Nafisa Jadavji
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The role of maternal folic acid supplementation on offspring neurodevelopment

 

Folic acid is a B-vitamin and is well known for its role during early neurodevelopment. It promotes the closure of the neural tube in utero. The neural tube in the developing embryo is the first step to forming the brain and spinal cord. If the neural tube does not close, it can lead to neural tube defects (NTDs), such as spina bifida. Women of child bearing age are recommended to supplement their diet with 0.4 -1 mg of folic acid daily. Additionally, to reduce the number of NTDs mandatory folic acid fortification laws were put into place in 1998 in the US and Canada, as well as other countries around the world. In response to mandatory fortification, there has been a reduction in the number of NTDs in both Canada and the US.

Recently, maternal over supplementation of folic acid has raised some concerns.  Over supplementation is defined as ingesting over 1 mg of folic acid daily. There has been an increase in over supplementation of folic acid in the US and Canada where mandatory folic acid fortification laws are in place and supplement use is high. Epidemiological studies have reported that too much folic acid has been associated with increased risk of cancer. Interestingly, too much maternal folic acid intake has been associated with autism spectrum disorder, but the data is not clear as other studies have reported protective effects. Furthermore, too much maternal folic acid has been reported to change neurodevelopment in animals.

A recent published study investigated whether too much maternal folic acid is associated with changes in the neurodevelopment of offspring. Using a mouse model of maternal over supplementation of folic acid the authors report that male offspring from mothers that were fed high levels of folic acid had impaired memory and brain development.  The amount of folic acid in the diet of mothers was 20mg/kg to model over supplementation in humans. Animals from mothers with over supplementation of folic acid did not remember seeing a familiar object as well as control animals did. Furthermore, they had reduced levels of a neurotransmitter that is important in learning and memory called acetylcholine.

These are some of the first results showing how maternal over supplementation with folic acid may affect early neurodevelopment. We recently published an up-to-date review of how maternal over supplementation of folic acid impacts offspring neurodevelopment.  Our comprehensive analysis includes studies from human populations as well as basic science studies to understand how things in the brain as well as behaviors are changing when mothers are supplementing with too much folic acid.  More studies are required to understand the full impact of how maternal over supplementation affects offspring neurological development. As someone wise once said, everything in moderation.

 

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Annabel Biruete
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When calcium is not equal to bone health

Calcium is traditionally considered the bone-health nutrient. This is because 99% of calcium is contained within the bone, in which calcium creates a mineral complex with phosphate (hydroxyapatite), giving bone its characteristic strength and function. However, besides forming part of bone, calcium is also involved in other functions, such as muscle function, nerve transmission, intracellular signaling, and others.

Bone is a very dynamic organ in which the rate of formation and resorption (or destruction) is different throughout the lifespan. During childhood and adolescence, the rate of formation is higher than the rate of resorption, leading to maximum bone gain. In older adults these rates are switched, causing loss of bone. This bone loss may lead to osteopenia, osteoporosis, and an increased risk of bone fractures.

Is an increased intake of calcium associated with reduced risk of fractures?

As a way to prevent bone loss and fractures in middle-aged and older adults, there is usually a push from public health initiatives and healthcare professionals to increase the intake of calcium. However, an increased intake of calcium (dietary + supplements) may not necessarily lead to fewer fractures. Two of the most recent systematic reviews and meta-analyses showed that increasing dietary calcium and the supplementation of calcium (and vitamin D) did not reduce the risk of fractures. However, this remains controversial as a previous meta-analysis showed that the supplementation of calcium and vitamin D was associated with a 15% risk reduction in middle-aged and older adults (community-dwelling and institutionalized).

