The Gamut of Sensory Nutrition Research at the Monell Center

In November 2019, at the brink of the COVID global pandemic, the National Institutes of Health convened a workshop called “Sensory Nutrition and Disease,” with the goal of challenging “multidisciplinary researchers working at the interface of sensory science, food science, psychology, neuroscience, nutrition, and health sciences to explore how chemosensation influences dietary choice and health.” The first three authors of the Workshop Report are Monellians: Danielle R. Reed, PhD; Amber L. Alhadeff, PhD; and Gary K. Beauchamp, PhD, and many of their co-authors are Monell collaborators or have worked at Monell at one point in their career.

In a post-pandemic world, and especially today – 2024 Anosmia Awareness Day – many people are more familiar with the  issues of smell loss. Now, we are seeing that sensory-nutrition-informed strategies designed for individuals with smell loss may help improve the flavor and liking of foods, as well as diet and overall well-being. In 2022, a few years into the pandemic, Monell researchers Stephanie R. Hunter, PhD and Pamela H. Dalton, PhD, MPH, made these connections in a review paper, illustrating the case for more sensory nutrition research for people experiencing smell loss, from any cause, including COVID.

The overall program of sensory nutrition research at the Monell Center spans quite literally from soup to nuts. In the past few months, Monell scientists have contributed many papers to the peer-reviewed literature of sensory nutrition from perspectives that span from molecular biology to that of policymaking. Sensory nutrition focuses on how the chemical senses – taste, smell, chemesthesis, and mouthfeel – influence health and well-being. Sound simple? Not quite. Looking deeper, we see how this field has broadened the areas to which it can be applied. Here are some quick takes on our latest contributions to this important field.

Drivers of What We Ingest

Eating behavior can be shaped by anything from cellular neuroscience to environmental factors. Every day, we decide what to ingest using sensory cues (like the taste and smell of food) as well as assessing nutritive value such as energy in food in the form of calories. What guides this “decision”? A multi-institutional team, including Monell researcher Amber Alhadeff, PhD, focused on AgRP-expressing neurons – critical drivers of feeding behavior – in a test of flavor-nutrient learning. In experiments using rodents, this is a Pavlovian process in which a flavor is used as a conditioned stimulus that becomes associated with ingested nutrients. The team stimulated AgRP neurons using optogenetics to control the activity of these cells during flavor-nutrient learning. The team found that continuous activity in AgRP neurons during flavor-nutrient learning enhanced the development of flavor preferences. The findings provide new insight into the role of AgRP neurons in assimilating sensory and nutritive signals in the development of food preference. Because we are constantly exposed to food-related cues that predict tasty and calorie-dense food, getting to the heart of this basic biological process may inform strategies to combat such chronic conditions as obesity and diabetes.

Downstream Influences

How food is processed can increase its safety, diversity, and accessibility. On the other hand, the easy availability of highly palatable and highly processed food is correlated with higher obesity rates worldwide. In a short-term experiment in mice, an international group, led by Luis Saraiva, PhD at Sidra Medicine, including Monell investigators Michael Tordoff, PhD, Johannes Reisert, PhD, and Julie Mennella, PhD, found that the short-term consumption of two highly processed diets, but not a grain-based diet, regardless of macronutrient content, adversely affected many aspects of physiology, including odor-guided behaviors, physiological responses to odorants, transcriptional profiles in the olfactory mucosa and brain regions, and brain glucose metabolism and mitochondrial respiration. These data have led the team to emphasize their concern that certain diets have the potential to alter food choices and influence the risk of developing metabolic disease.

Focus on the Youngest

Despite the importance of early nutrition, the 2017 recommendation by the European Food Safety Authority (EFSA) of an acceptable daily intake (ADI) of 30 mg glutamic acid/kg bw/day did not account for dietary intakes during infancy, namely the primary energy sources of human milk, infant formula, and solid foods, which can vary greatly in glutamic acid content. This spurred a team of researchers, led by Monell member Julie Mennella, PhD and Jillian Trabulsi PhD, RD at University of Delaware, and included  Alissa Smethers, PhD, RD, a Research Associate at Monell and Assistant Professor at Temple University, to determine daily intakes of the non-essential amino acid glutamic acid  over the first year.

