Clinical trial NCT02374619: Iron Supplementation and Eccentric Exercise
Official title: The Effect of Eccentric Exercise and Iron Supplementation on Blood Redox Status and Muscle Performance in Different Age Groups
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Muscle Damage
Oxidative Stress
Keywords: eccentric exercise
pro-oxidants
free radicals
adults
children
Lead sponsor: University of Thessaly
Sponsor class: OTHER
First posted: 2015-03-02
Enrollment: 28
Sex: MALE
Minimum age (years): 10
Maximum age (years): 45
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER

Brief summary: Iron supplementation is very common in athletes, probably due to its catalytic role on the oxygen transport and optimal function of oxidative enzymes and proteins during exercise.

Iron is also characterized as a potent pro-oxidant, as it can lead to increased production of reactive oxygen and nitrogen species (RONS) that are involved in critical biological processes, such as gene expression, signal transduction and enzyme activity. In exercise, low levels of RONS are essential for optimal force production, whereas excessive production of RONS can cause contractile dysfunction, resulting in muscle weakness and fatigue. On the other hand, RONS are involved in signaling pathways and up-regulation of the expression of several genes, and therefore, RONS can provoke favorable effects such as training adaptations.

The purpose of the present study is to investigate the effect of iron supplementation on redox status, muscle damage and muscle performance after an acute bout of a valid muscle damaging eccentric exercise model in adults and children.

Detailed description: Eccentric muscle work is an essential part of human daily activities, such as walking, and in particular, when walking downhill or descending stairs. It is also a component of almost all of the athletic actions. The most notable and well-described effect of eccentric exercise is the muscle damage that peaks one to three days after exercise and is accompanied by several hematological, biochemical and physiological responses. Excessive production of reactive oxygen and nitrogen species (RONS) has been reported as a result of eccentric exercise. The typical approach so far, was to provide antioxidants to minimize oxidative stress, yet the effectiveness of such an approach is still under debate. Earlier studies reported positive effects of antioxidant supplementation on muscle performance, muscle damage and redox status, whereas more recently, well-received studies pointed towards the negative impact of antioxidant supplementation.

Iron is an essential element for the completion of numerous important biological functions, and also for optimal exercise performance. It is a vital component for the formation of oxygen-transport and iron-storage proteins hemoglobin and myoglobin, and for the most favorable function of many oxidative enzymes that affect the intracellular metabolism. Therefore, iron supplementation is commonly used to avoid exercise-induced perturbations of iron homeostasis and maintain the required iron stores that are necessary to address exercise needs or enhance physical performance. Iron is also characterized as a potent pro-oxidant, as it can lead to increased production of reactive oxygen and nitrogen species (RONS) that are involved in critical biological processes, such as gene expression, signal transduction and enzyme activity. Nevertheless, the role of iron on modifying redox responses after eccentric exercise has not yet been examined.

In a double blind, randomized cross over study that will be conducted in two cycles, healthy men and boys will receive either the iron supplement (37mg of elemental iron per day for three weeks before and one week after the eccentric exercise) or the placebo.

Blood samples will be collected: a) in adults prior to, at the end of first supplementation period, 24, 48,72 and 96 hours following an acute bout of eccentric exercise (5 sets x 15 max reps), and b) in children prior to, at the end of first supplementation period and 72 hours following the same exercise protocol. Blood drawings will be repeated at the same time points during the second supplementation cycle.

The aims of the present research are to investigate:

* The effect of an acute bout of eccentric exercise on muscle performance, redox status, and iron status.
* The effect of three weeks of iron supplementation on muscle performance, redox status, and iron status.
* The effect of four weeks of iron supplementation on muscle damage, muscle performance, and redox status after an acute eccentric exercise bout.
* The effect of age on muscle damage, muscle performance and redox status after an acute eccentric exercise bout and iron supplementation.

Eligibility criteria: Inclusion Criteria:

* Physiological body mass index (BMI).
* Physiological health profile.
* Subject provides written informed consent.

Exclusion Criteria:

* Professional athlete.
* Consumed any nutritional supplement the last 3 months.
* Performed pure eccentric exercise the last 6 months.
* Non Caucasian.