 The use of calcium supplements may lead to a higher risk of cardiovascular disease

The hypothesis is that an increased intake of calcium may lead to a positive calcium balance (intake lower than output in urine + feces), in the absence of increased bone formation. This positive calcium balance may lead to the calcification of tissues other than the bone, such as the vasculature, increasing the risk of cardiovascular disease. However, this association remains controversial. A sub-analysis of the Multi‐Ethnic Study of Atherosclerosis (MESA), showed that those that had higher dietary calcium intake (without supplements) had a lower risk of coronary artery calcification, while those that were taking supplements had a higher risk. However, the National Osteoporosis Foundation and the American Society for Preventive Cardiology suggested that calcium intake (diet + supplements) that does not exceed the tolerable upper level of intake of 2000 to 2500mg/d is not associated with cardiovascular outcomes, and should be considered safe.

Special caution of high intake of calcium in subjects with reduced kidney function

A high intake of calcium, particularly those that use calcium supplements, may represent a problem for those with reduced kidney function, as they may not be able to excrete the extra calcium. In a study by Hill and collaborators, a calcium intake of 2500mg (1000 mg through diet + 1500mg from calcium carbonate), compared with a dietary calcium intake of 1000mg, led to 500mg of calcium retention in patients with reduced kidney function. Similarly, Spiegel and collaborators compared a diet with 800mg vs. 2000mg of calcium in subjects with normal and reduced kidney function. In those on the 2000mg calcium diet, there was a positive calcium balance, which was more marked in those with reduced kidney function. With these results, a calcium intake higher than 800-1000mg (diet + supplements) should be avoided in those patients with a reduced kidney function to prevent calcifications of tissues other than the bone.

Should health care professionals recommend a high intake of calcium?

The current evidence, in middle-aged and older adults, does not seem to support high calcium intakes (above the tolerable upper level) for the prevention of fractures. Additionally, high calcium intakes achieved with the use of supplements may be associated with increased risk of cardiovascular disease. However, the use of supplements may be useful for patients that have low calcium intake. Finally, special attention should be taken in patients with reduced kidney function, as a high intake (diet + supplements) may lead to an increased risk of cardiovascular disease.

 

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Omega-3s: “The Triple Threat” or “The Dynamic Duo”?

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The popularity of the essential polyunsaturated omega-3 fatty acids (O3FA) is on the rise. In 2017, O3FA achieved a spot on the top 20 foods and ingredients list that Americans are adding to their diets (The Hartman Group). In addition, the global fish oil market is expected to reach a whopping 4.08 billion dollars in the next four years!  The proposed health benefits are likely the driving force behind the increasing demand.

Despite their booming popularity, a large percentage of adults are not meeting the O3FA recommended intake. There are three primary O3FAs with distinct characteristics: alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Although commonly grouped under the umbrella term O3FAs, are all O3FAs created equal?

Unique Characteristics of O3FAs

Omega-3 fatty acids cannot be sufficiently produced in the body earning them the title of “essential fatty acids.” The plant-derived omega-3, ALA, is the parent precursor to EPA and DHA. Unfortunately, the conversion rate in our bodies is very low.  It is important to realize that in the process of metabolizing ALA to EPA and DHA, a series of anti-inflammatory markers are produced (leukotrienes, prostaglandins and thromboxane). As these anti-inflammatory metabolites are beneficial, direct EPA and DHA consumption is needed to meet bodily requirements.

Independent and Complementary Health Benefits

The majority of current research focuses on the health benefits of marine fatty acids.  DHA and EPA consumption portray an array of shared and complementary benefits related to the treatment of cardiovascular disease, depression diabetes, sleep disorders and more. DHA is more significantly associated with decreases in resting heart rate, blood pressure and with improvements in cellular membrane health due to its additional double bond and longer carbon chain. Increased cellular levels of EPA have been shown to benefit coronary heart disease, hypertension and to decrease inflammation. EPA and DHA are both associated with reduced gene expression related to fatty acid metabolism, reduced inflammation and oxidative stress.

Specific supplementation of ALA is not consistently associated with cardiovascular health. Although plant-derived ALA can be easily substituted in for excess omega-6 fatty acids (O6FAs). Research has shown that by reducing the O3FA:O6FA ratio, you can decrease bodily inflammation, increase anti-inflammatory markers and more efficiently utilize EPA and DHA.

