# Abstract

 

## Background Exhaustive exercise causes muscle damage accompanied by oxidative stress and inflammation leading to muscle fatigue and muscle soreness. Lemon verbena leaves, commonly used as tea and refreshing beverage, demonstrated antioxidant and anti-inflammatory properties. The aim of this study was to investigate the effects of a proprietary lemon verbena extract (Recoverben®) on muscle strength and recovery after exhaustive exercise in comparison to a placebo product. 

## Methods The study was performed as a randomized, placebo-controlled, double-blind study with parallel design. Forty-four healthy males and females, which were 22--50 years old and active in sports, were randomized to 400 mg lemon verbena extract once daily or placebo. The 15 days intervention was divided into 10 days supplementation prior to the exhaustive exercise day (intensive jump-protocol), one day during the test and four days after. Muscle strength (MVC), muscle damage (CK), oxidative stress (GPx), inflammation (IL6) and volunteer-reported muscle soreness intensity were assessed pre and post exercise. 

## Results Participants in the lemon verbena group benefited from less muscle damage as well as faster and full recovery. Compared to placebo, lemon verbena extract receiving participants had significantly less exercise-related loss of muscle strength (*p* = 0.0311) over all timepoints, improved glutathione peroxidase activity by trend (*p* = 0.0681) and less movement induced pain (*p* = 0.0788) by trend. Creatine kinase and IL-6 didn't show significant discrimmination between groups. 

## Conclusion Lemon verbena extract (Recoverben®) has been shown to be a safe and well-tolerated natural sports ingredient, by reducing muscle damage after exhaustive exercise. 

## Trial registration The trial was registered in the clinical trials registry (clinical trial.gov [NCT02923102](#)). Registered 28 September 2016 # Results 

## Group characteristics Out of 44 subjects allocated to intervention, 40 subjects (19 men and 21 women) completed the study according to the protocol (full analysis set; FAS). Four subjects dropped out after start of supplementation and before efficacy testing. Three of these suffered from a common cold, which did not allow them to perform the exhaustive exercise test, and one dropped out due to personal decision. Thirty-seven subjects were analyzed for valid case analysis set (VCAS). One subject had a strong common cold during the exhaustive exercise test, which may have influenced biomarker results. Another subject did not meet compliance criteria for study product intake and the third subject had major deviation of the exhaustive exercise protocol. As these three subjects did meet exclusion criteria for VCAS analysis, they were not considered in final analysis (VCAS). Gender, age, BMI, blood routine markers, and blood pressure did not differ significantly between the groups prior to the study. Subject characteristics are summarized in Table [2](#). The nutrition frequency questionnaire scores were 45.35 ± 10.51 points in the lemon verbena group and 42.65 ± 11.33 points in the placebo group (*p* = 0.4597). Most subjects consumed between two and four portions fruits plus vegetables per day (lemon verbena: 82%, placebo: 70%). Intake of fruit and vegetables, as supplier for polyphenols, were comparable between groups. The protocol compliance of study product intake was very good. For VCAS, all subjects met the compliance criterion ≥85% and ≤115% of study preparation consumed (lemon verbena group: 102 ± 5%, placebo: 101 ± 2%). For FAS, one subject had a compliance >115% since much less products remained, bringing up uncertainty about correct intake, which was the reason for exclusion from VCAS. Borg scale data after exhaustive exercise and jump repetitions were not significantly different between groups (*p* = 0.8997, *p* = 0.1561). Therefore, burden of subjects by the exhaustive exercise and jump protocol was comparable between groups, so a comparable stress could be expected. ::::table-wrap

::: caption
Subject characteristics at screening for FAS (*N* = 40, 19 men, 21
women)
:::

______________________________________________________________________

Parameter Lemon verbena Placebo Inclusion criteria/Reference range
[unit] (*N* = 20 59% men, 41% women) (*N* = 20 40% men, 60% women)

______________________________________________________________________

Age Mean 31.7 30.6 22--50
[years]

Sd 8.8 9.3

BMI Mean 22.67 23.0 19--30
[kg/m^2^]

Sd 2.3 2.5

Activity Mean 3209 2470.0 --
[MET min/week]

Sd 3957.0 2521

CHOL Mean 172.5 180.0 100--200
[mg/dL]

Sd 23.0 31.85

TG Mean 89.68 82.14 \<160
[mg/dL]

Sd 43.53 24.71

HDL Mean 58.91 58.95 >40
[mg/dL]

Sd 6.487 14.24

LDL Mean 93.86 109.5 \<150
[mg/dL]

Sd 16.32 28.7

Glucose Mean 87.55 86.14 60--100
[mg/dL]

Sd 8.405 4.96

SBP Mean 121.6 121.6 120--129
[mmhg]

