening Measures End of Study (<25% quantile)	19 number of participants	12 number of participants
The Change of the Difference From Baseline and 5 Weeks of Treatment to the Respective Mean of Cortisol at Awakening Measures End of Study (25% - 75% quantile)	26 number of participants	34 number of participants
The Change of the Difference From Baseline and 5 Weeks of Treatment to the Respective Mean of Cortisol at Awakening Measures End of Study (>75% quantile)	8 number of participants	9 number of participants

SECONDARY outcome

Timeframe: Baseline (average of 2 days before first product intake) and end of study (average of 2 days before last product intake

Population: PerProtocol population included all randomized participants that satisfied inclusion/exclusion criteria and had no major protocol deviations (total 113; Lpc-37 n=55; placebo n=58). For individual endpoints, participants were excluded if they showed deviations that were considered to possibly affect the endpoint in question (number analyzed varies).

Efficacy of the intake of Lpc-37 on the reduction of the difference of cortisol at 8 pm values to the respective mean before and after 5 weeks of treatment

Efficacy for the CAR variable cortisol at 8 pm is defined in terms of a normalization: Number of participants with normal values (between first and third quantile of reference measures) and numbers of participants with low or high values are compared before treatment and after treatment. More participants in the normal range after treatment is defined as efficacy.

Outcome measures

Measure	Lpc-37 n=53 Participants Verum: Lacticaseibacillus paracasei Lpc-37 Ingredients: Lacticaseibacillus paracasei Lpc-37 at 1,75 x 10\^10 colony forming units (CFU) per day, microcrystalline cellulose, magnesium stearate, silicon dioxide Participants took one capsule of the IP every morning for 5 weeks, 30 minutes before breakfast or their first meal of the day, with a glass of plain (non-sparkling) water. Participants were stratified for both groups by gender and underlying chronic stress, as assessed using the Trier Inventory for Chronic Stress (TICS).	Placebo n=55 Participants Placebo: capsule manufactured to mimic Lpc-37 capsule Ingredients: microcrystalline cellulose, magnesium stearate, silicon dioxide Participants took one capsule of the IP every morning for 5 weeks, 30 minutes before breakfast or their first meal of the day, with a glass of plain (non-sparkling) water. Participants were stratified by gender and stress level to both groups.
The Change of the Difference From Baseline and 5 Weeks of Treatment to the Respective Mean of CAR 8pm Measures Baseline (<25% quantile)	4 number of participants	6 number of participants
The Change of the Difference From Baseline and 5 Weeks of Treatment to the Respective Mean of CAR 8pm Measures Baseline (25% - 75% quantile)	20 number of participants	23 number of participants
The Change of the Difference From Baseline and 5 Weeks of Treatment to the Respective Mean of CAR 8pm Measures Baseline (>75% quantile)	29 number of participants	26 number of participants
The Change of the Difference From Baseline and 5 Weeks of Treatment to the Respective Mean of CAR 8pm Measures End of Study (<25% quantile)	3 number of participants	7 number of participants
The Change of the Difference From Baseline and 5 Weeks of Treatment to the Respective Mean of CAR 8pm Measures End of Study (25% - 75% quantile)	28 number of participants	18 number of participants
The Change of the Difference From Baseline and 5 Weeks of Treatment to the Respective Mean of CAR 8pm Measures End of Study (>75% quantile)	22 number of participants	30 number of participants