An ALA, EPA and DHA-Rich Diet

The 2015-2020 Dietary Guidelines for Americans recommends that healthy adults consume at least 8 ounces of a variety of non-fried fatty seafood per week. For EPA and DHA requirements, the American Heart Association recommends fatty marine sources containing 500 mg or more of EPA and DHA per 3oz cooked serving (e.g., salmon and tuna).   ALA is the most commonly consumed O3FA in the Western diet as it is found in plant-based foods (e.g., dark green leafy vegetables, walnuts, canola oil, flax seed). Unlike EPA and DHA, an Adequate Intake (AI) level is established at 1.6 g/day and 1.1 g/day for men and women respectively.

The Final Verdict 

The wide range of benefits stemming from marine O3FAs indicates the importance of regular consumption of fatty seafood and EPA and DHA-containing products.  The incorporation of plant-derived ALA may serve more importantly as a substitute for omega-6 fatty acids to reduce bodily inflammation, decrease the high O3FA:O6FA ratio typically observed in the Western diet, and to help elevate EPA and DHA levels in the body. EPA and DHA may be featured as the health promoting “dynamic duo,” but ALA is still invited to the party!

 

References

1.         Yanni Papanikolaou JB, Carroll Reider and Victor L Fulgoni. U.S. adults are not meeting recommended levels for fish and omega-3 fatty acid intake: results of an analysis using observational data from NHANES 2003–2008. Nutrition Journal 2014.

2.         Harris WS, Mozaffarian D, Lefevre M, Toner CD, Colombo J, Cunnane SC, Holden JM, Klurfeld DM, Morris MC, Whelan J. Towards establishing dietary reference intakes for eicosapentaenoic and docosahexaenoic acids. J Nutr 2009;139(4):804S-19S. doi: 10.3945/jn.108.101329.

3.         Frits A. J. Muskiet MRF, Anne Schaafsma, E. Rudy Boersma and Michael A. Crawford. Is Docosahexaenoic Acid (DHA) Essential? Lessons from DHA Status Regulation, Our Ancient Diet, Epidemiology and Randomized Controlled Trials. Journal of nutrition 2004;134.

4.         Mozaffarian D, Wu JH. (n-3) fatty acids and cardiovascular health: are effects of EPA and DHA shared or complementary? J Nutr 2012;142(3):614S-25S. doi: 10.3945/jn.111.149633.

5.         Bork CS, Veno SK, Lundbye-Christensen S, Jakobsen MU, Tjonneland A, Schmidt EB, Overvad K. Dietary Intake of Alpha-Linolenic Acid Is Not Appreciably Associated with the Risk of Ischemic Stroke among Middle-Aged Danish Men and Women. J Nutr 2018. doi: 10.1093/jn/nxy056.

6.         Evangeline Mantzioris MJJ, Robert A Gibson and Leslie G Cleland Differences exist in the relationships between dietary linoleic and alpha-linolenic acids and their respective long-chain metabolites. Am J Clin Nutr 1995;61:320-4.

7.         Agriculture. USDoHaHSaUSDo. 2015 – 2020 Dietary Guidelines for Americans. 8th Edition. December 2015.

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Rukshan Mehta

Vitamin D and Cancer Risk – A potential magic bullet?

Vitamin D, also known as cholecalciferol, plays an important role in bone health and muscle strength and is essential for the prevention of rickets (1). Cholesterol is a precursor of Vitamin D, which is endogenously produced in the body when ergosterol is exposed to UVB sunlight through the skin. It is also found in eggs, fatty fish and supplements (1).

A recent study by researchers in Japan found that higher levels of vitamin D may lower the risk of liver cancer. The study conducted by researchers at the Center for Public Health Sciences at the National Cancer Center in Tokyo suggests that people who suffer from low levels of Vitamin D may be at an increased risk for many different types of cancers; however the overall body of evidence is mixed (2,3).

