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Effects of antioxidants on bone turnover markers in 6° head-down tilt bed rest

Katharina Austermann1, Natalie Baecker1, Sara R. Zwart2, Scott M. Smith3 and Martina Heer1*
  • 1 Ernährungsphysiologie, Institut für Ernährungs- und Lebensmittelwissenschaften, Universität Bonn, Germany
  • 2 Department of Preventive Medicine and Community Health, The University of Texas Medical Branch at Galveston, United States
  • 3 Human Health and Performance Directorate, National Aeronautics and Space Administration, United States

Background: Inactivity during space flight and in ground-based analogs, such as 6° head-down tilt bed rest (HDBR), is associated with bone loss. This bone loss is mainly induced by decreased mechanical loading [1,2]. Immobilization is associated with an increase of oxidative stress [3,4], resulting from excessive formation of reactive oxygen species (ROS) or dysfunction of antioxidant defense systems [5]. Oxidative stress also leads to increased activity of bone resorption processes [5]. Thus, antioxidants like polyphenols, omega-3 fatty acids, vitamins, and micronutrients may mitigate the damaging effects of ROS on bone turnover [6,7]. Hypothesis: We hypothesized that antioxidant supplementation during 60-d HDBR would reduce bone resorption and increase bone formation compared to non-supplemented controls. Materials and Methods: A randomized, controlled, single-blind intervention study in a parallel design was conducted at the Institute for Space Medicine and Physiology, Toulouse, France with 20 healthy male volunteers (age 34 ± 8 y, weight 74 ± 6 kg). The study was implemented in two campaigns; each consisted of a 14-d adaptation, a 60-d HDBR, and a 14-d recovery phase. Ten volunteers participated in each campaign. In both campaigns, five volunteers were randomly allocated to the intervention group and five volunteers to the control group. In the intervention group volunteers received an antioxidant-cocktail, consisting of 741 mg polyphenols, 2.1 g omega-3 fatty acids, 168 mg vitamin E and 80 µg selenium. In the control group volunteers received no supplement. All volunteers received an individually tailored and strictly controlled diet. For the calculation of energy intake the resting metabolic rate of volunteers was measured. During adaptation- and recovery period a physical activity level of 1.5 was used for energy intake calculation. During HDBR a physical activity level of 1.2 was considered, because of reduced physical activity. Protein intake was between 1 and 1.2 g/kg body weight/d. Fat intake was estimated between 30-35 energy percent/d and remaining energy percent/d were consumed as carbohydrates. The protein intake was kept constant during the whole study period and the energy reduction during HDBR was achieved by reducing fat- and carbohydrate intake. To ensure an adequate micronutrient supply vitamins and minerals were kept constant during the whole study period, according to ESA bed rest standards, based on the dietary reference intakes (DRI) [8,9]. Serum calcium, parathyroid hormone (PTH), and bone formation marker aminoterminal propeptide of type I collagen (P1NP) were analyzed, along with urinary calcium and bone resorption marker C-telopeptide of type I collagen (CTX). Presented results comprise pre-bed rest values (baseline) and values at HDBR-d 60. Statistical analysis: Data presented are means ± standard deviation. The statistical analysis was performed with IBM SPSS statistics 25.0. Data was tested for normal distribution with Saphiro-Wilk test. For the analysis of an inner-group comparison paired t-test was performed for normal distributed data and Wilcoxon test for non-normal distributed data. The inter-group comparison was detected by an unpaired t-test for normal distributed data and Mann-Whitney-U test for non-normal distributed data. P< 0.05 was considered as significant. Results: For all parameters a significant time effect was observed. Urinary calcium excretion was increased at HDBR-d 60 compared to baseline (pre-bed rest) with an increase of 35 ± 20 % (P<0.001) for the intervention group and 32 ± 26 % (P=0.003) for the control group. Serum calcium increased in both groups (4 ± 3 % for intervention group, P=0.02; 3 ± 2% in control group, P=0.007). The decrease of PTH was significant for the intervention group only (-21 ± 13%, P=0.002 in intervention group vs. -12 ± 17% in control group, P=0.07). Serum P1NP was increased at HDBR-d 60 with +23 ± 22 % in the intervention group (P=0.012) and +16 ± 13 % in the control group (P=0.004). Urinary CTX increased in both groups at the end of bed rest: 77 ± 42 % in the intervention group (P<0.001) and 103 ± 89 % in the control group (P<0.001). For all parameters no antioxidant supplement effect was found. Discussion: Our preliminary results indicate that the applied antioxidant-cocktail did not affect calcium homeostasis, bone resorption- and -formation markers. Other human studies, however, showed positive results on bone turnover after consumption of antioxidant rich foods, such as dried plums [10], green tea [11] and soy products [12]. These findings might be attributed to differences in the type of antioxidant administration (extract vs. food). Other food compounds, such as lipids, proteins, vitamins, minerals and/or other polyphenols affect antioxidant bioavailability and therefore may affect their efficacy [13]. Apart from these food related factors, bioavailability also depends on internal factors such as gender, age and colonic microflora [14]. In the present study healthy male volunteers (age 34 ± 8 y) were included, whereas previous studies investigated the effects of antioxidants in postmenopausal women [10–12]. Thus, differences in gender and age may be another explanation for the contradicting results. Conclusion: The antioxidant supplement applied as a countermeasure in this study did not reduce the deleterious effects induced by 60 days of HDBR on bone turnover.

Acknowledgements

Funded by the DLR Space Program with allocation of funds from the Federal Ministry of Economy and Technology (BMWi) under the support code: 50WB1535, and in part by the European Space Agency (ESA), the Centre National d'Etudes Spatiales (CNES) and the Human Health Countermeasures Element of the NASA Human Research Program.

References

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Keywords: Antioxidants, Polyphenols, bone turnover, Bed Rest, Immobility

Conference: 39th ISGP Meeting & ESA Life Sciences Meeting, Noordwijk, Netherlands, 18 Jun - 22 Jun, 2018.

Presentation Type: Extended abstract

Topic: Bones and Muscles

Citation: Austermann K, Baecker N, Zwart SR, Smith SM and Heer M (2019). Effects of antioxidants on bone turnover markers in 6° head-down tilt bed rest. Front. Physiol. Conference Abstract: 39th ISGP Meeting & ESA Life Sciences Meeting. doi: 10.3389/conf.fphys.2018.26.00048

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Received: 02 Dec 2018; Published Online: 16 Jan 2019.

* Correspondence: Dr. Martina Heer, Ernährungsphysiologie, Institut für Ernährungs- und Lebensmittelwissenschaften, Universität Bonn, Bonn, North Rhine-Westphalia, Germany, drmheer@aol.com