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Anemia and Inflammation: A Research Dilemma

Student Blogger
By Sheela Sinharoy

How does one estimate the prevalence of anemia in a population? Historically, this has been a fairly straightforward matter of testing hemoglobin levels and comparing them to set cutoff figures. However, as we learn more about the physiological effects of infection and inflammation, the validity of our estimates is called into question.

Monday's symposium on the Biomarkers Reflecting Inflammation and Nutrition Determinants of Anemia (BRINDA) project highlighted some of these issues and potential approaches to address them. Parminder Suchdev of the Centers for Disease Control and Emory University began with an overview. He explained that the immune response triggers inflammation, which leads to temporarily decreased serum zinc and retinol and increased ferritin, transferrin receptor, and hepcidin. Although we know that these nutrients and biomarkers are affected by the inflammatory response, there is no widely accepted approach to effectively account for inflammation when analyzing and interpreting micronutrient data.

In order to address this gap, the BRINDA project team has been analyzing data from 15 countries representing all six WHO regions. Sorrel Namaste of Helen Keller International presented the key findings. Using C-reactive protein (CRP) and α-1 acid glycoprotein (AGP) as biomarkers of inflammation, they found that the prevalence of inflammation varied by country but was, on average, approximately 20% based on CRP and 40% based on AGP. Different methods of adjusting for CRP and AGP in the data analysis produced varying results, with a linear regression method being the most successful. These findings indicated that it is necessary to measure both CRP and AGP and to adjust for them in the analysis phase.

Next, Grant Aaron of Global Alliance for Improved Nutrition presented preliminary findings related to preschool aged children. In the sample, the burden of anemia was approximately 45%. Among children with anemia, 30% of the anemia was attributable to iron deficiency (unadjusted for inflammation). The age of the child, presence of inflammation, and anthropometric measures were associated with anemia in a majority of countries. Using an external correction factor, the proportion of anemia attributable to iron deficiency was adjusted to 35% for this age group.

Finally, Ken Brown of the Bill & Melinda Gates Foundation shared his interpretation of the findings. He emphasized the need for these biomarkers to establish the presence and magnitude of the problem, identify high risk sub-groups, and measure their response to interventions. This will require addressing practical challenges relating to specimen collection, analysis, and interpretation. He also pointed out that the need to collect biomarkers of any potential adverse effects of interventions. Ultimately, he encouraged the BRINDA team to make specific recommendations that other researchers can follow.

Overall, a major conclusion of the project thus far is that accounting for inflammation is necessary in order to improve the validity of anemia estimates. In acting on this conclusion, it will be important for researchers to ensure consistency in the parameters that are measured and to strengthen coordination between programs, evaluators and the academic community to build the evidence base.


Nutrition Notes Daily: Issue Three

Suzanne Price
The Tuesday issue of Nutrition Notes Daily is live, featuring research reporting advice, carotenoids, resistant starch, and a photo montage.

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Nutrition Notes Daily: Issue Two Is Live

Suzanne Price
Read the second issue for the latest news from ASN's Scientific Sessions & Annual Meeting. Don't miss the photos at the back!

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Nutritional Approaches for Osteosarcopenic Obesity: Interrelationships between Bone, Muscle and Fat

Student Blogger
By Teresa Johnson, MSPH, RD

A symposium chaired by Bahram Arjmandi, PhD, RD, and Carmen Castaneda-Sceppa, MD, PhD, provided insights into the etiology and pathophysiology of osteosarcopenic obesity, and presented suggestions for pharmacological and dietary treatment strategies.

Jasminka Ilich-Ernst, PhD, RD, a professor at Florida State University, outlined the problem and scope of osteosarcopenic obesity, a term first coined in 2012. Characterized by the coexistence of three distinct musculoskeletal disorders—osteopenia/osteoporosis, sarcopenia, and obesity—osteosarcopenic obesity is a complex condition, for which the proof-of-concept was established only recently.