This latest study was published in BMJ and explored biologically active forms of vitamin D in blood samples of over 30,000 middle-aged adults across Japan in the early 1990s. The follow-up for individuals was over a 16-year period. This analysis was based off a sample of 3301 participants who developed cancer during the study and 4044 randomly selected participants, of whom 450 developed cancer. The research team found higher levels of circulating vitamin D led to lower risk for cancers, overall, after controlling for age, sex, smoking status and family history of cancer. They also controlled for seasonal differences in circulating vitamin D. They did not find differences in the effect of vitamin D by sex; however, authors noted that participants in the lowest quartiles of vitamin D status had a 22% higher risk of cancer when compared to those in the highest quartiles. Additionally, they noted a 50% lower risk of liver cancers for those in the highest vitamin D group compared to the lowest, after adjusting for diet.

Vitamin D status was only measured at one point during follow-up, which serves as an important limitation. Additionally, inherent selection bias means that participants in the study may have been more health-conscious than the public at large. The number of rare cancer cases in the cohort was also small.

It is important to note that these latest findings apply primarily to Asian populations and higher levels of Vitamin D in these communities may lower risk for cancer; however, these findings cannot be translated across the board. It is important for those at risk of sun burns to avoid direct unprotected contact with the sun, which is a known risk factor for skin cancers. Additionally, lower levels of vitamin D may be an indication of poor health, overall (2,3).

Other health benefits of vitamin D have been seen in meta-analyses that have found a 31% reduction in falls among those supplemented with vitamin D. It also plays a role in improving the body’s response to infection among patients with cystic fibrosis (4). For populations in the US, vitamin D deficiency remains a problem in populations including African American communities, where according to the National Health and Nutrition Examination Survey (NHANES), 60% of people suffer from low levels (5,6). Through fortification of dairy products and supplementation, these numbers have reduced; however, greater attention including additional research is needed to reduce risk of deficiency, with added benefits to risk reduction for other health conditions, including cancers.

References:

  • Khazai, N., Judd, S.E. & Tangpricha, V. (2008). Calcium and vitamin D: skeletal and extraskeletal health. Current Rheumatology Reports, 10(2), 110-117.
  • Budhathoki, S., Hidaka, A., Yamaji, T., Swada, N., Tanaka-Mizuno, S., Kuchiba, A., Charvat, H., Goto, A., Kojima, S., Sudo, N., Shimazu, T., Sasazuki, S., Inoue, M., Tsugane, S., Inoue, M., Tsugane, S., & Iwasaki, M. (2018). Plasma 25-hydroxyvitamin D concentration and subsequent risk of total and site specific cancers in Japanese population: large case-cohort study within Japan Public Health Center-based Prospective Study cohort. The British Medical Journal, 2018, 360. http://www.bmj.com/content/360/bmj.k671
  • Davis, N. The Guardian, Nutrition. (2018) Retrieved from: https://www.theguardian.com/science/2018/mar/07/vitamin-d-may-offer-protection-against-cancers-study-says
  • Pincikova, T., Paquin-Proulx, D., Sandberg, J.K., Flodstrom-Tullberg, & M., Hjelte, L. (2017). Clinical impact of vitamin D treatment in cystic fibrosis: a pilot randomized controlled trial. European Journal of Clinical Nutrition, 71, 203-205.
  • Jain, R.B. (2016). Recent Vitamin D data from NHANES: Variability, trends, deficiency and sufficiency rates and assay compatibility issues. Journal of Advanced Nutrition and Human Metabolism, 2. http://www.smartscitech.com/index.php/JANHM/article/view/1208
  • Avenell, A., Mak, J.C., & O’Connell, D. (2014). Vitamin D and vitamin D analogues for preventing fractures in post-menopausal women and older men. Cochrane Database of Systematic Reviews, 14(4).
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Moving toward a holistic model of woman-centered antenatal care

By: Sheela Sinharoy, MPH

Sunday began with a symposium titled, Delivering Nutrition Interventions to Women during Pregnancy: Beyond Individual Interventions to Comprehensive Antenatal Guidelines and Care. A series of speakers made clear that as antenatal care (ANC) models continue to evolve, there is plenty of room for improvement to provide a positive pregnancy experience for women and their families.