Adverse Events

Lpc-37

Serious events: 0 serious events

Other events: 29 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 26 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Lpc-37 n=59 participants at risk Verum: Lacticaseibacillus paracasei Lpc-37 Ingredients: Lacticaseibacillus paracasei Lpc-37 at 1,75 x 10\^10 colony forming units (CFU) per day, microcrystalline cellulose, magnesium stearate, silicon dioxide Participants took one capsule of the IP every morning for 5 weeks, 30 minutes before breakfast or their first meal of the day, with a glass of plain (non-sparkling) water. Participants were stratified by gender and stress level to both groups.	Placebo n=59 participants at risk Placebo: capsule manufactured to mimic Lpc-37 capsule Ingredients: microcrystalline cellulose, magnesium stearate, silicon dioxide Participants took one capsule of the IP every morning for 5 weeks, 30 minutes before breakfast or their first meal of the day, with a glass of plain (non-sparkling) water. Participants were stratified by gender and stress level to both groups.
Respiratory, thoracic and mediastinal disorders common cold	8.5% 5/59 • Number of events 8 • Adverse event (AE) data was collected daily during the 5-week intervention period and tracked when the AE continued at the end of the study (up to 30 days afterwards) AE reporting was done by the Investigator or her designees. All AEs were collected on the paper case report forms. Variables recorded for each AE: Description of the event, onset and resolution (date and time), whether the AE is ongoing at the end of the study, intensity (mild, moderate, severe), therapy of event, action taken, outcome, causality (definitely, probably, possibly, unlikely, not related, not assessable) and whether it constitutes an Serious Adverse Event (SAE) or not.	6.8% 4/59 • Number of events 4 • Adverse event (AE) data was collected daily during the 5-week intervention period and tracked when the AE continued at the end of the study (up to 30 days afterwards) AE reporting was done by the Investigator or her designees. All AEs were collected on the paper case report forms. Variables recorded for each AE: Description of the event, onset and resolution (date and time), whether the AE is ongoing at the end of the study, intensity (mild, moderate, severe), therapy of event, action taken, outcome, causality (definitely, probably, possibly, unlikely, not related, not assessable) and whether it constitutes an Serious Adverse Event (SAE) or not.
Respiratory, thoracic and mediastinal disorders sore throat	10.2% 6/59 • Number of events 9 • Adverse event (AE) data was collected daily during the 5-week intervention period and tracked when the AE continued at the end of the study (up to 30 days afterwards) AE reporting was done by the Investigator or her designees. All AEs were collected on the paper case report forms. Variables recorded for each AE: Description of the event, onset and resolution (date and time), whether the AE is ongoing at the end of the study, intensity (mild, moderate, severe), therapy of event, action taken, outcome, causality (definitely, probably, possibly, unlikely, not related, not assessable) and whether it constitutes an Serious Adverse Event (SAE) or not.	13.6% 8/59 • Number of events 10 • Adverse event (AE) data was collected daily during the 5-week intervention period and tracked when the AE continued at the end of the study (up to 30 days afterwards) AE reporting was done by the Investigator or her designees. All AEs were collected on the paper case report forms. Variables recorded for each AE: Description of the event, onset and resolution (date and time), whether the AE is ongoing at the end of the study, intensity (mild, moderate, severe), therapy of event, action taken, outcome, causality (definitely, probably, possibly, unlikely, not related, not assessable) and whether it constitutes an Serious Adverse Event (SAE) or not.
Nervous system disorders headache	37.3% 22/59 • Number of events 34 • Adverse event (AE) data was collected daily during the 5-week intervention period and tracked when the AE continued at the end of the study (up to 30 days afterwards) AE reporting was done by the Investigator or her designees. All AEs were collected on the paper case report forms. Variables recorded for each AE: Description of the event, onset and resolution (date and time), whether the AE is ongoing at the end of the study, intensity (mild, moderate, severe), therapy of event, action taken, outcome, causality (definitely, probably, possibly, unlikely, not related, not assessable) and whether it constitutes an Serious Adverse Event (SAE) or not.	25.4% 15/59 • Number of events 34 • Adverse event (AE) data was collected daily during the 5-week intervention period and tracked when the AE continued at the end of the study (up to 30 days afterwards) AE reporting was done by the Investigator or her designees. All AEs were collected on the paper case report forms. Variables recorded for each AE: Description of the event, onset and resolution (date and time), whether the AE is ongoing at the end of the study, intensity (mild, moderate, severe), therapy of event, action taken, outcome, causality (definitely, probably, possibly, unlikely, not related, not assessable) and whether it constitutes an Serious Adverse Event (SAE) or not.
Gastrointestinal disorders stomach ache	8.5% 5/59 • Number of events 8 • Adverse event (AE) data was collected daily during the 5-week intervention period and tracked when the AE continued at the end of the study (up to 30 days afterwards) AE reporting was done by the Investigator or her designees. All AEs were collected on the paper case report forms. Variables recorded for each AE: Description of the event, onset and resolution (date and time), whether the AE is ongoing at the end of the study, intensity (mild, moderate, severe), therapy of event, action taken, outcome, causality (definitely, probably, possibly, unlikely, not related, not assessable) and whether it constitutes an Serious Adverse Event (SAE) or not.	11.9% 7/59 • Number of events 10 • Adverse event (AE) data was collected daily during the 5-week intervention period and tracked when the AE continued at the end of the study (up to 30 days afterwards) AE reporting was done by the Investigator or her designees. All AEs were collected on the paper case report forms. Variables recorded for each AE: Description of the event, onset and resolution (date and time), whether the AE is ongoing at the end of the study, intensity (mild, moderate, severe), therapy of event, action taken, outcome, causality (definitely, probably, possibly, unlikely, not related, not assessable) and whether it constitutes an Serious Adverse Event (SAE) or not.
