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Does iron supplementation improve exercise performance in the absence of anemia?

Iron deficiency anemia and iron deficiency without anemia are the most common diet-related micronutrient deficiency disorders in the world.

These conditions can impact the oxygen-carrying capacity of red blood cells and iron’s role in oxidative energy production. As a result, those with impaired iron status often experience reduced work capacity. The effects of iron-deficiency anemia on exercise performance are fairly well understood. However, studies also suggest that individuals with depleted body-iron stores who do not have iron-deficiency anemia may also experience changes in physical performance. The impact of simultaneous iron supplementation and aerobic training, especially in untrained subjects, remains unclear. A study conducted by Laura Pompano and Jere Haas (Cornell University) examined the individual and combined effects of iron supplementation and aerobic training on endurance performance in women with iron depletion without clinical iron deficiency. The study results, published in the February 2019 issue of The Journal of Nutrition, show for the first time that iron supplementation improves endurance performance at near-maximal intensities in untrained women exhibiting iron deficiency without anemia.

A total of 73 sedentary, untrained women exhibiting depleted iron stores but without clinical iron-deficiency anemia were randomly assigned into 4 groups: aerobic training plus supplemental iron, aerobic training plus placebo, no training plus supplemental iron, and no training plus placebo. Subjects were given either a placebo or iron supplement (100 mg of ferrous sulfate), which were taken 2 times a day throughout the 8-week study period. Subjects in the aerobic training group were instructed to pedal 5 days a week on an exercise cycle at 60 revolutions per minute at 75% or 85% of their age-predicted maximum heart rate, with the difficulty increasing each week. Graded exercise tests were performed at baseline and at week 8, along with simultaneous oxygen consumption measurements. Iron status was also measured at baseline and at study completion.

The results of this study indicate that aerobic training, iron supplementation, and their combination all result in significant improvements in several measures of submaximal exercise performance.

The results of this study indicate that aerobic training, iron supplementation, and their combination all result in significant improvements in several measures of submaximal exercise performance. However, the effects of iron supplementation were of the same magnitude as those produced from aerobic training, with or without iron supplementation. In other words, improving iron status had no impact on maximal oxygen uptake, a measurement used to assess aerobic fitness, but it did improve endurance at near-maximal intensities. It remains unclear as to why there was no additive benefit of iron supplementation and training together. Nonetheless, this study provides a deeper understanding of the impact of iron status on aerobic fitness in both trained and untrained individuals.  Particularly noteworthy is that the study results suggest that when previously sedentary women exercise at an intensity near their personal maximum, improvements in endurance performance are associated with improved iron status.

Reference Pompano LM, Haas JD. Increasing Iron Status through Dietary Supplementation in Iron-Depleted, Sedentary Women Increases Endurance Performance at Both Near-Maximal and Submaximal Exercise Intensities. Journal of Nutrition. 2019; 109. In Press. https://doi.org/10.1093/jn/nxy271

Hennigar SR. Ironing out the Relation between Iron Supplementation and Exercise Performance in the Absence of Anemia.  Journal of Nutrition. 2019; 109. In Press. https://doi.org/10.1093/jn/nxy288

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New Focus on Reducing Anemia in Adolescent Girls

By Marion Roche, PhD

The target set out by the World Health Assembly is to reduce the anemia in all women of reproductive age by 50% by 2025. Women make up about 3.5 billion in population on our planet. In order to reach this World Health Assembly target, it will be essential to address anemia in the 600 million adolescent girls in the world and recently their nutrition has been getting more attention.

The global birth rate has declined over the past decade, except when analyzing the rate for adolescent girls, with 17-20 million adolescent pregnancies per year. Eleven percent of all pregnancies are to adolescents and 95% of these adolescent pregnancies are occurring in developing countries.

Complications from pregnancy and child birth are the second greatest contributor to mortality for girls 15-19 years of age. Young maternal age increases the risk for anemia during pregnancy, yet adolescent women are less likely to be covered by health services, including micronutrient supplementation, than older women. Compared with older mothers, pregnancy during adolescence is associated with a 50% increased risk of stillbirths and neonatal deaths, and greater risk of preterm birth, low birth weight and small for gestational age (SGA) (Bhutta et al, 2013; Kozuki et al, 2013; Gibbs et al, 2012).

Reducing anemia in adolescents is often motivated by efforts to improve maternal and newborn health outcomes for pregnant adolescents; however, benefits for improving adolescent school performance and productivity at work and in their personal lives should also be valued.

Globally, iron deficiency anaemia is the third most important cause of lost disability adjusted life years (DALYs) in adolescents worldwide at 3%, behind alcohol and unsafe sex (Sawyer et al, 2012).

Adolescents have among the highest energy needs in their diets, yet in developing countries many of them struggle to meet their micronutrient needs. The World Health Organization recommends intermittent or weekly Iron Folic Acid Supplements for non-pregnant women of reproductive age, including adolescent girls. IFA supplementation programs have often been designed to be delivered through the existing health systems, without specific strategies for reaching adolescent girls.

I have heard adolescence referred to as “the awkward years” when individuals explore self-expression and autonomy, but it is also definitely an awkward period for public health services in terms of delivering nutrition, as we often fail to reach this age group.