ANC is not meeting its potential. This was the conclusion of the first speaker, Erica Phillips. She discussed the model of focused ANC (FANC) recommended by the World Health Organization (WHO), which involves 75-80 tasks for an intake visit and 60-65 tasks for each follow-up. She explained that following these recommendations would require an estimated 30-40 minutes for a first visit and 20 minutes for a follow-up. Even when recommended tasks are completed, quality of care may still be low. Ms. Phillips stated that “where FANC has been adopted, success has been limited.”

Still, ANC can be an effective platform for breastfeeding promotion, according to the next speaker, Mduduzi Mbuya. He presented a case study from the Sanitation, Hygiene, Infant Nutrition Efficacy (SHINE) trial in Zimbabwe. The country faces a critical shortage of health workers, with only 9.8 skilled health workers per 10,000 people (as compared to a ratio of 117:10,000 in the USA). SHINE therefore engaged community-based village health workers and found that the prevalence of exclusive breastfeeding at six months of age increased from 23% to 68%. Dr. Mbuya attributed this result primarily to strong fidelity of implementation by village health workers.

Micronutrient supplementation is another important component of ANC, and Kate Dickin spoke about a trial of calcium supplementation in Kenya and Ethiopia. There, researchers found that women were motivated and willing to take calcium supplements as recommended and that most women sustained their adherence to the supplements through the six-week study period and said they would continue through the end of their pregnancies. Dr. Dickin attributed this largely to the intervention’s behavior change communication strategy, which was based on extensive formative research and addressed context-specific motivators and barriers.

Next, Catharine Taylor spoke about the way forward and the need for integrated, women-centered models of care. She said that ANC models should take the local context into account; have all goods and personnel in same physical space; provide clear and consistent guidelines, training and supervision to health workers; provide demonstrations and encourage active engagement and discussion; provide incentives and support; and implement women-held records and integrated health registers. As examples, she described the Centering Pregnancy model and women’s support groups, which have shown promise in a number of developing country settings.

Finally, Rebecca Stoltzfus closed the session, emphasizing the need for more community-based evidence, especially looking at “packages of ANC that are contextually adapted to be delivered in the most effective ways.” Thus, symposium attendees walked away with a substantial research agenda for the strengthening of antenatal guidelines and care.

 

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The Folate Fortification Story – How we fixed one problem…but may have created another

By: Mary Scourboutakos

Neural tube defects are a type of birth defect—affecting the brain, spine or spinal cord—that result from suboptimal folate status.
Folate is a B vitamin that’s naturally found in legumes (like chickpeas, lentils, pinto and kidney beans), seeds, leafy greens (like spinach, collard greens and romaine lettuce) and other vegetables such as asparagus, brussels sprouts and broccoli.

The problem is, people don’t eat enough of these foods. As a result, for many years, pregnant women were at risk for folate deficiency and hence, neural tube defects.

Prenatal supplements were the original solution to this problem as one of their prime ingredients is folic acid, the synthetic form of folate. However, they’re not a fool proof solution because neural tube defects form within four weeks of conception, often before women know they’re pregnant, and thus, before they start taking their supplements.

As a result, in the late 1990s folic acid was mandatorily added to white flour and enriched grain products to ensure that pregnant women would get enough folate, irrespective of whether they take a supplement.

Problem solved? Sort of…

Back in the early 1990s when discussions regarding the addition of folic acid to the food supply were taking place, it was suggested that after fortification was implemented, the dose of folic acid in prenatal supplements should be revised to prevent excessive intakes. The new problem is…the doses were never revised.

Currently, marketed prenatal supplements usually contain 1000 micrograms of folic acid, which is the daily upper limit for folic acid. Meanwhile, it’s recommended that pregnant women should consume about 400 micrograms of folic acid per day for neural tube defect prevention.

With mandatory fortification, three-quarters of a cup of cereal can provide greater than 400 micrograms of folic acid. So if you add a prenatal supplement to a bowl of cereal at breakfast, some bread at lunch, and pasta for dinner, you’re consuming a lot of folic acid!

