Clinical trial NCT06038656: Exercise and Galactooligosaccharide Supplementation on Inflammation and Iron Absorption (FexerGOS)
Official title: Effects of Exercise and Acute and Chronic Galactooligosaccharide Supplementation on Inflammation and Iron Absorption in Female Athletes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Resistance Exercise
Keywords: Galacto-oligosaccharides
female athletes
iron absorption
inflammation
Lead sponsor: North-West University, South Africa
Sponsor class: OTHER
Collaborators: name: Swiss Federal Institute of Technology
name: King's College London
First posted: 2023-09-15
Enrollment: 22
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: Iron depletion is common in female athletes depending on the sports discipline. Endurance and resistance exercise can induce inflammation thereby reducing dietary iron absorption. Galacto-oligosaccharides (GOS) improved iron absorption in young healthy women and infants, and improved gut inflammation in iron-supplemented infants. A stable isotope study will be performed to investigate the effect exercise and acute and chronic GOS supplementation on inflammation and iron absorption in female athletes.

Detailed description: Iron depletion is common in athletes, particularly in females, reaching prevalence rates up to 70% depending on the sports discipline. As iron is essential for energy production and oxygen transport, a deficiency can impair performance, especially in endurance athletes. Iron deficiency in athletes may be caused by inadequate intake, but reduced iron absorption and increased losses also seem to play a role. Both endurance and resistance exercise at a high intensity, can induce inflammation resulting in a hepcidin response via interleukin-6 (IL-6) regulation. Hepcidin is the master regulator of systemic iron homeostasis, and a recent study in adult males showed that vigorous exercise decreases dietary iron absorption associated with increases in IL-6 and hepcidin. Iron losses induced by exercise have been attributed to several factors, including gastrointestinal bleeding associated with endothelial damage, haematuria, haemolysis, and increased sweating. Galacto-oligosaccharides (GOS) have been shown to acutely enhance iron absorption in young, healthy women. In Kenyan infants with a high infectious disease burden, chronic GOS administration improved iron absorption and mitigated the negative effects of iron supplementation on gut inflammation, likely mediated by its bifidogenic effect. Whether GOS has the potential of improving iron absorption has not been studied in athletes.

The study aims are to determine 1) the effects of a bout of resistance exercise at 70% 1 repetition maximum (RM) on inflammation, hepcidin and iron absorption in female team athletes; and 2) the effect of acute and chronic GOS supplementation on iron absorption in response to the exercise bout.

The trial will entail two series of three iron absorption conditions separated by six weeks of GOS supplementation (10 g/day). The study participants will be 22 female athletes recruited from the North-West University and Potchefstroom area, South Africa. At baseline, the first series of three iron absorption studies will be conducted, all measuring iron absorption from a supplement administered with labelled ferrous fumarate in the following conditions: 1) after a period of rest; 2) three hours after an acute resistance exercise bout; and 3) three hours after an acute resistance exercise bout, co-administered with GOS. Following this, participants will consume GOS daily for 6 weeks, followed by an identical series of iron absorption studies. Markers of systemic and gut inflammation, hepcidin, microflora composition and iron status indicators before and after the GOS intervention will be determined. In addition, erythrocyte iron incorporation will be determined after both series of isotope studies. Furthermore, the kinetics of isotope appearance, inflammatory markers, and hepcidin for 24 hours during each of the six iron absorption studies will be investigated.

The primary hypotheses are that fractional iron absorption from a supplemental dose of ferrous fumarate will be: 1) lower three hours post exercise than post resting period; 2) higher with co-administration of GOS than without, both before and after six-week GOS intervention; and 3) higher after six-week intervention with GOS compared to baseline.

The secondary hypotheses are: 1) acute exercise bout will result in increased inflammatory and hepcidin response before and after intervention with GOS but the intervention may mediate these two responses; 2) chronic GOS intervention will increase relative abundance of Bifidobacterium spp, reduce gut inflammation and improve gut integrity and gut health; 3) chronic GOS intervention will improve iron status.

Eligibility criteria: Inclusion Criteria:

1. Female athlete.
2. Train at least 6 hours per week at moderate to high intensity.
3. Having low to moderate iron stores.
4. Willingness to consume the study supplement GOS during the intervention period.
5. Willingness not to consume daily nutritional supplements containing \>20 mg iron and/or pre- or probiotics (excluding food and beverages containing live cultures such as yoghurt, raw milk and cheese) during the study.
6. Willingness to not take any iron-containing supplements two days before and during the iron absorption study days or vitamin C on the iron absorption study days.

Exclusion Criteria:

1. Haemoglobin \<11 g/dl.
2. Treated or self-reported chronic disease, malabsorptive or gastrointestinal disorders (e.g. irritable bowel syndrome, functional bloating).
3. Pregnancy or lactation.
4. Subjects who cannot be expected to comply with the study protocol.
5. Difficulty drawing blood due to poor quality veins.
6. Individuals that have a fear of needles or suffer from vaso-vagal episodes when exposed to blood.
7. Participants who plan to start or stop the use of contraceptives before or during study period.
8. Participants who are lactose intolerant.
9. Participants who donated blood in the past 4 months or plan to donate during the study period.
10. Participants who use chronic anti-inflammatory medication such as corticosteroids or non-steroidal anti-inflammatory medication (NSAIDS).

