Stress & Anxiety Dampening Effects of a Probiotic Supplement Compared to Placebo in Healthy Subjects

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

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

Time frame: 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 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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 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).

Time frame: 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 reduction of the increase of salivary Alpha-Amylase (sAA) in response to the TSST compared to placebo.

Time frame: 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.

Time frame: 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 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

Time frame: 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.

Time frame: 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 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.

Time frame: 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 the systolic BP in response to the TSST compared to placebo.

Time frame: 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 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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).

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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).