Micronutrients, Macro Impact

At the interface of food, nutrition, and agriculture, Lindsay Allen’s research has been informing nutrition guidelines and policies around the world for decades.

By | June 1, 2017

LINDSAY ALLEN
Director, US Department of Agriculture (USDA) Agricultural Research Service (ARS) Western Human Nutrition Research Center (WHNRC) Research Professor, Department of Nutrition University of California, Davis
PHOTO BY MAYUMI ACOSTA PHOTOGRAPHY
Lindsay Allen landed in California from England in 1969, following her then partner, a graduate student at the University of California, Davis. She had received a bachelor’s degree in food science and nutrition two years earlier and then worked in a human nutrition lab at the University of Cambridge. Allen began working as a technician in the UC Davis food science lab of Frances Zeman, who suggested that she should pursue a PhD. “I never considered getting a PhD or having an academic career, because few people in the U.K. went to graduate school, which was incredibly specialized there,” says Allen, who now serves as the director of the US Department of Agriculture Agricultural Research Service’s (ARS) Western Human Nutrition Research Center in California.

Allen enjoyed the coursework and found that her academic background—a science-focused curriculum of chemistry, biology, and nutrition courses in high school and during university in England—had prepared her well for graduate school.

For her thesis, Allen worked with a rat model to understand how protein deficiency during pregnancy affected female animals and their offspring. “At the time, there was a lot of interest in protein deficiency as a major cause of human malnutrition,” she says. Compared to the progeny of control rats that were not deficient in protein intake during gestation, the progeny of deficient animals had permanent changes in their body composition and in kidney development, Allen found. She is quick to point out that our knowledge of malnutrition has evolved significantly since her early rat work: “I’m not sure how relevant that model was for humans because people are never just deficient in protein.” Still, the work was related to human research conducted later by British epidemiologist David Barker that culminated in his eponymous 1990 hypothesis proposing that pre- and postnatal undernutrition, low birth weight, or premature birth can contribute to the development of chronic disorders such as diabetes and coronary heart disease later in life.

“We are trying to figure out how and why different people respond differently to food interventions.”

Even before her graduate school days in Zeman’s lab, Allen had been asking questions about what constitutes malnutrition and undernutrition in people, and has continued to probe its causes and consequences for more than 30 years. Allen’s human nutrition work in the U.S. and internationally in countries such as Mexico, Guatemala, and Kenya has resulted in nutrition policy changes she herself helped to write.

Here, Allen talks about her working-class roots, her seminal human studies showing that deficiencies in vitamin B12 and other animal-sourced micronutrients are at the heart of many poor-quality diets around the world, and why research on human milk has been slow to develop.

ALLEN ACTS

Strong work-ethic roots. Allen was born and raised in Clevedon, Somerset, a town in southwestern England on the Bristol Channel. “I come from a lower-middle-class background. My great-grandfather and grandfather were bakers who had their own business. They worked night and day. I grew up exposed to rural, working-class England, for which I am very grateful. Those values and experiences have carried over to the rest of my life,” she says.

Seminal experiences. In 1964, she entered the University of Nottingham, about 150 miles northeast of her hometown. There, she chose to focus on agriculture, food science, and nutrition, which exposed her to many different areas of science. While at university she did everything from horticulture and working in potato fields to analyzing the nutritional composition of packaged foods on the shelves of stores in the U.K. “There were huge nutrient losses from the production processes. What the label said on the package was not what was in the box.”

Inspiring mentor. After graduating in 1967, Allen worked in dietitian Elsie Widdowson’s lab at the University of Cambridge. Widdowson, among the most famous female scientists in the U.K. at the time, had designed the diets for British troops during World War II and studied how wartime rationing affected health. “She did incredibly pioneering research and was just an amazing woman. She showed me what was possible and reinforced my interests in studying human nutrition,” says Allen. In Widdowson’s lab, Allen made her first foray into human nutrition research: she helped conduct studies on the composition of human breast milk from women in the U.K. to understand how to improve infant formulas.

Nutritious beginnings. After receiving a PhD from UC Davis in 1973, Allen did a postdoc in the nutrition department at the University of California, Berkeley. She found that higher dietary protein consumption caused increased calcium loss from the body. “I worked in a human research facility called ‘the penthouse.’ It was three rooms that could house six people. We had paid volunteers live there for four months at a time, and we’d feed them formula diets with exactly known nutritional composition. Since this was Berkeley in the 1970s, we would get really interesting people who were willing to live like that for four months!” Allen says.

