Iron Deficiency Without Anemia Clinical Trial
Official title:
Defining the Functional and Metabolic Role of Iron in Aerobic Training and Physical Performance
Iron deficiency is known to negatively impact physical performance, attention, and time
spent doing physical activity. As a result, an iron deficient person must expend more energy
to complete the same amount of work as someone who is healthy. Another interesting
relationship has been observed between exercise training and iron status in that women who
participate in exercise training often have higher rates of iron deficiency than sedentary
women. ID is commonly treated using daily iron supplementation. However, it is currently
unknown whether participating in regular exercise somehow impacts the effectiveness of iron
supplementation. Iron deficient women who participate in exercise programs may potentially
benefit less from iron supplementation than those who do not. Another 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. The Cornell research team will achieve these objectives in
collaboration with colleagues at Kunming Medical University (KMU) in Kunming, China. A
double-blind, randomized, placebo controlled study will be conducted by a Cornell graduate
student at KMU. The subjects will be healthy women, age 18-26 years, attending KMU. Blood
samples will be collected and analyzed for measures of iron).
Subjects will be randomly assigned to receive 50 mg of ferrous sulfate (10 mg of elemental
iron), 6mg of BZKL, or an identical placebo pill twice daily for 8 weeks. Subjects will be
further randomly sub-divided to receive aerobic exercise training or no training during the
8-week supplementation period. At weeks 4 and 8, subjects will perform the same series of
tests as was performed at baseline. The investigators hypothesize that: 1. the women who
train and received iron will have smaller improvements in iron status than those who do not
train 2. The women who receive iron and train will have greater improvements in physical
performance than those who train and do not receive iron, and 3. The women who receive BZKL
will improve their iron status or physical performance more than those who receive placebo.
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.
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Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Factorial Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Basic Science