Sd 12.8 12.8

DBP Mean 75.8 70.6 80--84
[mmhg]



## Sd 8.8 10.5

*BMI* body mass index, *MET* metabolic equivalent of task, *CHOL*
cholesterol, *TG* triglycerides, *HDL* high-density lipoprotein, *LDL*
low-density lipoprotein, *SBP* systolic blood pressure, *DBP* diastolic
blood pressure:::: 

## Muscle function testing - maximal voluntary contraction MVC was significantly less reduced after exercise in the lemon verbena group than in the placebo group (*p* = 0.0311), with significant time effect (*p* = 0.0051), (Fig. [2](#), Table [3](#)). In the lemon verbena group, muscle strength was completely back to baseline after 48 h, whereas strength was still reduced at that time point in the placebo group. <figure> <p><img src="" /></p> <figcaption>Maximal voluntary contraction. Delta MVC [N] (Mean ± 95% CI; product effect: <em>p</em> = 0.0311) * indicating significance against baseline; & indicating significant group differeneces</figcaption> </figure> ::::table-wrap
::: caption
Statistical results within (one way-ANOVA) and between groups (Linear
mixed models with repeated measures or in case of Ret. pain generalized
linear mixed model with poisson distribution for count data) for maximal
voluntary contraction (MVC), movement induced pain (VAS), retrospective
pain (Ret. pain), creatin kinase (CK), gluthation peroxidase (GPxP) and
interleukine-6 (IL-6)
:::

```
              Within group   Between group                  
```

______________________________________________________________________

Lemon verbena Placebo Product effect Time effect\
MVC 0.005 \<0.0001 0.0311 0.0051
VAS \<0.0001 \<0.0001 0.0788 \<0.0001
Ret. pain \<0.0001 \<0.0001 0.782 \<0.0001
CK \<0.0001 \<0.0001 0.9412 \<0.0001
GPxP 0.204 0.5895 0.0681 0.0624:::: 

## Perceived muscle soreness Movement induced pain (VAS) in the lemon verbena group was less pronounced by trend (*p* = 0.0788) with a significant time effect (*p* \< 0.0001) in comparison to the placebo group (Fig. [3](#), Table [3](#)). Retrospective pain was comparable between groups without significant difference (Fig. [4](#)). Both groups showed significant increase in soreness 24, 48, and 72 h after exercise in relation to pre-exercise. <figure> <p><img src="" /></p> <figcaption>Movement induced pain. Movement induced pain (VAS) [cm] (Mean ± 95% CI; product effect: <em>p</em> = 0.0788) * indicating significance against baseline</figcaption> </figure> <figure> <p><img src="" /></p> <figcaption>Retrospective pain. Retrospective pain [score] (Mean ± 95% CI; product effect: <em>p</em> = 0.7820) * indicating significance against baseline</figcaption> </figure> 

## Biochemical analyses 

### Creatine kinase Exercise-induced CK was not significantly different between groups (*p* = 0.9412 with significant time effect (p \< 0.0001) (Fig. [5](#), Table [3](#)). <figure> <p><img src="" /></p> <figcaption>Creatine kinase. Delta Creatine kinase [U/L] (Mean ± 95% CI; product effect: <em>p</em> = 0.9412) * indicating significance against baseline</figcaption> </figure> In the lemon verbena group, CK was significantly increased above baseline at 24 h but not 3- or 48-h post-exercise. In contrast, the placebo group showed significant elevations of CK at all three time points relative to baseline. 

### Glutathione peroxidase The GPxP activity within lemon verbena group was increased by trend compared to placebo group (*p* = 0.0681), with time effect also by trend (*p* = 0.0624), (Fig. [6](#), Table [3](#)). <figure> <p><img src="" /></p> <figcaption>Glutathione peroxidase. Delta Glutathione peroxidase [U/L] (Mean ± 95% CI; product effect: <em>p</em> = 0.0681) * indicating significance against baseline</figcaption> </figure> 

### Interleukin 6 Only distinct increase of IL-6 could be observed after exercise, without significant differences but high inter-individual variability. Differences between groups were not significant (*p* = 0.5824). 

## Safety and tolerability Blood chemistry, vital signs, adverse events, and concomitant medication did not indicate any safety concerns over 15 days. There was no statistical difference between the two groups for adverse events (*p* = 0.231). The most frequent adverse events were headache (lemon verbena: 5%, placebo: 18%) and common cold (lemon verbena 23%, placebo: 23%). None of the adverse events were serious or related to the study products. The intervention was well tolerated.


Extracted trial result:
Outcome: Interleukin 6 (continuous)
Intervention: lemon verbena extract
Comparator: placebo
Intervention group size: 20
Comparator group size: 20
Notes: Numerical values are not given.