A major concern with osteosarcopenic obesity, Ilich-Ernst said, lies in age-related fat redistribution and subsequent infiltration into bone and muscle. Typically bone, muscle, and fat progenitor cells differentiate in a balanced distribution to enable normal tissue development. But with aging, a sedentary lifestyle, poor nutrition, and low-grade inflammation, differentiation patterns become altered and fat production predominates.

Whereas current nutritional and lifestyle management recommendations address the individual components of osteosarcopenic obesity, they do not address the collective triad. Ilich-Ernst suggested adhering to current recommendations to achieve peak bone mass before age 30, gain and maintain adequate muscle mass, and maintain a health weight, but she added that increasing dietary protein to 25 percent of total energy and limiting carbohydrate consumption to approximately 40 percent of total energy might further reduce risk of developing osteosarcopenic obesity.

Further insights into the interconnected nature of bone, muscle, and fat were provided by Clifford J. Rosen, MD, a professor of medicine at Tufts University and research scientist at the Maine Medical Center Research Institute. Rosen explained that the three tissues derive from a single progenitor cell type, and their responses to various cytokines, hormones, and regulatory input, primarily the sympathetic nervous system, are similar.

He then described newly identified “beige,” or brown-like, adipocytes, which contain more mitochondria and are more thermogenic than classic white adipocytes. Beige adipocytes share a common progenitor cell with smooth muscle. As such, they can be viewed as a sort of  “hybrid” between fat and muscle cells. Intermittent cold exposure induces beige adipogenesis, a process referred to as “browning,” and promotes weight loss by increasing sympathetic tone—a potential non-pharmacological approach to body fat loss.

However, Rosen noted, whereas sympathetic tone enhances fat loss, it uncouples the process of bone remodeling, promoting bone loss. He added that many of the new classes of drugs that target beige adipogenesis might have similar, deleterious off-target effects on bone.
Ronenn Roubenoff, MD, MHS, of Novartis Institutes for Bone Research, and a professor of medicine and nutrition at Tufts University, compared the effects of dietary versus pharmacological approaches to treating sarcopenia. Sarcopenia, Roubenoff said, is an age-related loss of muscle mass due to type II muscle fiber atrophy. He said that preventing sarcopenia might increase life span and improve quality of life in older adults.

Although some research suggests increasing dietary protein intake might reduce muscle wasting, few data support changing current recommendations, Roubenoff said. In addition, the muscle-sparing effects of dietary protein differ in women versus men. Whereas women benefit from increased intake, men (who experience a U-shaped curve in response to intake) benefit from more moderate intake.

Roubenoff added that muscle, unlike other organs, doesn't senesce; rather, it remains plastic, providing the potential for older adults to regain muscle mass and function. However, muscle in older adults exhibits “anabolic resistance”—an inability to integrate and build muscle. Emerging pharmacological approaches target this resistance to reverse muscle wasting.

Finally, Wayne Campbell, PhD, a professor of nutrition science at Purdue University, described the differential effects of dietary protein intake during weight loss on bone, muscle, and fat. Specifically, Campbell addressed the question of how older adults can purposefully lose weight without compromising musculoskeletal function.

Campbell and his colleagues analyzed NHANES data from 1999-2004, a period that included dual energy X-ray absorptiometry data. They partitioned the data based on thresholds of the Recommended Dietary Allowance regarding bone health, and noted that whereas inadequate protein intake had an adverse effect on bone health in adults over age 50, high protein had variable effects. Campbell then described his research with whey supplementation and noted that groups that consumed higher amounts of a whey protein supplement lost more fat than groups consuming lesser amounts. However, they experienced no change in bone status, consistent with the epidemiological data.

At a minimum, Campbell said, adults should consume adequate protein. But he added that high dietary protein intake during weight loss has a positive effect on body composition, inducing greater fat loss while maintaining lean muscle mass. In addition, he noted that high protein intake has variable effects, depending on protein type. In particular, whereas protein from dairy and plant sources likely provides greater benefit to bone, protein from non-dairy animal sources likely benefits soft tissue.