ALLEN ADVANCES

Getting her feet wet. In 1974, Allen became an assistant professor at the University of Connecticut, where she began to do the human population studies she had always wanted to conduct. “The funding for human research studies was really hard to come by in those days,” she says.  She and her colleagues studied the effects of diet, stress, and cigarette smoking on pregnancy outcomes in that state, finding that maternal low weight gain and smoking independently resulted in negative effects on babies, including lower birth weight and impaired postnatal motor performance and reflexes. Then, in 1981, Allen began what she calls her “real career,” working with colleagues at the Salvador Zubirán National Institute of Nutrition in Mexico City on the Mexico Collaborative Research Project to study malnutrition in rural Mexico. “I had almost no field experience or any knowledge of Spanish at the time and was handed a multimillion-dollar project to manage,” says Allen. The work, which took about eight years and included a yearlong sabbatical in Mexico and many international collaborators, was the start of Allen’s research on the prevalence of specific micronutrient deficiencies, how populations were affected, and the design of interventions to prevent and treat those deficiencies.

Important hints. While in Mexico, Allen collaborated with Adolfo Chávez, who had initially found evidence of stunted growth and poor diet in rural parts of the country. “Our research together ended up being a really good base that led to our discovery that lack of micronutrients was the primary basis of malnutrition. The diets in most of Mexico at that time were very low in animal-source foods, and based primarily on maize, legumes, and pasta, but not rich in many micronutrients,” says Allen. She and her colleagues followed Mexican women and their children aged 18 to 30 months and 7 to 8 years. The many measurements included detailed food intake, growth, and body weight, among other factors. Despite prior theories that attributed stunted growth to low overall calorie or protein intake, better growth during early childhood correlated not with a diet high in calories or proteins, but rather with a diet richer in animal-origin food, Allen found. “In the 1970s, the theory was that growth stunting happened because children didn’t have enough food to eat. While this is true in some children, energy deficiency, we found, is not the main problem. If you don’t have enough energy you will gradually wither away and die, but what we were seeing was different,” says Allen.

Missing micronutrients. “Then serendipitously, we started measuring the micronutrients in the blood of the subjects we were following and discovered really low levels of vitamins B2, B12, A, and E, and minerals such as iron and zinc. That was one of the first clues that the real problem with low dietary quality was lack of these micronutrients,” says Allen. She and her colleagues were among the first to uncover that deficiencies in micronutrients were prevalent in rural Mexico. “For most people there, maize and beans were the staples, and there was not enough access to animal-sourced foods, which led to not enough B vitamins. Dietary quality was really strongly associated with almost every outcome we looked at, from infant growth to child cognitive function to school performance.”

Implementing change. Allen was particularly interested in deficiencies of vitamin B12, which is only found in animal products. In follow-up studies in other countries, including Kenya, Allen and her team of collaborators showed that  supplementation with milk or meat improved vitamin B12 levels in school-age children and that consumption of these foods improved cognitive function and growth in these children. Her research on micronutrient deficiencies affected policy changes implemented by the World Health Organization (WHO) and other international agency–led food-fortification projects. “About 90 countries now fortify wheat and rice flour with vitamins and minerals, and this is still an evolving process,” says Allen, who was one of the authors of the 2006 WHO Guidelines on Food Fortification with Micronutrients. “There is now an interest from the Food Fortification Initiative to add vitamin B12 to certain foods, and I think our research is partly responsible for creating that interest,” says Allen. 

ALLEN ACCOMPLISHES

Brain effects. In 1993, Allen moved her laboratory from Connecticut to UC Davis, and in 2004 became the director of the USDA’s ARS Western Human Nutrition Research Center. Following up on her earlier work on vitamin B12 deficiency work in women and children, Allen’s team recently found, in a population study in Chile, that vitamin B12 deficiency in the elderly results in less efficient nerve conduction due to poor myelination of peripheral nerves, and that supplementation with the vitamin can lead to neurological improvements.  “What I always wanted to do was to follow up supplementation with cutting-edge tracking methods to understand the changes that supplementation can have. This is exactly the kind of work we can do at the WHNRC. In the study in Chile, we looked at hundreds of metabolites before the vitamin B12 injections and then again four months later. That gave us clues that there were phospholipids in the blood that increased in response to vitamin B12 that we never would have known about, which make up a major percentage of the phospholipids in nerve tissue in the brain.  This agrees with the fact that vitamin B12 deficiency can result in severe neurological and cognitive problems and loss of brain and nerve tissue that are related to lack of myelination,” says Allen.