Primary outcomes:
measure: Changes in Maximum isometric torque (N.m)
timeFrame: Before the beginning of iron supplementation (baseline) at the end of the first supplementation period (3 weeks: pre-eccentric exercise), immediately after the eccentric exercise, and 24 hours, 48 hours, 72 hours, 96 hours after the eccentric exercise
measure: Changes in Maximum concentric torque (N.m)
timeFrame: Before the beginning of iron supplementation (baseline) at the end of the first supplementation period (3 weeks: pre-eccentric exercise), immediately after the eccentric exercise, and 24 hours, 48 hours, 72 hours, 96 hours after the eccentric exercise
measure: Changes in Maximum eccentric torque (N.m)
timeFrame: Before the beginning of iron supplementation (baseline) at the end of the first supplementation period (3 weeks: pre-eccentric exercise), immediately after the eccentric exercise, and 24 hours, 48 hours, 72 hours, 96 hours after the eccentric exercise
measure: Changes in Range of motion, ROM (degrees)
timeFrame: Before the beginning of iron supplementation (baseline) at the end of the first supplementation period (3 weeks: pre-eccentric exercise), immediately after the eccentric exercise, and 24 hours, 48 hours, 72 hours, 96 hours after the eccentric exercise
measure: Changes in Delayed onset muscle soreness, DOMS (scale 1-10)
timeFrame: Before the beginning of iron supplementation (baseline) at the end of the first supplementation period (3 weeks: pre-eccentric exercise), immediately after the eccentric exercise, and 24 hours, 48 hours, 72 hours, 96 hours after the eccentric exercise
measure: Changes in Creatine kinase, CK (activity IU)
timeFrame: Before the beginning of iron supplementation (baseline), at the end of the first supplementation period (3 weeks: pre exercise), and 72h after the eccentric exercise
Secondary outcomes:
measure: Changes in Reduced glutathione, GSH (μmol/g Hb)
timeFrame: Adults: at baseline, pre-eccentric exercise, 24,48,72 & 96 hours after the eccentric exercise. Children: at baseline, pre-eccentric exercise and 72 hours after the eccentric exercise
measure: Changes in Oxidized glutathione, GSSG (μmol/g Hb)
timeFrame: Adults: at baseline, pre-eccentric exercise, 24,48,72 & 96 hours after the eccentric exercise. Children: at baseline, pre-eccentric exercise and 72 hours after the eccentric exercise
measure: Changes in Thiobarbituric acid-reactive substances, TBARS (μM)
timeFrame: Adults: at baseline, pre-eccentric exercise, 24,48,72 & 96 hours after the eccentric exercise. Children: at baseline, pre-eccentric exercise and 72 hours after the eccentric exercise
measure: Changes in Protein carbonyls, PC (nmol/mg pr)
timeFrame: Adults: at baseline, pre-eccentric exercise, 24,48,72 & 96 hours after the eccentric exercise. Children: at baseline, pre-eccentric exercise and 72 hours after the eccentric exercise
measure: Changes in Catalase (μmol/min/mg Hb)
timeFrame: Adults: at baseline, pre-eccentric exercise, 24,48,72 & 96 hours after the eccentric exercise. Children: at baseline, pre-eccentric exercise and 72 hours after the eccentric exercise
measure: Changes in Total antioxidant capacity, TAC (mm DPPH)
timeFrame: Adults: at baseline, pre-eccentric exercise, 24,48,72 & 96 hours after the eccentric exercise. Children: at baseline, pre-eccentric exercise and 72 hours after the eccentric exercise
measure: Changes in Uric acid (μm)
timeFrame: Adults: at baseline, pre-eccentric exercise, 24,48,72 & 96 hours after the eccentric exercise. Children: at baseline, pre-eccentric exercise and 72 hours after the eccentric exercise
measure: Changes in Bilirubin (μM)
timeFrame: Adults: at baseline, pre-eccentric exercise, 24,48,72 & 96 hours after the eccentric exercise. Children: at baseline, pre-eccentric exercise and 72 hours after the eccentric exercise
measure: Changes in Iron concentration (mg/dL)
timeFrame: Adults: at baseline, pre-eccentric exercise, 24,48,72 & 96 hours after the eccentric exercise. Children: at baseline, pre-eccentric exercise and 72 hours after the eccentric exercise
measure: Changes in Total Iron Binding Capacity (TIBC) (μmol/L)
timeFrame: Adults: at baseline, pre-eccentric exercise, 24,48,72 & 96 hours after the eccentric exercise. Children: at baseline, pre-eccentric exercise and 72 hours after the eccentric exercise
measure: Changes in Transferin saturation (TS) (%)
timeFrame: Adults: at baseline, pre-eccentric exercise, 24,48,72 & 96 hours after the eccentric exercise. Children: at baseline, pre-eccentric exercise and 72 hours after the eccentric exercise
measure: Changes in Ferritin (ng/mL)
timeFrame: Adults: at baseline, pre-eccentric exercise, 24,48,72 & 96 hours after the eccentric exercise. Children: at baseline, pre-eccentric exercise and 72 hours after the eccentric exercise
Other outcomes:
Locations:
Study officials:
affiliation: University of Thessaly
name: Athanasios Z Jamurtas, Dr
role: STUDY_CHAIR
References:
citation: Theodorou AA, Nikolaidis MG, Paschalis V, Koutsias S, Panayiotou G, Fatouros IG, Koutedakis Y, Jamurtas AZ. No effect of antioxidant supplementation on muscle performance and blood redox status adaptations to eccentric training. Am J Clin Nutr. 2011 Jun;93(6):1373-83. doi: 10.3945/ajcn.110.009266. Epub 2011 Apr 20.
citation: Gomez-Cabrera MC, Martinez A, Santangelo G, Pallardo FV, Sastre J, Vina J. Oxidative stress in marathon runners: interest of antioxidant supplementation. Br J Nutr. 2006 Aug;96 Suppl 1:S31-3. doi: 10.1079/bjn20061696.
citation: Deli CK, Fatouros IG, Paschalis V, Tsiokanos A, Georgakouli K, Zalavras A, Avloniti A, Koutedakis Y, Jamurtas AZ. Iron Supplementation Effects on Redox Status following Aseptic Skeletal Muscle Trauma in Adults and Children. Oxid Med Cell Longev. 2017;2017:4120421. doi: 10.1155/2017/4120421. Epub 2017 Jan 22.