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| Name | Class |
|---|---|
| Sanidad de Castilla y León | OTHER |
| Ministerio de Ciencia e Innovación, Spain | OTHER_GOV |
| Fundación General Universidad de Valladolid | OTHER |
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Introduction: Breast cancer (BC) remains the leading cause of cancer in women with nearly 1.4 million new cases worldwide annually and 27.000 in Spain. Increasingly effective oncology therapies, however, have numerous adverse effects such as muscle degeneration, fatigue, decreased physical function and aerobic capacity, and deteriorating quality of life. In this sense, physical activity (PA) seems to be an interesting non-pharmacological strategy to alleviate these serious complications and with potential benefits for women with BC. Melatonin (N-acetyl-5 methoxytryptamine) is an indolic compound present with pleiotropic bioactions that regulates the circadian rhythm, antioxidant, anti-inflammatory, immunostimulant, cardioprotective, antidiabetic, antiobesity, neuroprotective, and antiaging actions. Furthermore, in recent years, many studies have described the key role of melatonin in preventing and developing cancer. The general anticarcinogenic mechanisms include epigenetic control, cell proliferation modulation, cell cycle regulation, apoptosis induction, and telomerase inhibition. Melatonin also exerts antiestrogenic activity, which is particularly significant in hormone-dependent tumors, regulating the expression and transactivation of the estrogen receptor, and modulating the enzymes involved in the local synthesis of estrogens. Despite all the mentioned properties, the use of melatonin in daily clinical practice is very limited, and additional studies are needed to better establish the role of this hormone in oncological clinical applications against different types of cancer.
Objective: To analyze the effect of supplementation with 4 g/day of melatonin for 10 weeks on muscle damage (CK and LDH), hormonal responses (estradiol, testosterone, cortisol and testosterone/cortisol ratio), antioxidant capacity (BAP and d-ROMs), Exerkins (Irisin and Sestrin 2), physical performance (handgrip strength, RPE and SPPB), anthropometry (body mass, BMI and fat mass) and WHOQOL-BREF (physical and psychological health, social relationships and environment) in women over 60 years of age who have suffered breast cancer and who follow a physical training program.
Methods: A total of 20 female volunteers between 60 and 73 years old (age: 65.5±4.52 years, BMI: 25.83±2.67 and body fat percentage: 33.73±5.54) who followed a physical activity adapted to their age and abilities are the members. of this study. The volunteers were divided into two groups: placebo (CG; n = 10) and supplemented with 5 g/day of melatonin (GI; n = 10). Differtent test were performed muscle damage (CK, and LDH), hormonal responses (estradiol, testosterone, cortisol, and testosterone/cortisol ratio), antioxidant capacity (BAP and d-ROMs), Exerkins (Irisin and Sestrin 2), physical performance (Hand-grip strength, RPE and SPPB), anthropometrics (Body mass, BMI and fat mass), and WHOQOL-BREF (physical and psychological health, social relationships and environment) were analyzed at the beginning (T1) and at the end of the 10 weeks of intervention (T2).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Melatonin supplementation group | Experimental | 2 capsules distributed in a single daily oral intake at 9 p.m. or 30 minutes before bedtime, whichever came first, for 10 weeks. |
|
| Placebo supplementation group | Placebo Comparator | 2 capsules distributed in a single daily oral intake at 9 p.m. or 30 minutes before bedtime, whichever came first, for 10 weeks. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Melatonin 6 mg | Dietary Supplement | wo capsules per day; Each capsule includes 3mg Melatonin Nutrifoods® Laboratories, Barcelona, Spain) by the Magistral Formulation Laboratory of a Pharmacy (Soria, Spain), following the rules of the Royal Spanish Pharmacopoeia (Ministry of Health, Government of Spain). Melatonin has a technical data sheet that guarantees its composition and purity (Reference No.: DIE-134). |
| Measure | Description | Time Frame |
|---|---|---|
| Irisin | Exerkin secreted primarily by skeletal muscle in response to exercise | first day of study and after 60 days of supplementation (end of study) |
