Multicentre, Double-blind Study Versus Placebo on Impact and Safety of Extramel® 140 IU on Perceived Stress, Physical and Intellectual Fatigue, Pain Perception if Present, and the Impact on the Quality of Life

• Extramel 10 mg - 140 UI SOD (Dietary supplement): Subjects took one capsule of Extramel® 140 IU, or its corresponding placebo, daily over 12 weeks. Each volunteer was seen for the 3 visits: * visit V1, so-called inclusion visit (D0), * visit V2 at 28 days, tolerance of +/- 3 days, (D28) and * visit V3 at 84 days, tolerance of +/- 3 days, (D84).
• Placebo - Excipient only (Dietary supplement)

Primary outcomes

• Perceived Stress : Change from base line in Cohen PSS 14 scale at V2 and V3 [Evaluation performed at inclusion day (V1), after 4 weeks at D28 (V2) and then at the end of study visit on D84 (V3).]: Evaluation performed by Cohen PSS 14 scale. It should be noted that in order to be included the patient had to present a minimum score of 30 on the Cohen scale.

Secondary outcomes

• Evaluation of evolution of Physical fatigue [Evaluation performed at inclusion day (V1), after 4 weeks at D28 (V2) and then at the end of study visit on D84 (V3).]: Evaluation performed by Prevost subjective fatigue scale and Ruffier test.
• Evaluation of evolution of Intellectual fatigue [Evaluation performed at inclusion day (V1), after 4 weeks at D28 (V2) and then at the end of study visit on D84 (V3).]: Evaluation performed by Stroop test, Reverse Stroop test and 15-words Rey test.
• Evaluation of evolution of pain [Evaluation performed at inclusion day (V1), after 4 weeks at D28 (V2) and then at the end of study visit on D84 (V3).]: Evaluation of subjects' perceived chronic pain (if existing), was performed using a simple visual analog scale (VAS).
• Evaluation of evolution of subject Quality of life [Evaluation performed at inclusion day (V1), after 4 weeks at D28 (V2) and then at the end of study visit on D84 (V3).]: Evaluation of subjects' quality of life, was performed by using Quality of Life SF36 scale.
• Evaluation of evolution of subject Quality of life [Evaluation performed at inclusion day (V1), after 4 weeks at D28 (V2) and then at the end of study visit on D84 (V3).]: Evaluation of subjects' quality of life, was performed by using Hamilton anxiety scale.
• Evaluation of evolution of subject Quality of life [Evaluation performed at inclusion day (V1), after 4 weeks at D28 (V2) and then at the end of study visit on D84 (V3).]: Evaluation of subjects' quality of life, was performed by using Personnal stress profile questionnary.

Other outcomes

• Evaluation of safety [Global safty evaluation performed at the end of study.]: Assessment of the safety performed by analysis of adverse events that occurred throughout the study.

Sex: All, ages: 30 Years to 65 Years, accepts healthy volunteers

Inclusion Criteria:

* Male or female person using an effective contraceptive method, with a negative urine pregnancy test on the inclusion visit for the women of reproductive age.
* Older than 30 years and younger than 65 years
* BMI ≤ 30
* Score greater than 30 on the Cohen perceived stress scale PSS 14.
* Score between 5 and 20 in the Hamilton anxiety scale (excluding the limits).
* Presenting an impact of stress on at least one of the following domains.

  * pain domain with a score greater than 20 millimeters measured on the visual pain evaluation scale,
  * physical condition domain with a score greater than 50 on the Prevost subjective fatigue scale,
  * the psychical condition domain with a global score below 160 in the Stroop test and the reverse Stroop test.
* Stable professional activity since at least 1 year.
* Completely healthy on the day of inclusion, and not taking any medicinal product or dietary supplement with an anti-stress or anti-pain objective.
* Not taking any herbal tea or drink with an anti-stress or anti-pain objective.
* Accepting not to modify his/her dietary habits.
* Having given his/her free, informed and express consent.
* Capable of understanding the nature of the objectives, the consequences of the study and accepting to comply with the protocol requirements.
* Affiliated with a social security insurance or beneficiary of such an insurance system.

Exclusion Criteria:

* Subject presenting an acute pain or pain considered to be incapacitating by the patient him/herself or the observer physician.
* Subject currently under a chronic or acute treatment indicated for stress or anxiety, irrespective of the treatment.
* Subject currently under a chronic or acute treatment indicated for pain problems, irrespective of the treatment.
* Pregnant and/or breast-feeding women.
* Any person who does not satisfy by definition the inclusion criteria.
* Adult protected by the law.
* Any history of psychiatric disease.
* Any pathology in progress or active in the previous month.
* Any administration of a dietary supplement in progress or in the previous month.
* Any subject who within the 3 months following inclusion is likely to experience a major modification of his/her life rhythm (For example marriage, birth of a child, scheduled hospitalization, important exam, etc.) this is left to the discretion of the investigator.

• Results publication: Carillon J, Notin C, Schmitt K, Simoneau G, Lacan D. Dietary supplementation with a superoxide dismutase-melon concentrate reduces stress, physical and mental fatigue in healthy people: a randomised, double-blind, placebo-controlled trial. Nutrients. 2014 Jun 19;6(6):2348-59. doi: 10.3390/nu6062348. PMID 24949549

• Thierry CANTIN, MD, Principal investigator
• Patrick LEPRINCE, MD, Study chair
• Hubert TAUPE, PharmD, Study director, ISOCLIN