Julie A. Mennella

Acesulfame potassium (Ace-K) is a low-calorie sweetener (LCS) widely used as an ingredient in foods and beverages and an excipient in pediatric medicines. While prior candidate gene studies have established that genetic variants in bitter taste receptor (TAS2R) genes are associated with variation in the taste of Ace-K, we sought to identify genetic contributions to its taste using a genome-wide association study (GWAS) of 141 adult panelists who rated the taste of an aqueous solution of Ace-K using the general labelled magnitude scale (gLMS) and its palatability using the hedonic gLMS. To determine whether GWAS-identified associations with Ace-K generalized to a more complex stimulus, panelists also rated the taste of a pediatric medicine that contains Ace-K as an excipient (Children’s Motrin™). We identified that a TAS2R-containing locus on chromosome 12 was associated with bitterness ratings of Ace-K (p-values < 5 × 10^− 8), and the lead SNP rs2708381 in this locus was associated with the sweetness intensity of Children’s Motrin™ (p-value = 0.001). SNP rs2708381 was also associated with perceived intensity ratings of another LCS, neohesperidine dihydrochalcone, in a replication GWAS of 1,757 panelists (p-value = 0.002). A locus within the gene ELMO1, which encodes engulfment and cell motility protein 1, was associated with hedonic ratings of Ace-K (p-values < 5 × 10^− 8), and no genome-wide significant signals were observed for sweetness ratings. These findings identify a novel genetic locus containing TAS2R genes that contributes to personal differences in the taste of Ace-K, which may impact the acceptance of medicines, food, and beverages containing Ace-K. Clinical trials registration: Sensory evaluation of the taste of pediatric medicines (MEDTASTE); clinical trials registry number NCT03627351, registered on 13 August 2018.

Background:: Flavor, a complex sensation mediated by the chemical senses of taste, smell, and chemesthesis, is a primary driver of food acceptance. Because what we eat is an important influence on health in modern societies, we need to understand what shapes the acceptance of foods from an early age. Summary:: As infants transition from an all-milk diet to one that contains complementary foods of varying flavors and textures, biological factors interact with early experiences in shaping the acceptance or rejection of these complementary foods. Children are naturally drawn to foods that taste sweet or salty. However, repeated exposures to more complex flavors, transmitted from the mother’s diet to amniotic fluid and to human milk, and inherent in infant formulas and complementary foods (with 8–10 exposures or more), familiarize and facilitate children’s acceptance of the varying sensory properties of foods. Family members modeling eating these foods also encourage acceptance in children. Such functional plasticity, one of the main characteristics of the brain, highlights the ability to change behavior based on experience.

Millions of people in the United States experience a reduced or distorted ability to smell or taste. Chemosensory disorders such as anosmia (the inability to smell), parosmia (distorted smell), or dysgeusia (altered taste) have major impacts on health and quality of life including difficulty sensing dangers such as fire or spoilage, a diminished palatability of food and drink that can negatively influence diet and nutrition, feelings of social isolation, and an increased incidence of frailty, anxiety, and depression. Smell or taste dysfunction can also be symptoms of other health issues, including sinonasal disease, cancer, or neurodegenerative disease. Aging adults are disproportionately affected. However, smell and taste function are not regularly assessed as a part of routine healthcare despite their prevalence and impact. This is a lost opportunity, as early detection of a chemosensory disorder would enable patients to obtain needed validation, education and support for their health challenge, could direct both patient and provider to treatment options, and may suggest underlying health issues that should be addressed. To better understand the current barriers to including chemosensory testing as a regular component of health care and to identify opportunities to overcome those barriers, the conference “Towards Universal Chemosensory Testing” was convened on November 5–7, 2023, in Philadelphia, PA. This conference brought together scientists, clinicians, patients, and other experts to discuss these issues and identify collective ways to overcome barriers to testing. This white paper—which is focused primarily on the US healthcare system—is the result of those discussions.