Colorful carrots get a new use, producing tracers to study the brain

Student Blogger
By Ann Liu, PhD

Researchers are using carrots to produce a new tracer that will help scientists study vision and brain function. The results of this study were presented in the “Carotenoid and Retinoid Interactive Group: Bioavailability and Metabolism of Carotenoids and Vitamin A” on March 29 by Joshua Smith and John Erdman, PhD, from the University of Illinois at Urbana-Champaign.

Lutein is a carotenoid which accumulates in the retina of the eye and may protect the eyes from damage, especially age-related macular degeneration. It also accumulates in certain areas of the brain and may be beneficial for cognitive performance. However, little is known about how lutein accumulates in tissues such as the brain or how these tissues metabolize it. This led researchers to embark on a mission to develop lutein labeled with a non-radioactive, stable tracer (carbon-13) as a tool to study the metabolism of lutein in tissues.

Enter the colorful carrots. Carrots are a good source of lutein, but the amount of lutein can vary depending on the variety of carrot. Researchers tested seven different carrot cultivars that ranged in color from red to yellow to purple to see which one produced the most lutein. Then they had to culture the carrot cells in flasks and optimize the growing conditions to increase lutein production.

Once they figured out the optimal growing conditions, the carrot cells were fed carbon-13 labeled glucose. The lutein then had to be extracted using reverse-phase high performance liquid chromatography, and incorporation of the carbon-13 tracer was assessed using mass spectrometry. Approximately 58% of the lutein extracted from the carrot cells was uniformly labeled with carbon-13.

So what's next for this new tracer lutein? The researchers plan to use it to study tissue accumulation of lutein in animal models before embarking on any studies in humans. They will also be going back to the lab bench to see if there are any more changes they can make to further improve their lutein yield.

This research was funded by a grant from Abbott Nutrition through the Center for Nutrition, Learning, and Memory at the University of Illinois.


Developing the Evidence Base for Nutrition Recommendations

Suzanne Price
By Ann Liu, PhD

Systematic reviews are the basis for nutrition policy and guidance, but gaps in the evidence base can impact recommendations. Presenters at the symposium “Creating the Future of Evidence-Based Nutrition Recommendations, Using Lipid Research Case Studies” sponsored by ILSI North America spoke on various aspects that inform the process of developing dietary guidance and its implementation on Saturday, March 28. Major policy and regulatory groups such as the Dietary Guidelines for Americans Scientific Advisory Committee, American Heart Association, and the Institute of Medicine use systematic reviews as the basis for their decision making, but often the ability to make recommendations can be hampered by a lack of strong evidence.

The process of developing evidence-based reviews, such as the one used by the USDA Nutrition Evidence Library, must be rigorous, transparent, and minimize bias, because these reviews inform federal nutrition policy and programs. At the outset, key systematic review questions are developed which should reflect important decisional dilemmas in public health nutrition guidance.

The next critical step is deciding on inclusion and exclusion criteria, which determines what literature is included in the evidence base. Criteria that may be considered include study design, study duration, size of groups, drop out rates, and the health status of participants. This process is thoroughly documented and transparent so it can easily be determined why a study was included or excluded. The evidence base will go on to be evaluated by expert panels in order to make recommendations and guidances.

How can scientists ensure that their research is included in the evidence base?
  • When designing studies, it is important to consider the validity of the study design, the impact of endpoints, and the relevance and feasibility of interventions. Are the outcomes meaningful and are they translatable? If not, what additional information do you need? Researchers can also use the gaps in the literature identified in Nutrition Evidence Library systematic reviews to inform future investigations.
  • If studying chronic disease risk, use validated surrogate biomarkers.
  • Carefully consider your comparator group. One of the most common reasons studies are discounted from systematic reviews is they did not include appropriate control groups.
  • Once you are ready to report your results, follow established reporting standards such as the Consolidated Standards of Reporting Trials (CONSORT) for randomized clinical trials or the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines. This can help ensure that key information is included and is available for data abstraction in future systematic reviews and meta-analyses.
  • Participate in the process. Once draft reports such as the Dietary Guidelines for Americans Scientific Report are issued, there is the opportunity for public comment. Feedback from scientists with expertise is strongly encouraged.

