EXTRAMEL® is a proprietary freeze-dried melon juice concentrate obtained by physical treatment (crushing of the melon, recovery of the pulp, centrifugation, filtration, freeze-drying) of a specific variety of melon (not a genetically modified organism) which contains high levels of SOD and other antioxidants (US Patent No 5 616 323). As SOD is very sensitive to oxygen, high temperature and acidity, the melon juice concentrate has to be coated. The product used in the study (EXTRAMEL® microgranules) was coated with palm oil. The dietary supplements given to the volunteers were small hard capsules containing 10 mg Extramel® (140 IU of SOD ) and starch for the verum (EXT) and starch only for the placebo (P).
The volunteers assigned by randomisation in two groups of 35 were given a food supplement (EXT) or a placebo (P) for 28 days: one capsule per day taken in the morning. The capsules were indistinguishable and were administered in a double blind approach.
Methods: Psychometric tools
In order to evaluate the signs and symptoms of perceived stress and fatigue, the neurobehavioral sphere of the volunteers was explored. Moreover, their own perception of stress and its impact on their quality of life and sleep were evaluated. Four validated and well-known evaluation scales were then chosen:
1. Ferreri Anxiety Rating Diagram (FARD) [13, 14] explores four poles divided in three items:
- Somatic pole (attitude, neurovegetative troubles, pain),
- Relational pole (apprehension, internal tension, difficulty of contact),
- Vigilance pole (irritability, sensorial troubles, sleep troubles),
- Cognitive pole (concentration, weariness, doubt-indecision),
with a total of 12 questions and a score from 0 to 72;
2. Cohen Perceived Stress scale (PSS-14)  evaluates the perceived stress during the last two weeks with 14 questions and a score from 14 to 70;
Health Survey  allows to measure eight aspects of the quality of life: general physical and mental health state (fatigue), physical and social functioning, physical and emotional health, pain and vitality. The SF-12 questionnaire is composed of 12 questions with a score from 3 to 38;
4. Epworth Sleepiness Scale  is a questionnaire intended to measure daytime sleepiness composed by eight questions with a score from 0 to 24.
The Beck Depression Inventory (BDI) , a 13 question multiple choice self-report inventory, which is one of the most widely used instruments for measuring the severity of depression, was used to avoid the inclusion of depressive volunteers.
The clinical trial was an intervention pilot study based on individual evaluation scales. The protocol followed was randomized, double blind and placebo controlled. It was approved by the Comité de Protection des Personnes Ouest III, the ethical committee of Poitiers, France under the number 2006-A00677-44 to be conducted by Dr Thierry Cantin.
A call for volunteers was made in the region of the investigation centre (Poitiers area, Poitou, 86, France) and the volunteers for the study were pre-screened by the investigator.
The inclusion criteria were to be between 30 to 55 years old, to have a BMI (Body Mass Index) ≤ 30, to have a stable professional activity for more than one year, to perceive a certain level of stress & fatigue, to be in full health, not taking any drugs or dietary supplements, not taking anti-stress or anti-fatigue drinks.
The exclusion criteria were to be pregnant or breast-feeding, to have a previous case of psychiatric disease, to have pathologies ongoing or active during the last month, to have received medical treatment (allopathic or homeopathic) during the previous month, to have taken a dietary supplement during the last month, to be in a stressful situation during the next month (wedding, birth, scheduled hospitalisation, important exam...).
Acceptable volunteers were called in for a screening and baseline evaluation using the five evaluation scales previously described: FARD, Epworth, PSS-14, SF-12 and BDI scale. Then, 70 volunteers were definitively included and participated in the clinical trial. These volunteers provided a written informed consent.
The volunteers were tested three times during a visit to the doctor. The first time was before the supplementation (D0), corresponding to the screening evaluation. A test was planned 7 days (D7) after taking the supplement and another one at the end of the trial (D28). The evaluation scales were filled out by the volunteers themselves. During every consultation, the doctor made a general clinical exam (arterial tone and cardiac frequency measure) and filled up an event journal with remarks on the volunteers, eventual undercurrent effects, the eventual pathologies and their associated treatment.
Method of Screening the Volunteers
Axis were determined by combining the different scales:
Physical Axis composed by FARD somatic pole (0 - 18), FARD vigilance pole (0 - 18) and SF-12 scale (3 - 38) with a total score from 3 to 74;
Cognitive Axis composed by FARD cognitive pole (0 - 18) with a total score from 0 to 18;
Relational Axis composed by FARD relational pole (0 - 18) with a total score from 0 to 18;
Perceived Stress Axis composed by Epworth sleepiness scale (0 - 24) and Cohen's PSS-14 perceived stress scale (14 - 70) with a total score form 14 to 94. To be included, the volunteers had to get scores within the following parameters: BDI < 5; Physical Axis > 15/74; Cognitive Axis > 5/18; Relational Axis > 5/18; Perceived Stress Axis > 33/94.
The means of each score for the volunteers were: Physical Axis = 24.95; Cognitive Axis = 6.27; Relational Axis = 5.89; Perceived Stress Axis = 40.7.
The data were expressed as means ± SD of the evolution of the scores on each scale between D0 and D7 and between D0 and D28 in absolute and relative values. The paired Student's t-Test was used to analyse each group relative to the amplitude of variation between D0 and D7 and D0 and D28 and to compare results between groups at D0, D7 and D28.