According to Dr. Deborah O’Connor, a Professor from the University of Toronto who has spent decades studying folate and infant health, this could be a problem. She explained that in animal models, it has been shown that folate can make changes to the genes that are transcribed during development. And while similar data have not been done on humans, she said “if you’re not getting any benefit from those high levels, it would be prudent to cut back given the current status…(because) if there’s no benefit, there’s only a risk.”

From a regulatory point-of-view, she says there’s nothing stopping the industry from changing the amount of folic acid in the supplements. She suggested that the industry’s reluctance to modify the dose in prenatal supplements is probably due to inertia and the fact that “with nutrition you’re always fighting against the more is better philosophy.”

In the meantime, what should women do? In their 2015 clinical practice guidelines, the Society of Obstetrics and Gynecologists recommended a multivitamin containing 400 to 1000 micrograms of folic acid. But currently, there are no prenatal vitamins available with less than 1000. Hence, Dr. O’Connor’s recommendation is “do not use the prenatal, just use a regular multi-vitamin and maybe add a little iron.” Furthermore, she added “care must be taken to ensure vitamin A intakes do not exceed 3,000 mcg retinol activity equivalents (RAE) or 10,000 IU during pregnancy.”

Alas, it’s a classic story, you try to fix one problem, but in doing so, you create another. Hopefully prenatal supplements will be adjusted soon, but in the meantime, prudent folic acid intakes are probably a good idea.

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Living the Mediterranean Lifestyle

By Emily Roberts

The Mediterranean Diet is based on the eating patterns in the Mediterranean region and focuses on fruits, vegetables, fish, whole grains and healthy fats (1).  A diet not invented, but discovered, is now recognized as one of the healthiest dietary patterns (2). UNESO defines it as “a social practice based on all the “savoir-faire”, knowledge, traditions ranging from the landscape to the table and covering the Mediterranean Basin, cultures, harvesting, fishing, conservation, processing, preparation, cooking and in particular the way we consume” (3). The Mediterranean region is considered the Mediterranean Basin that borders the Mediterranean Sea and includes parts of seven countries: France, Portugal, Italy, Spain, Greece, Malta and Cyprus (4). There have been foreseen health benefits of consuming this diet, classifying it as “heart healthy” due to its likelihood to reduce the risk for heart disease (5,6). Living on the southern coast of France, I not only experience the Mediterranean lifestyle, but I have the opportunity to consume a Mediterranean Diet.

The Discovery

The Mediterranean Diet was discovered to have particular health benefits by Ancel Keys of the University of Minnesota in the 1950’s. He happened upon this discovery while studying the health of poor populations in Southern Italy in comparison to the wealthy in New York. He found the Italian populations had lower levels of cholesterol and a low rate of coronary heart disease (1).

Typical Foods

The diet is full of fresh foods including fruits, vegetables, herbs, fish, olive oil, breads, nuts and pastas (1). There is a very low consumption of red meats, poultry, butter, refined grains and processed foods. The diet is rich in fiber, monounsaturated fats and polyunsaturated fats, antioxidant compounds, and essential vitamins and minerals; conversely, it is very low in saturated fats. Given the diet’s composition of nutrient dense foods, strong adherence to this diet is associated with improved nutritional adequacy (2).

The Benefits

A strong adherence to the Mediterranean Diet enhances the chances of improving your health status. It has been found to reduce the risk for mortality, especially due to cardiovascular disease (7). There have been many cohort studies conducted in the Mediterranean Basin often showing good adherence to the diet and resulting in reduced incidence for cardiovascular events (6). The benefits of the diet are likely to improve with physical activity as well, such as decreased blood levels of LDL (1).