Primary outcomes:
measure: a. Fractional iron absorption (%)
timeFrame: Visit 8 (day 29) and 15 (day 92).
measure: b. Fractional iron absorption (%)
timeFrame: Visit 8 (day 29) and 15 (day 92).
measure: c. Fractional iron absorption (%)
timeFrame: Visit 8 (day 29) and 15 (day 92).
Secondary outcomes:
measure: Interleukin 6 (pg/mL)
timeFrame: Visits 2 (day 1), 3 (day 2), 4 (day 8), 5 (day 9), 6 (day 15), 7 (day 16), 9 (day 64), 10 (day 65), 11 (day 71), 12 (day 72), 13 (day 78) and 14 (day 79)
measure: C-reactive protein (mg/L)
timeFrame: Visits 2 (day 1), 4 (day 8), 6 (day 15), 9 (day 64), 11 (day 71) and 13 (day 78).
measure: Alpha-1-acid glycoprotein (g/L)
timeFrame: Visits 2 (day 1), 4 (day 8), 6 (day 15), 9 (day 64), 11 (day 71) and 13 (day 78).
measure: Hepcidin (ng/mL)
timeFrame: Visits 2 (day 1), 3 (day 2), 4 (day 8), 5 (day 9), 6 (day 15), 7 (day 16), 9 (day 64), 10 (day 65), 11 (day 71), 12 (day 72), 13 (day 78) and 14 (day 79)
measure: Lipid mediators (pg/µL )
timeFrame: Visits 2 (day 1), 3 (day 2), 4 (day 8), 5 (day 9), 6 (day 15), 7 (day 16), 9 (day 64), 10 (day 65), 11 (day 71), 12 (day 72), 13 (day 78) and 14 (day 79)
measure: Erythropoietin (mIU/mL)
timeFrame: Visits 2 (day 1), 4 (day 8), 6 (day 15), 9 (day 64), 11 (day 71) and 13 (day 78).
measure: Serum iron isotope (%)
timeFrame: Visits 2 (day 1), 3 (day 2), 4 (day 8), 5 (day 9), 6 (day 15), 7 (day 16), 9 (day 64), 10 (day 65), 11 (day 71), 12 (day 72), 13 (day 78) and 14 (day 79).
measure: Gut microbial composition
timeFrame: Visit 8 (day 29) and 15 (day 92).
measure: Faecal short chain fatty acids (µmol/g)
timeFrame: Visit 8 (day 29) and 15 (day 92).
measure: Faecal pH
timeFrame: Visit 8 (day 29) and 15 (day 92).
measure: Faecal calprotectin (µg/g)
timeFrame: Visit 8 (day 29) and 15 (day 92).
measure: Faecal zonulin (ng/mL)
timeFrame: Visit 8 (day 29) and 15 (day 92).
measure: Intestinal fatty acid-binding protein (pg/mL)
timeFrame: Screening, Visits 4 (day 8), 8 (day 29), 9 (day 64), 11 (day 71) and 15 (day 92).
measure: Haemoglobin (g/dL)
timeFrame: Screening,Visit 8 (day 29), 9 (day 64) and 15 (day 92).
measure: Ferritin (µg/L)
timeFrame: Screening, Visits 2 (day 1) and 9 (day 64).
measure: Soluble transferrin receptor (mg/L)
timeFrame: Screening, Visits 2 (day 1) and 9 (day 64).
measure: Retinol-binding protein 4 (µmol/L)
timeFrame: Screening, Visits 2 (day 1) and 9 (day 64).
measure: Thyroglobulin (µg/L)
timeFrame: Screening, Visits 2 (day 1) and 9 (day 64).
measure: Fibroblast growth factor 21 (pg/mL)
timeFrame: Screening,Visits 2 (day 1) and 9 (day 64).
measure: Insulin-like growth factor 1
timeFrame: Screening, Visits 2 (day 1) and 9 (day 64).
measure: Dietary intake
timeFrame: Screening, Visit 8 (day 29) and 15 (day 92).
measure: Method comparison in the measurement of RBP4 (µmol/L)
timeFrame: Screening
measure: Method comparison in the measurement of Ferritin (µg/L)
timeFrame: Screening
measure: Method comparison in the measurement of sTfR (mg/L)
timeFrame: Screening
measure: Method comparison in the measurement of CRP (mg/L)
timeFrame: Screening
measure: Method comparison in the measurement of AGP (g/L)
timeFrame: Screening
measure: Method comparison in the measurement of I-FABP (pg/mL)
timeFrame: Screening
measure: Method comparison in the measurement of Thyroglobulin (µg/L)
timeFrame: Screening
Other outcomes:
Locations:
city: Potchefstroom
country: South Africa
facility: Este Vorster Research Facility
state: North West
Study officials:
affiliation: ETH Zurich
name: Isabelle Herter-Aeberli
role: PRINCIPAL_INVESTIGATOR
affiliation: North-West University
name: Jesslee du Plessis
role: PRINCIPAL_INVESTIGATOR
References: