Effects of genetics on odor perception: Can a quick smell test effectively screen everyone?

SCENTinel®, a rapid smell test designed to screen for olfactory disorders, including anosmia (no ability to smell an odor) and parosmia (distorted sense of smell), measures four components of olfactory function: detection, intensity, identification, and pleasantness. Each test card contains one of nine odorant mixtures. Some people born with genetic insensitivities to specific odorants (i.e., specific anosmia) may fail the test if they cannot smell an odorant but otherwise have a normal sense of smell. However, using odorant mixtures has largely been found to prevent this from happening. To better understand whether genetic differences affect SCENTinel® test results, we asked genetically informative adult participants (twins or triplets, N=630; singletons, N=370) to complete the SCENTinel® test. A subset of twins (n=304) also provided a saliva sample for genotyping. We examined data for differences between the nine possible SCENTinel® odors; effects of age, sex, and race on SCENTinel® performance, test-retest variability; and heritability using both structured equation modeling and SNP-based statistical methods. None of these strategies provided evidence for specific anosmia for any of the odors, but ratings of pleasantness were, in part, genetically determined (h2=0.40) and were nominally associated with alleles of odorant receptors (e.g., OR2T33 and OR1G1; p<0.001). These results provide evidence that using odorant mixtures protected against effects of specific anosmia for ratings of intensity but that ratings of pleasantness showed effects of inheritance, possibly informed by olfactory receptor genotypes.

Using SCENTinel® to predict SARS-CoV-2 infection: insights from a community sample during dominance of Delta and Omicron variants.

Introduction: Based on a large body of previous research suggesting that smell loss was a predictor of COVID-19, we investigated the ability of SCENTinel®, a newly validated rapid olfactory test that assesses odor detection, intensity, and identification, to predict SARS-CoV-2 infection in a community sample. Methods: Between April 5, 2021, and July 5, 2022, 1,979 individuals took one SCENTinel® test, completed at least one physician-ordered SARS-CoV-2 PCR test, and endorsed a list of self-reported symptoms. Results: Among the of SCENTinel® subtests, the self-rated odor intensity score, especially when dichotomized using a previously established threshold, was the strongest predictor of SARS-CoV-2 infection. SCENTinel® had high specificity and negative predictive value, indicating that those who passed SCENTinel® likely did not have a SARS-CoV-2 infection. Predictability of the SCENTinel® performance was stronger when the SARS-CoV-2 Delta variant was dominant rather than when the SARS-CoV-2 Omicron variant was dominant. Additionally, SCENTinel® predicted SARS-CoV-2 positivity better than using a self-reported symptom checklist alone. Discussion: These results indicate that SCENTinel® is a rapid assessment tool that can be used for population-level screening to monitor abrupt changes in olfactory function, and to evaluate spread of viral infections like SARS-CoV-2 that often have smell loss as a symptom.

Stellate ganglion block for treating post-COVID-19 parosmia.

BACKGROUND: Post-COVID parosmia may be due to dysautonomia and sympathetic hyperresponsiveness, which can be attenuated by stellate ganglion block (SGB). This study evaluates SGB as a treatment for post-COVID olfactory dysfunction (OD). METHODS: Retrospective case series with prospective data of patients with post-COVID OD undergoing unilateral (UL) or bilateral (BL) SGB. Patients completed Brief Smell Identification Tests (BSIT) (12 points maximum) and post-procedure surveys including parosmia severity scores on a scale of 1 (absent) to 10 (severe). Scores were compared from before treatment (pre-SGB) to after first (SGB1) or second (SGB2) treatments in overall, UL, and BL cohorts. RESULTS: Forty-seven patients with post-COVID OD underwent SGB, including 23 UL and 24 BL. Twenty patients completed pre- and post-SGB BSITs (eight UL and 12 BL). Twenty-eight patients completed postprocedure surveys (11 UL and 17 BL). There were no differences in BSIT scores from pre-SGB to post-SGB1 or post-SGB2 for the overall (p = 0.098), UL (p = 0.168), or BL (p = 0.230) cohorts. Parosmia severity for the overall cohort improved from pre-SGB (8.82 ± 1.28) to post-SGB1 (6.79 ± 2.38) and post-SGB2 (5.41 ± 2.35), with significant differences from pre-SGB to post-SGB1 (p < 0.001) and pre-SGB to post-SGB2 (p < 0.001), but not post-SGB1 to post-SGB2 (p = 0.130). Number of parosmia triggers decreased for overall (p = 0.002), UL (p = 0.030) and BL (p = 0.024) cohorts. Quality of life (QOL) improved for all cohorts regarding food enjoyment, meal preparation, and socialization (p < 0.05). CONCLUSION: SGB may improve subjective parosmia and QOL for patients with post-COVID OD, however it may not affect odor identification. Further placebo-controlled studies are warranted.

Patient Insights into the Diagnosis of Smell and Taste Disorders in the United States.

