Melatonin Supplementation and Exercise Program in Breast Cancer Women

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).


Eligibility Criteria:
Inclusion Criteria:

* Study participants were women with a history of ductal carcinoma in situ, lobular carcinoma in situ, or stage 1 to 3 breast cancer (5 years or more since diagnosis), not currently receiving chemotherapy or hormone therapy, postmenopausal, and Eastern Cooperative Oncology Group (ECOG) score ≤ 1

Exclusion Criteria:

* women who had exercised regularly for at least 20 minutes once and at least twice a week in the 3 months before the study
* Stage IV breast cancer or systemic recurrences
* Known autoimmune diseases: systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and multiple sclerosis.
* Severe kidney disease
* Use of adjuvant hormonal therapy, oral estrogen or progesterone replacement therapy, luteinizing hormone-releasing hormone agonists currently or within the past 60 days
* 6-month ≥ post-chemotherapy
* Concomitant use of sleeping pills every night at bedtime
* Concomitant use of black cohosh, flaxseed, or soy in pill or supplement form
* Functional limitation using the Barthel scale (less than 100 = maximum score) and the Lawton-Brody scale (less than 8 = maximum value).
* Uncontrolled hypertension (\>180/100 mm Hg).
* Uncontrolled atrial or ventricular arrhythmias, dissecting aortic aneurysm, severe aortic stenosis, acute endocarditis/pericarditis
* Acute thromboembolic disease.
* Moderate/severe chronic obstructive pulmonary disease (COPD) with Bodex index C or D Recent bone fracture (last month).
* Any other circumstance that your doctor considers prevents physical activity.
* Neoadjuvant chemotherapy or radiotherapy
* Concomitant use of beta-blockers
* 6-month ≥ post-radiotherapy
* Concomitant use of postmenopausal hormone replacement therapy
* Use of any type of oral melatonin supplement in the past 30 days
* Acute/chronic heart failure with NYHA (New York Heart Association) score \>II
* Uncontrolled orthostatic hypotension
* Recent acute myocardial infarction (3 to 6 months) or unstable angina.
* Acute/chronic respiratory failure.
* Diabetes mellitus with acute decompensation or uncontrolled hypoglycemia
* History of dementia (suspected by the GP environment and diagnosed).
* Shift-work and night-work