Olfactory dysfunction resulting from COVID-19 has imparted a lasting impact on olfaction among the general public, including pregnant women contracting SARS-CoV-2 infection. While olfactory dysfunction can impact physical, mental, and psychosocial well-being, there has been little research on olfaction during pregnancy and postpartum, nor the impact of SARS-CoV-2 infection on olfaction while pregnant. Therefore, the primary study aims are to evaluate olfaction in the postpartum period and determine the impact of antecedent SARS-CoV-2 infection. We recruited two cohorts of postpartum women, those with a history of SARS-CoV-2 infection before or during pregnancy (COVID cohort; n = 109) and those without (non-COVID cohort; n = 226), and evaluated their olfaction during the postpartum period by administering the University of Pennsylvania Smell Identification Test. Participants were queried about demographics, past SARS-CoV-2 infections, self-reported sense of smell (both in overall ability to smell and for the presence of qualitative smell issues such as parosmia and phantosmia), and perceived cause of smell loss, if any. We found significantly fewer postpartum women with normosmia capabilities in both COVID (27%) and non-COVID (46%) cohorts compared to normative data for aged-matched (30 to 39 years) women (83%). Women in the non-COVID cohort had significantly higher UPSIT scores and mean subjective olfaction ratings than those in the COVID cohort (95% CI [0.77,2.41] and 95% CI [−0.83,7.34], respectively). This study reflects the largest published cohort of postpartum women evaluated for olfactory function with standardized psychophysical testing. Our findings suggest both postpartum and SARS-CoV-2 infection are associated with diminished smell function.

The 2017 European Food Safety Authority (EFSA) recommendation of an acceptable daily intake (ADI) of 30 mg glutamic acid/kg bw/day did not take into consideration the primary energy sources during infancy, including infant formulas. In the present study, we determined total daily intakes of glutamic acid in a contemporary cohort of healthy infants who were fed either cow milk formula (CMF) or extensive protein hydrolysate formula (EHF); the formulas differed substantially in glutamic acid content. The infants (n = 141) were randomized to be fed either CMF or EHF. Dietary intakes were determined from weighed bottle methods and/or prospective diet records, and body weights were measured on 14 occasions from 0.5 to 12.5 months. Secondary data analysis determined the glutamic acid content of the diet over time. The trial was registered at http://www.clinicaltrials.gov/ as NCT01700205, 3 October 2012. Glutamic acid intake from formula and other foods was significantly higher in infants fed EHF when compared to CMF. As glutamic acid intake from formula decreased, intake from other nutritional sources steadily increased from 5.5 months. Regardless of formula type, every infant exceeded the ADI of 30 mg/kg bw/day from 0.5 to 12.5 months. Conclusion: Given that the ADI recommendation was not based on actual intake data of 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. What is Known:• The 2017 re-evaluation of the safety of glutamic acid-glutamates and the recommended acceptable daily intake (ADI) of 30 mg/kg bw/d by the European Food Safety Authority (EFSA) did not include actual intake data of the primary energy sources during infancy. What is New:• During the first year, glutamic acid intake from infant formula and other food sources exceeded the ADI of 30 mg/kg bw/day.

From an early age, humans can detect the umami taste sensation of the free amino acid glutamate, as evidenced by the facial expressions of pleasure displayed by newborns. This chapter briefly reviews the biology of umami flavor and summarizes the earliest routes of exposure to free amino acids in amniotic fluid, human milk, and infant formula, highlighting how exposure to free glutamate, and umami tastes, varies from gestation to postnatal feedings and from infant to infant. It then summarizes scientific evidence revealing that during infancy, the amount of free glutamate ingested impacts satiation and growth during milk feedings, as well as the development of preferences for similarly flavored foods. The study of umami as a basic taste during infancy and childhood has been neglected compared to other basic tastes, and gaps in knowledge are highlighted.