There have been examples of programs going beyond the health system to reach adolescent girls, such as through schools, peer outreach, factory settings where adolescents work in some countries and even sales in private pharmacies to target middle and upper income adolescent girls.
The Micronutrient Initiative implemented a pilot project with promising results in Chhattisgarh, India where teachers distributed the IFA supplements to 66,709 female students once per week during the school year over a 2 year pilot.

It was new for the schools to become involved in distribution of health commodities, but engaged teachers proved to be effective advocates. There were also efforts to reach the even more vulnerable out of school girls through the integrated child development centers, yet this proved to be a more challenging group of adolescents to reach. Peer to peer outreach by the school girls offered a potential strategy. The current project is being scaled up to reach over 3.5 million school girls.

Adolescent girls have much to offer to their friends, families and communities beyond being potential future mothers. It is time to get them the nutrients they need to thrive in school, work and life.

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Immunometabolism: The Role of Iron in an Emerging Field

By Ann Liu, PhD

Historically, immunology and metabolism have been distinct disciplines. However in recent decades we have learned that metabolic diseases such as obesity and type 2 diabetes result in major changes in inflammation and the immune response. Conversely, it has also become clear that certain behaviors and properties of lymphocytes are regulated by internal metabolic processes. Thus the new field of immunometabolism has emerged to examine the crosstalk between immune and metabolic processes. Speakers at the symposium “Diet and Immunometabolism,” co-sponsored by the Nutritional Immunology and Obesity RIS, highlighted the role of nutrients and metabolites in inflammatory processes on March 31.

While we may traditionally think of iron’s role in anemia and fetal development, it is also required for proper immune function and adipogenesis. Elevated serum ferritin levels are associated with type 2 diabetes, gestational diabetes, and metabolic syndrome. Excess iron also induces lipolysis and insulin resistance. Dr. Alyssa Hasty from Vanderbilt University School of Medicine presented data from mouse models indicating that iron homeostasis is disrupted during obesity. Iron is traditionally stored in the liver, however during obesity it appears that iron levels decrease in the liver and increase in adipocytes.

These changes may be related to changes in macrophage populations, which are important mediators of adipose tissue inflammation. Hasty identified two distinct macrophage populations based on their iron content. Some macrophages have high iron content which allows them to be isolated using a magnet while others have low iron content. Lean animals have both types of macrophages. However obese animals have increased levels of macrophages with low iron content.

This indicates that iron levels are changing in both adipocyte and macrophage populations during obesity and suggests that the ability of macrophages to sequester iron may be impaired. Further study is needed to identify the mechanisms of crosstalk between macrophages and adipocytes and examine potential functional consequences.

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Highlights from the Micronutrient Forum in Africa

By Sheela S. Sinharoy, MPH

The 3rd Micronutrient Forum Global Conference took place from June 2-6, 2014 in Addis Ababa, Ethiopia, with approximately 1,000 attendees and more than 80 sessions. Some of my personal highlights were:

• Lindsay Allen’s talk on biomarkers for vitamin B12. Dr. Allen argued that depending on the biomarker used, vitamin B12 deficiency may be more prevalent than iron deficiency.
• Michael Fenech’s presentations on the exposome, especially the impact of nutrient deficiencies on the integrity of DNA. He has found that the DNA damage from folate deficiency is equivalent to the damage from 10 times the allowable annual exposure to ionizing radiation.
• Daniel Raiten and Bas Kremer’s talks on the importance of a systems biology perspective. It’s good to be reminded of the need for research on nutrient-nutrient interactions and the role of nutrient “clusters” within biological systems.

The most interesting session, however, was the plenary session on the risks and benefits of iron interventions. Many of us know that iron deficiency is the most common nutritional disorder in the world. It is a major cause of anemia but not always the dominant cause. We also know that the main anemia control strategy worldwide is iron supplementation. However, in cases of anemia that are caused by factors other than iron deficiency, iron supplementation can actually be harmful, exacerbating malaria and increasing pathogenic bacteria in the gut. How, then, to determine whether or not iron supplementation is appropriate?

One possible solution came from Sant-Rayn Pasricha, one of the speakers in the plenary, who presented research on the use of the hormone hepcidin to assess iron status. He and his co-authors found that measurement of plasma hepcidin concentrations is useful for detecting iron deficiency and is more sensitive than ferritin. It is also more practical than the current approach, which involves measurements of ferritin, soluble transferrin receptor, and C-reactive protein to assess iron status.

This is of major importance, especially for those of us who work in developing countries where anemia levels are high. In Dr. Pasricha’s sample of children in The Gambia and Tanzania, 61% had anemia, but only 13% had iron deficiency anemia. Under current recommendations, all of the anemic children would be given iron supplementation, even though most of them were not iron deficient. This is not only a poor use of resources but, more importantly, potentially hazardous.

Iron supplementation is normally guided by hemoglobin levels, which measure anemia but not iron deficiency. Is it time to replace hemoglobin testing with hepcidin testing? There is no low-cost assay for hepcidin, so this is not a practical solution in the field just yet. In the meanwhile, it is important to consider the risks of infection and iron overload that can follow from inappropriate supplementation.

The knowledge I obtained at Micronutrient Forum will undoubtedly enrich my work moving forward. As I continue to make my way through articles referenced in various presentations, I am already looking forward to the 4th Micronutrient Forum Global Conference, scheduled for 2016 in Mexico.

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