Pioneering methods. Allen’s lab has also developed a novel way to analyze the B vitamin content in human milk from a single small sample. Breast milk analyses have lagged behind, according to Allen, because of the risk of misinterpreting the results and concluding that women should not breastfeed exclusively. “There is clear evidence that women should exclusively breastfeed for the first six months. That is the best advice. So any studies that show some breast milk may not be high quality risk creating confusion.” The second reason is that because of the carbohydrates, fats, and proteins that form in the matrix of breast milk, it is more difficult to study than human serum using mass spectrometry. After assessing how well fortification and supplementation increases micronutrient content in breast milk, Allen is now working on a Bill & Melinda Gates Foundation–funded project to further develop analytical methods and to establish reference values for micronutrients in human milk (which do not currently exist) using examples from well-nourished infant-mother pairs in Banjul, The Gambia; Copenhagen; Rio de Janeiro; and Dhaka, Bangladesh. “The quality of the information used to set recommended micronutrient intakes for lactating women, infants, and children will improve greatly once we do this study. And it will be possible to define whether milk micronutrient concentrations in a population group are low such that the mother’s or infant’s intake needs to be improved,” says Allen.

Today’s nutrition models. “Our nutrition models now are based on diets that reflect how people actually eat. Current dietary guidelines are based primarily on published studies, but their metabolic effects are rarely tested in people. We do analyses based on a mixed menu for some weeks and in response to a single meal, and can rapidly detect changes in thousands of metabolites in the blood. This is part of nutritional phenotyping; we are trying to figure out how and why different people respond differently to food interventions. As part of the Agricultural Research Service, the research arm of the USDA, we do these interventions that can then lead to dietary recommendations for prevention of chronic disease and support of health.”

A global issue. “Micronutrient deficiency is a global issue. In the U.S., our flour is fortified with folic acid, which is turned into folate in the body, to reduce the risk of neural tube birth defects in women who are genetically prone to having offspring with this problem. Folate deficiency often tends to be more prevalent in higher-income countries such as the U.S., Canada, and Scandinavian countries because our diets don’t contain enough of the legumes and vegetables that are staple sources of folate in other countries. Milk is fortified with vitamin D in the U.S., and iron is also added to flour.”

It takes a village. “In all of our fieldwork, we always had great collaboration with the local investigators, and over time we built a terrific network of international graduate students and postdocs who are now leaders in their own countries. In all our international studies, the local researchers direct the field studies, not us. You cannot do international studies without local support.” 

Greatest Hits

  • Showed that a diet deficient in animal-sourced foods, rather than low calorie intake, is a cause of stunted growth and poor development in children
  • Among the first to uncover that deficiencies in vitamins and/or minerals are a major reason why consumption of poor-quality diets negatively affects pregnancy, lactation, and child growth and development
  • Among the first to uncover the high prevalence of vitamin B12 deficiency around the world and to identify the causes and consequences of the deficiency, leading to vitamin B12 food- fortification programs in developing countries
  • Established global guidelines for adding micronutrients to flour and other foods
  • Developed efficient methods for analyzing nutrient content in human breast milk that revealed low concentrations of milk micronutrients in mothers consuming low-quality diets

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Comments

Avatar of: James V. Kohl

James V. Kohl

Posts: 481

June 5, 2017

It is great to see the first half of food energy-dependent biophysically constrained pheromone-controlled RNA-mediated cell type differentiation presented succinctly.

When others read more about Matching Dietary Amino Acid Balance to the In Silico-Translated Exome Optimizes Growth and Reproduction without Cost to Lifespan, it will be easier to explain the costs of virus-driven energy theft in terms of the degradation of messenger RNA that links mutations to all pathology.

For example, a single amino acid substitution in the seasonal influenza virus could cause the suffering and premature death of millions whose dietary amino acid balance failed to protect them from the rapid change in virulence.

See: Substitutions Near the Receptor Binding Site Determine Major Antigenic Change During Influenza Virus Evolution  

The major antigenic changes of the influenza virus are primarily caused by a single amino acid near the receptor binding site.
 

 

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