There is wide variation in how individuals perceive the chemosensory attributes of liquid formulations of ibuprofen, encompassing both adults and children. To understand personal variation in the taste and chemesthesis properties of this medicine, and how to measure it, our first scientific strategy centered on utilizing trained adult panelists, due to the complex and time-consuming psychophysical tasks needed at this initial stage. We conducted a double-blind cohort study in which panelists underwent whole-genome-wide genotyping and psychophysically evaluated an over-the-counter pediatric medicine containing ibuprofen. Associations between sensory phenotypes and genetic variation near/within irritant and taste receptor genes were determined. Panelists who experienced the urge to cough or throat sensations found the medicine less palatable and sweet, and more irritating. Perceptions varied with genetic ancestry; panelists of African genetic ancestry had fewer chemesthetic sensations, rating the medicine sweeter, less irritating, and more palatable than did those of European genetic ancestry. We discovered a novel association between TRPA1 rs11988795 and tingling sensations, independent of ancestry. We also determined for the first time that just tasting the medicine allowed predictions of perceptions after swallowing, simplifying future psychophysical studies on diverse populations of different age groups needed to understand genetic, cultural–dietary, and epigenetic factors that influence individual perceptions of palatability and, in turn, adherence and the risk of accidental ingestion.

Purpose. The 2017 European Food Safety Authority (EFSA) recommendation of an acceptable daily intake (ADI) of 30 mg glutamic acid/kg bw/d did not take into consideration the primary energy sources during infancy, including infant formulas. In the present study, we determined total daily intakes of glutamic acid in a contemporary cohort of healthy infants who were fed either cow milk formula (CMF) or extensive protein hydrolysate formulas (EHF); the formulas differed in glutamic acid content (262.4 mg/100ml, CMF; 436.2 mg/100ml, EHF). Methods. The infants (n = 141) were randomized to be fed either CMF or EHF. Daily intakes were determined from weighed bottle methods and/or prospective diet records, and body weights and lengths were measured on 15 occasions from 0.5 to 12.5 months. The trial was registered on http://www.clinicaltrials.gov/ as trial registration number NCT01700205 on 3 October 2012. Results. Glutamic acid intake from formula and other foods was significantly higher in infants fed EHF when compared to CMF. As glutamic acid intake from formula decreased, intake from other nutritional sources steadily increased from 5.5 months. Regardless of formula type, every infant exceeded the ADI of 30 mg/kg bw/d from 0.5 to 12.5 months. Conclusions. Faced with the knowledge that the EFSA health-based guidance value (ADI) was not based on actual intake data and did not account for the primary energy sources during infancy, EFSA may reconsider the scientific literature on growing children’s intakes from human milk, infant formula, and the complementary diet to provide parents and health care providers with revised guidelines.

We tested the hypotheses that mothers of infants who exclusively breastfed would differ in the trajectories of postpartum BMI changes than mothers of infants who exclusively formula fed, but such benefits would differ based on the maternal BMI status prepregnancy (primary hypothesis) and that psychological eating behavior traits would have independent effects on postpartum BMI changes (secondary hypothesis). To these aims, linear mixed-effects models analyzed measured anthropometric data collected monthly from 0.5 month (baseline) to 1 year postpartum from two groups of mothers distinct in infant feeding modality (Lactating vs. Non-lactating). While infant feeding modality group and prepregnancy BMI status had independent effects on postpartum BMI changes, the benefits of lactation on BMI changes differed based on prepregnancy BMI. When compared to lactating women, initial rates of BMI loss were significantly slower in the non-lactating women who were with Prepregnancy Healthy Weight (β = 0.63 percent BMI change, 95% CI: 0.19, 1.06) and with Prepregnancy Overweight (β = 2.10 percent BMI change, 95% CI: 1.16, 3.03); the difference was only a trend for those in the Prepregnancy Obesity group (β = 0.60 percent BMI change, 95% CI: −0.03, 1.23). For those with Prepregnancy Overweight, a greater percentage of non-lactating mothers (47%) gained ≥ 3 BMI units by 1 year postpartum than did lactating mothers (9%; p < 0.04). Psychological eating behavior traits of higher dietary restraint, higher disinhibition, and lower susceptibility to hunger were associated with greater BMI loss. In conclusion, while there are myriad advantages to lactation, including greater initial rates of postpartum weight loss regardless of prepregnancy BMI, mothers who were with overweight prior to the pregnancy experienced substantially greater loss if they breastfed their infants. Individual differences in psychological eating behavior traits hold promise as modifiable targets for postpartum weight management.