The infants, who were part of a clinical trial, were randomized at two weeks of age to be fed either cow milk formula or a protein hydrolysate formula that had double the concentration of glutamic acid. They found that the type of formula mattered. Intakes of glutamic acid were significantly higher in infants fed the hydrolysate formula versus the cow milk formula. As glutamic acid intake from formula decreased, intake from other nutritional sources steadily increased from 5.5 months. When considering the overall diet, every infant exceeded the EFSA ADI of 30 mg glutamic acid/day. Given that the EFSA recommendation was not based on the intake of the primary energy sources during infancy, the present findings on the growing child’s ingestion of glutamic acid from infant formula and the complementary diet may be of interest when developing future guidelines and communications to parents, clinical care providers, and policy makers.

Mennella was also a member of the BEGIN (Breastmilk Ecology: Genesis of Infant Nutrition) Working Group, which was sponsored by the Pediatric Growth and Nutrition Branch of the Eunice Kennedy Shriver National Institute of Child Health and Human Development at the National Institutes of Health. The working group published a recent review article on the state of knowledge regarding the infant–human milk–lactating parent triad and how infants can achieve robust and healthy breastfeeding. The review highlighted the role of chemical senses in mother-infant interaction and identified research gaps.

Enhancing Umami

In another recent study, Monell investigator Paul Breslin, PhD, together with his graduate students and team from Rutgers University, wondered if molecules called ribonucleotides, which make up RNA and DNA, would increase taste sensitivity to glutamate when mixed. Glutamic acid (the acid form of glutamate), an amino acid used to form proteins, is a major metabolic fuel for cells of the intestinal lining, as well as other cell types. It is also a common type of neurotransmitter in the brain and well known to increase palatability when added to foods. The team measured both the taste sensitivity of monopotassium glutamate alone and with a background level of ribonucleotides. It turns out that the taste of glutamate is enhanced by adding a class of ribonucleotides called purines, including inosine, guanosine, and adenosine. Another class of ribonucleotides – the pyrimidines, including uridine and cytidine –  did not enhance the taste of glutamate, and cytidine inhibited glutamate taste for most people in their study. From this, they concluded that these building blocks modified glutamate taste, with purines enhancing sensitivity and pyrimidines negatively affecting sensitivity. Interestingly, pyrimidines increase in certain foods as they spoil and rot, such as seafood, and may inhibit glutamate taste to decrease the palatability of these potentially dangerous food states. Taste enhancement from the co-occurrence of glutamate and purines in the same food is meaningful as both are elevated in evolutionarily important sources of nutrition, such as insects and fermented foods, which are nutritious and probiotic components of human diets globally.

Work-arounds for Anosmia

People who lose their sense of smell tend to add more salt to their meals to improve their eating experience, but what could this excess sodium mean for their overall health? Are there any alternatives? Capsaicin, a chili pepper extract with a mild sting, may help increase salt taste intensity and lessen the need for adding too much salt. Monell postdoctoral fellow Stephanie Hunter, PhD, and faculty member Pamela Dalton, PhD, MPH found that capsaicin improved flavor, salt taste intensity, and eating enjoyment in study participants with smell loss. These results are helpful because adding capsaicin is one more tactic for people with smell loss to possibly better enjoy eating.

 Applying chemosensory science to dietary questions can help on many levels, from guiding nutritional policy recommendations to re-establishing a relationship with food in people who have lost their sense of smell. We hope researchers, policymakers, and patient groups, among many stakeholders, will find new allies on this Anosmia Awareness Day to keep the chemosensory research drums banging.

Featured image by Jill Wellington from Pixabay