Nutrition and Cognitive Outcomes

Suzanne Price
By Sheela Sinharoy

ASN's Scientific Sessions & Annual Meeting began on Saturday morning with a minisymposium on Nutrition and Cognitive and Neurological Outcomes. Researchers presented studies looking at a range of outcomes across the life course, from infants to the elderly.

Focusing on infants and preschool aged children, Sylvia Fernandez-Rao of the National Institutes of Health shared results from a randomized trial in India, in which participants received one of four interventions: micronutrient powders (MNPs), an early learning intervention, a combination of MNP + early learning, or neither. The results showed small improvements in some categories of development from both the MNP and early learning intervention but no evidence of additive effects.

Karim Bougma of McGill University presented results of a randomized trial of salt iodization in Ethiopia. The study enrolled children up to age five and distributed iodized salt in intervention communities. They found a significant difference between intervention and control areas in several measures of child development and also in maternal depression symptoms. This was true despite a significant increase in consumption of iodized salt in control areas as well as variable quality of salt iodization.

Moving on to older children, Beth Prado of UC-Davis presented results from a study that re-enrolled children ages 9-12 years whose mothers had received multiple micronutrient (MMN) supplementation while pregnant. They found that maternal MMN supplementation had small but significant positive effects on cognitive domains that were still measurable up to 12 years later. They additionally found that the cognitive benefits of MMN varied based on the mother's nutritional status.

Looking at young adults, Susan Emmett of Johns Hopkins University spoke about nutrition and hearing loss. She used data from the Nepal Nutrition Intervention Project, a randomized trial of preschool vitamin A supplementation that began in 1989. The project followed children and collected data every four months, including about any ear discharge in the previous week. Among children who had at least one episode of ear discharge, vitamin A supplementation was associated with a 42% risk reduction of young adult hearing loss.

Usha Ramakrishnan of Emory University also presented data on adults, specifically mothers. She described a randomized trial in Viet Nam, in which women received weekly pre-conceptional supplements of folic acid, iron-folic acid, or multiple micronutrients. The outcome of interest was maternal depression, but researchers found very few symptoms of postpartum depression, and there was no difference between treatment groups.

Finally, Alex Brito of UC-Davis spoke about a randomized trial of vitamin B12 in Chile, which measured neurophysiological outcomes among adults ages 70-79 years. The researchers found significant improvements in nerve conduction velocity with B12 intake but no improvements in other neurophysiological outcomes.

The minisymposium reflected just some of the diversity of interventions and outcomes within the very broad topic of nutrition and cognitive and neurological outcomes. It made clear that, as with many topics at EB 2015, this area is rich with future research opportunities, and there is still much to learn.


Issue One: Nutrition Notes Daily

Suzanne Price
The first issue of Nutrition Notes Daily at #ASNatExpBio features a thoughtful interview from incoming President Dr. Patrick Stover, coverage of maternal/fetal nutrition, awards, and osteosarcopenic obesity. Read the entire issue here or find copies throughout the Convention Center in Boston.

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Nutrition Notes Daily: Preview Issue

Suzanne Price
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Interview with Nancy Clark, MS, RD, ASN Media Award Winner

Suzanne Price
The ASN Nutrition Science Media Award is presented for consistent, accurate nutrition science reporting for a general audience over the last year. The 2015 recipient is Nancy Clark, MS, RD, an internationally-known sports nutritionist, weight coach, and nutrition author. She is a registered dietitian who specializes in nutrition for exercise, health, and the nutritional management of eating disorders and she is board-certified as a specialist in sports dietetics (CSSD).  Nancy will accept the award during ASN's Scientific Sessions & Annual Meeting on Sunday, March 29. In the linked interview she describes her career path and shares how she uses the dietary guidelines in her practice.