| Sestrin-2 | Exerkin a highly conserved stress-responsive protein, can be triggered by various noxious stimuli, such as hypoxia, DNA damage, oxidative stress, endoplasmic reticulum (ER) stress, and inflammation. | first day of study and after 60 days of supplementation (end of study) |
| Measure | Description | Time Frame |
|---|---|---|
| BAP | biological antioxidant potential (BAP) test to estimate antioxidant capacity by measuring the blood concentration of antioxidants | first day of study and after 60 days of supplementation (end of study) |
| d-ROMs |
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Inclusion Criteria:
Exclusion Criteria:
Older women who have suffered from breast cancer
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Diego Fernández Lázaro, Professor; PhD | Contact | +34 658073375 | diego.fernandez.lazaro@uva.es | |
| Cesar Ignacio Fernández Lázaro, Professor; PhD | Contact | +34 975129185 | fernandezlazaro@usal.es |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Faculty of Health Sciences, University of Valladolid Soria Campus | Recruiting | Soria | Soria | 42004 | Spain |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40625889 | Derived | Celorrio San Miguel AM, Cacharro LM, Santamaria G, Garrosa M, Celorrio San Miguel M, Roche E, Garrosa E, Fernandez-Lazaro D. Adjuvant melatonin therapy during exercise prescription in breast cancer survivors on physical and anthropometric parameters, quality of life, and hormonal response. A randomized controlled trial. Front Sports Act Living. 2025 Jun 23;7:1594733. doi: 10.3389/fspor.2025.1594733. eCollection 2025. |
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| ID | Term |
|---|---|
| D008550 | Melatonin |
| ID | Term |
|---|---|
| D014363 | Tryptamines |
| D007211 | Indoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
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Parallel group placebo-controlled randomized clinical trial
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Double (Investigator, Participants)
|
| Placebo | Other | Two capsules per day; Each capsule includes 100-mg maltodextrin capsules were used as a placebo to match the color and texture of the Melatonin tablets to ensure blinding. |
|
diacron reactive oxygen metabolites (d-ROMs) pro-oxidant state of a biological sample, measures hydroperoxides
| first day of study and after 60 days of supplementation (end of study) |
| World Health Organization Quality of Life - BREF (WHOQOL-BREF) | a self-report questionnaire which assesses 4 domains of quality of life (QOL): physical health, psychological health, social relationships, and environment | first day of study and after 60 days of supplementation (end of study) |
| Creatine kinase (CK) | CK is an enzyme expressed by various tissues and cell types; markers of muscle damage | first day of study and after 60 days of supplementation (end of study) |
| Lactate dehydrogenase (LDH) | LDH is a catalytic enzyme found in many tissues of the body;markers of muscle damage | first day of study and after 60 days of supplementation (end of study) |
| Cortisol | catabolic hormone released in response to stress | first day of study and after 60 days of supplementation (end of study) |
| Testosterone | anabolic hormone | first day of study and after 60 days of supplementation (end of study) |
| Estradiol | female sex hormone of the estrogen group. | first day of study and after 60 days of supplementation (end of study) |
| BMI | Body Mass Index (BMI) anthropometric parameter which is the relationship between a person's body mass and their height | first day of study and after 60 days of supplementation (end of study) |
| Fat Mass | Anthropometric parameter fat mass allows the estimation of overweight or obesity in humans | first day of study and after 60 days of supplementation (end of study) |
| Short Physical Performance Battery (SPPB) | Test evaluates three aspects of mobility measures balance, the second gait speed, and the third leg strength | first day of study and after 60 days of supplementation (end of study) |
| Hand-grip strength | Grip strength is a measure of muscular strength or the maximum force/tension generated by one's forearm muscles | first day of study and after 60 days of supplementation (end of study) |
| RPE-Borg 10 | RPE stands for Rating of Perceived Exertion. | first day of study and after 60 days of supplementation (end of study) |
| D006571 | Heterocyclic Compounds |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |