Nutrition and Cognitive Outcomes

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.


ACCN14: A Day of Micronutrients

By Sheela Sinharoy, Student Blogger

Living up to its name, the Advances & Controversies in Clinical Nutrition conference began with sessions exploring the many controversies and uncertainties around micronutrients. Some of the issues explored by speakers included potential cancer-preventive and cancer-promoting effects of micronutrients, as well as the challenges of micronutrient research. Ultimately, it seems, questions remain about all of these areas and more.

The evidence on micronutrients is often contradictory and confusing. For example, Dr. Joel Mason spoke about micronutrients such as folate, selenium, and vitamin E, each of which has been shown to be cancer-preventive in some trials and cancer-promoting in others. He explained that the effects of these and other micronutrients may follow a curve in which they are protective in amounts up to a maximal optimal dose, after which the effect plateaus and may even become detrimental. However, even if this is the case, the optimal dose of each micronutrient remains unclear.

Similarly, other speakers discussed dietary supplements and their relationship to all-cause mortality, cardiovascular disease, cancer, and neurological diseases. Dr. Eliseo Guallar discussed meta-analyses of dietary supplements and concluded that most supplements have no effect or, in the worst cases, actually cause harm. He explained that there is very little evidence on multivitamins, because most studies focus on individual supplements rather than on multivitamins.

A further complicating factor is that different populations have different nutrient needs. Addressing this issue, Dr. Johanna Dwyer exhorted the audience to “mind the gaps” in micronutrient intakes in the US population. For example, she shared data indicating that women ages 20-29 years old in the US have borderline insufficient intakes of iodine. This has serious implications given the importance of iodine during pregnancy for neurological development of the fetus. Thus, special recommendations on iodine may be needed for women in this age group. Other sub-populations at risk, according to Dr. Dwyer, may include exclusively breastfed infants and some elder populations, especially those with heart failure.

Of course, more research is needed to better understand the role of micronutrients and dietary supplements, especially in the prevention of age-related chronic disease. However, as pointed out by multiple speakers, both observational studies and randomized controlled trials (RCTs) are fraught with challenges. Observational studies have a large potential for bias, and the observable effects will be small. At the same time, RCTs are problematic because, unlike pharmaceutical trials, there is never a true placebo group when studying micronutrients. As Dr. Balz Frei pointed out, everyone has some level of the essential micronutrients; at best, researchers can plan to measure the baseline levels and use those as inclusion or exclusion criteria for the study.

The goal of nutrition research, at least for many of us, is to generate evidence that can be used to guide others – whether clinicians, policy makers, or other program implementers – in making informed decisions. However, the current evidence base on micronutrients does not lend itself to clear guidance. One suspects that this will remain an area of advances and controversies for quite some time.


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.