Infections and infestations Head cold	3.4% 2/59 • Number of events 2 • Adverse event (AE) data was collected daily during the 5-week intervention period and tracked when the AE continued at the end of the study (up to 30 days afterwards) AE reporting was done by the Investigator or her designees. All AEs were collected on the paper case report forms. Variables recorded for each AE: Description of the event, onset and resolution (date and time), whether the AE is ongoing at the end of the study, intensity (mild, moderate, severe), therapy of event, action taken, outcome, causality (definitely, probably, possibly, unlikely, not related, not assessable) and whether it constitutes an Serious Adverse Event (SAE) or not.	6.8% 4/59 • Number of events 4 • Adverse event (AE) data was collected daily during the 5-week intervention period and tracked when the AE continued at the end of the study (up to 30 days afterwards) AE reporting was done by the Investigator or her designees. All AEs were collected on the paper case report forms. Variables recorded for each AE: Description of the event, onset and resolution (date and time), whether the AE is ongoing at the end of the study, intensity (mild, moderate, severe), therapy of event, action taken, outcome, causality (definitely, probably, possibly, unlikely, not related, not assessable) and whether it constitutes an Serious Adverse Event (SAE) or not.
Respiratory, thoracic and mediastinal disorders Cough	1.7% 1/59 • Number of events 2 • Adverse event (AE) data was collected daily during the 5-week intervention period and tracked when the AE continued at the end of the study (up to 30 days afterwards) AE reporting was done by the Investigator or her designees. All AEs were collected on the paper case report forms. Variables recorded for each AE: Description of the event, onset and resolution (date and time), whether the AE is ongoing at the end of the study, intensity (mild, moderate, severe), therapy of event, action taken, outcome, causality (definitely, probably, possibly, unlikely, not related, not assessable) and whether it constitutes an Serious Adverse Event (SAE) or not.	5.1% 3/59 • Number of events 3 • Adverse event (AE) data was collected daily during the 5-week intervention period and tracked when the AE continued at the end of the study (up to 30 days afterwards) AE reporting was done by the Investigator or her designees. All AEs were collected on the paper case report forms. Variables recorded for each AE: Description of the event, onset and resolution (date and time), whether the AE is ongoing at the end of the study, intensity (mild, moderate, severe), therapy of event, action taken, outcome, causality (definitely, probably, possibly, unlikely, not related, not assessable) and whether it constitutes an Serious Adverse Event (SAE) or not.
Cardiac disorders Vertigo	3.4% 2/59 • Number of events 2 • Adverse event (AE) data was collected daily during the 5-week intervention period and tracked when the AE continued at the end of the study (up to 30 days afterwards) AE reporting was done by the Investigator or her designees. All AEs were collected on the paper case report forms. Variables recorded for each AE: Description of the event, onset and resolution (date and time), whether the AE is ongoing at the end of the study, intensity (mild, moderate, severe), therapy of event, action taken, outcome, causality (definitely, probably, possibly, unlikely, not related, not assessable) and whether it constitutes an Serious Adverse Event (SAE) or not.	6.8% 4/59 • Number of events 4 • Adverse event (AE) data was collected daily during the 5-week intervention period and tracked when the AE continued at the end of the study (up to 30 days afterwards) AE reporting was done by the Investigator or her designees. All AEs were collected on the paper case report forms. Variables recorded for each AE: Description of the event, onset and resolution (date and time), whether the AE is ongoing at the end of the study, intensity (mild, moderate, severe), therapy of event, action taken, outcome, causality (definitely, probably, possibly, unlikely, not related, not assessable) and whether it constitutes an Serious Adverse Event (SAE) or not.
General disorders Discomfort/Complaints related to the menstrual cycle	3.4% 2/59 • Number of events 3 • Adverse event (AE) data was collected daily during the 5-week intervention period and tracked when the AE continued at the end of the study (up to 30 days afterwards) AE reporting was done by the Investigator or her designees. All AEs were collected on the paper case report forms. Variables recorded for each AE: Description of the event, onset and resolution (date and time), whether the AE is ongoing at the end of the study, intensity (mild, moderate, severe), therapy of event, action taken, outcome, causality (definitely, probably, possibly, unlikely, not related, not assessable) and whether it constitutes an Serious Adverse Event (SAE) or not.	5.1% 3/59 • Number of events 3 • Adverse event (AE) data was collected daily during the 5-week intervention period and tracked when the AE continued at the end of the study (up to 30 days afterwards) AE reporting was done by the Investigator or her designees. All AEs were collected on the paper case report forms. Variables recorded for each AE: Description of the event, onset and resolution (date and time), whether the AE is ongoing at the end of the study, intensity (mild, moderate, severe), therapy of event, action taken, outcome, causality (definitely, probably, possibly, unlikely, not related, not assessable) and whether it constitutes an Serious Adverse Event (SAE) or not.

Additional Information

Elaine Patterson, Ph. D.

DuPont Nutrition and Biosciences

Phone: +358-40-4827-626

Email: elaine.patterson@dupont.com

Results disclosure agreements

• Principal investigator is a sponsor employee Overall Non-disclosure and Confidentiality Agreement
• Publication restrictions are in place

Restriction type: OTHER