Defining the Functional Role of Iron in Aerobic Training and Physical Performance

Background: Despite the overall improvements in malnutrition in the Chinese population, iron deficiency (ID) and iron deficiency anemia (low iron and low hemoglobin, IDA) are still widely prevalent in China. According to recent studies, the prevalence of anemia in Chinese women of childbearing age is 20% and can be as high as 30% in rural areas, with 85% of anemia cases resulting from ID. Diabetes, heart disease, and obesity are also highly prevalent in China - though the Chinese government is taking actions against these epidemics, often via interventions promoting physical activity. Iron deficiency without anemia (IDNA) can impair adult physical performance and lowers time spent doing voluntary physical activities. However, iron supplementation intended to alleviate IDNA may be less effective in those who are physically active, suggesting an intricate, but currently undefined, relationship between iron status, exercise, and physical performance capacity. A combined analysis of iron status, exercise training, and physical performance in Chinese women could illuminate interactions between these factors and their role in diabetes and obesity reduction.

One common treatment for the symptoms of iron deficiency is the traditional Chinese herbal treatment, Ba-Zhen-Ke-Li (BZKL). While studies have shown that BZKL impacts expression of some iron-related proteins and increases endurance performance in rats, no studies have examined the efficacy of BZKL in improving iron markers or physical performance in humans. This study will compare the efficacy of BZKL in improving iron status and physical performance with that of ferrous sulfate supplementation.

Significance and Specific Aims:

The goal of the proposed research is to clarify the relationship between iron status, physical performance, and aerobic exercise training. By conducting an iron intervention study in combination with an exercise training program, the investigators can examine the modifying effect of iron status on the physical performance changes from aerobic exercise training as well as the modifying effect of participation in aerobic exercise in maintenance of iron status. To achieve this goal, a randomized double-blind, placebo controlled trial will be conducted with Chinese collegiate women.

The proposed work will be organized along three specific aims:

Aim I: To determine how changes in iron status, alone or in combination with exercise training, influence physical performance. Hypothesis: Subjects who both improve iron status and receive exercise training will show improvements in physical performance greater than the additive improvements resulting from either treatment alone. This result would suggest iron replete individuals benefit more from exercise training than those who are iron deficient.

Aim II: To determine how aerobic exercise training affects the maintenance of iron homeostasis. Hypothesis: Subjects participating in exercise training will show smaller improvements in iron status from iron supplementation than sedentary subjects who receive the same iron supplementation. This would suggest regular exercise training negatively impacts iron absorption, iron excretion and/or iron homeostasis.

Aim III: To determine whether BZKL can be used as an alternative to iron supplementation for improving iron status or physical performance of iron deficient, non-anemic women. Hypothesis: Those women who receive BZKL will improve in iron status and physical performance measures more than those who receive placebo.

The proposed research in Aims 1 and 2 is important because there is no known explanation for the observed relationships between iron, exercise training, and physical performance in IDNA. This research will allow clarification of the role that iron status plays in modifying the effects of exercise training on physical performance as well as whether participation in exercise impacts effectiveness of iron supplementation in improving iron status.

The long-term significance of this research is that establishing these relationships will further the current understanding of how iron status impacts and is impacted by aerobic exercise and physical performance. This knowledge could lead to improved physical activity interventions, which help reduce chronic diseases like obesity and diabetes in populations with high prevalence of ID, such as the U.S. and China. It will also help to inform iron interventions designed to alleviate ID in physically active populations, such as rural Chinese laborers and women in developed countries who participate in aerobic training to improve fitness.

Research Design and Methods:

Participants will be female subjects between the ages of 18-26 years with low body iron but normal hemoglobin (Hb) levels, (ferritin <20 μg/L and Hb > 120 g/L) who are otherwise healthy.

The study will be a randomized double-blind, placebo controlled trial with a 3x2 design. Power calculations were based on the pilot study performed by the investigators in Shanghai in 2013 and a study by Brownlie et al. Sample size was calculated to require 24 women per group, which was expanded to 29 subjects per group to allow for sample dropout. Subjects will be randomized to receive either 50mg of ferrous sulfate capsule twice a day (20mg elemental iron/day), 6 mg of BaZhen KeLi, or identical placebo capsules for 8 weeks. Half of each supplement group will also be randomly assigned to receive 8 weeks of aerobic exercise training (5 days/week, 25 minutes/day) or no training.

At weeks 0, 4, and 8 subjects will complete the following:

1. Anthropometric measurements (height, weight, skinfold thickness)
2. Physical activity and 4-day dietary intake questionnaires
3. Resting venous blood draw for iron status assessment
4. Exercise testing (VO2max test and energetic efficiency test)

To address Aims 1 and 2, the investigators will compare energetic efficiency, maximum ability to use oxygen, ventilatory threshold, and blood lactate concentrations at baseline, after supplementation (or placebo), and after exercise training (or no training). The 3x2 study design will allow for the determination of whether subjects receiving iron benefit more from exercise training. The investigators will also examine whether participating in exercise training affects iron homeostasis or lowers iron status.