My observations

During my time in the south of France I have noticed the influence the agriculture and natural resources of the Mediterranean Basin has on the cuisine. This area is rich in olive groves, offering a plentiful supply of fresh olive products. The sea offers fresh fish, shellfish and other seafood, while local markets sell fresh fruits and vegetables. Cattle farms are not as populous in this area, so the consumption of red meat and butter is not as high as other European regions (such as Northern France). However, considering I am still residing in France, pastries, baguettes, and of course cheese are a typical part of the French dietary meal pattern. This differentiates my diet somewhat from other Mediterranean regions. Thankfully, walking as a means of transport is very common if not necessary, offering an efficient form of daily exercise. Fresh and homemade are the two words that best describe home cooking near the Mediterranean.  While residing with a local French family, I ate many freshly prepared meals. Everything made from scratch from salad dressings to whole grain bread.

The Mediterranean Diet is not an effort, rather a daily practice for many Europeans. As Americans, we may recommend it as a diet intervention or integrate it into our own eating habits for health reasons. This diet is seen to be successful by offering significant health benefits. This encourages me to try various diets from around the world that could potentially provide various health benefits for Americans, as well as a taste of a new culture.

1.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3684452/

3.La DiÈte MÉditerranÉenne 2010. Candidature transnationale en vue de l’inscription sur la Liste ReprÉsentative du Patrimoine Culturel ImmatÉriel de l’HumanitÉ. Espagne / GrÈce / Italie/Maroc, Version Informations Additionnelles.
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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.

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Multiple Micronutrients Offer Multiple Possibilities for Pregnant Women and Newborns

By Marion L. Roche, PhD, Micronutrient Initiative

An estimated 42% of pregnant women are anemic. Anaemia in pregnancy is associated with increased mortality for mothers and infants, low birth weight in infants and increased risk of premature delivery. Iron Folic Acid (IFA) supplementation is recommended where anaemia is a public health concern. Many in the global nutrition research community have been anxiously awaiting the JiVitA-3 Randomized Trial in Bangladesh. This study has been looking at the comparative effectiveness of iron folic acid (IFA) supplements vs. multiple micronutrient supplements for pregnant women and one month postpartum.

This recent research in Bangladesh, which shows potential to reduce preterm births and low birth weight, holds promise for contributing to global reductions in neonatal mortality, although reductions in infant mortality were not found to be significant in this study. Low birth weight puts infants at risk of neonatal mortality and developmental consequences later in life. The risks of neonatal deaths for preemies and the critical importance of addressing preterm births has gained increasing recognition through the “Born too Soon” Global Action Report.

These results are exciting and will be balanced with the costs of transitioning from IFA to multiple micronutrients as countries decide how, when, and if to transition to “multis.” For many countries, the multiple micronutrients will be an added cost, and will come with substantial implications for procurement and supply management. They will also be a new product for many of the physicians, nurses, health workers and family members that have a role of supporting and encouraging pregnant women, and most importantly for pregnant women themselves.

Multiple micronutrient supplements will only have benefits if pregnant women have access to the supplements, receive them early enough in pregnancy to consume the recommended dose, and be supported, motivated and encouraged to consume the supplements daily. Global experiences with IFA supplementation would suggest that adherence has been one of the greatest challenges to behaviour change. Supporting adherence requires a reliable supply, encouraging counseling for pregnant women and improving a women’s access to IFA and related ante natal care services.

Nepal’s national iron intensification project is an example of a project that, for over eight years, was able to increase iron coverage from 23% to 80% and increase adherence of 90 tablets from 6% to 56%. This was largely achieved through the integration of a community based delivery system of female community health volunteers (FCHVs) who delivered the IFA supplements to women in their community and also encouraged them and restocked their IFA supply when needed. The FCHVs also received participatory training and provided practical advice on how to support and encourage women. Additional strategies will be needed to further increase adherence and maintain the motivation of the FCHVs.

As the global nutrition community reflects on the implications of the evidence from this new study, they will also be looking to learn from IFA programs and the successes and challenges. Whether IFA or multis are selected as part of the strategy for anemia reduction and improving maternal and newborn health, innovative approaches and replication of best practices and promising strategies for increasing adherence and coverage are needed to reduce maternal anaemia and benefit infants.

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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.

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