OBJECTIVES: Diagnosis of smell/taste dysfunction is necessary for appropriate medical care. This study examines factors affecting testing and diagnosis of smell/taste disorders . METHODS: The online USA Smell and Taste Patient Survey was made available to US patients with smell/taste disorders between April 6-20, 2022. 4,728 respondents were included. RESULTS: 1,791 (38%) patients reported a documented diagnosis. Patients most often saw family practitioners (34%), otolaryngologists (20%), and Taste/Smell clinics (6%) for smell/taste dysfunction. 64% of patients who went to Taste/Smell clinics received smell testing, followed by 39% of patients who saw otolaryngologists, and 31% of patients who saw family practitioners. Factors associated with increased odds of diagnosis included age (25-39 years (OR 2.97, 95% CI [2.25, 3.95]), 40-60 (OR 3.3, 95% CI [2.56, 4.52]), and >60 (OR 4.25, 95% CI [3.21, 5.67]) vs. 18-24 years), male gender (OR 1.26, 95% CI [1.07, 1.48]), insurance status (private (OR 1.61, 95% CI [1.15, 2.30]) or public (OR 2.03, 95% CI [1.42, 2.95]) vs. uninsured), perception of their family practitioner to be knowledgeable (OR 2.12, 95% CI [1.16, 3.90]), otolaryngologic evaluation (OR 6.17, 95% CI [5.16, 7.38]), and psychophysical smell testing (OR 1.77, 95% CI [1.42, 2.22]). CONCLUSION: Psychophysical testing, otolaryngologic evaluation, patient assessment of family practitioner knowledge level, insurance, age, and gender are significant factors in obtaining smell/taste dysfunction diagnosis. This study identifies barriers to diagnosis including lack of insurance or access to specialist evaluation and highlights the importance of educating family practitioners in diagnosis and management of patients with smell/taste disorders.

More spice, less salt: How capsaicin affects liking for and perceived saltiness of foods in people with smell loss.

People who lose their sense of smell self-report consuming more salt to compensate for a lack of flavor and enhance eating enjoyment. However, this may contribute to excess sodium intake. Capsaicin may help increase salt taste intensity and eating enjoyment in people with smell loss, but this has not been studied in this population. The purpose of this study was to determine 1) whether salt intake in those with smell loss differs from population averages, 2) whether capsaicin increases flavor and salt taste intensity, and 3) if adding spice to foods increases liking in individuals with smell loss. Thirty-three participants 18-65 years old with confirmed smell loss for at least 12 weeks completed two sets of replicate test sessions (four total). In two sessions participants rated overall flavor intensity, taste qualities' intensities, spicy intensity, and liking for model tomato soups with low or regular sodium content and three levels of capsaicin (none, low, or moderate). In the other two sessions, participants rated the same sensory attributes for model food samples with three levels of added spice (none, low, or moderate). 24-hour urine samples were collected to determine sodium intake. Results indicate that although sodium intake is higher than recommended (<2300 mg/day) in those with smell loss (2893 ± 258 mg/day), they do not consume more sodium than population averages (3039 ± 100 mg/day; p = 0.3). Adding low and moderate amounts of capsaicin to a model tomato soup increased the intensity of overall flavor (p < 0.001) and saltiness (p = 0.004) compared to a model tomato soup without capsaicin. However, capsaicin's effect on liking differed by food type. Thus, capsaicin can improve flavor, salt taste intensity, and eating enjoyment in people with smell loss.

More spice, less salt: how capsaicin affects liking for and perceived saltiness of foods in people with smell loss.

People who lose their sense of smell self-report consuming more salt to compensate for a lack of flavor and enhance eating enjoyment. However, this can contribute to excess sodium intake and a poor diet. Capsaicin may help increase salt taste intensity and eating enjoyment in this population, but this has not been studied. The purpose of this study was to determine 1) whether salt intake in those with smell loss differs from population averages, 2) whether capsaicin increases flavor and salt taste intensity, and 3) if adding spice to foods increases food liking in individuals with smell loss. Participants 18-65 years old with confirmed partial or total smell loss for at least 12 weeks completed two sets of replicate test sessions (four total). In two sessions participants rated overall flavor intensity, taste qualities' intensities, spicy intensity, and liking for model tomato soups with low or regular sodium content and three levels of capsaicin (none, low, or moderate). In the other two sessions, participants rated the same sensory attributes for model food samples with three levels of added spice (none, low, or moderate). 24-hour urine samples were also collected to determine sodium intake. Results indicate that although sodium intake is higher than recommended in those with smell loss (2893 ± 258 mg/day), they do not consume more sodium than population averages. Adding low and moderate amounts of capsaicin to a model tomato soup increased the intensity of overall flavor and saltiness compared to a model tomato soup without capsaicin. However, the effect of capsaicin on liking differed by food type. In conclusion, the addition of capsaicin can improve flavor, salt taste intensity, and eating enjoyment in people with smell loss.

Low to moderate genetic influences on the rapid smell test SCENTinel™.

SCENTinel™ - a rapid, inexpensive smell test that measures odor detection, intensity, identification, and pleasantness - was developed for population-wide screening of smell function. SCENTinel™ was previously found to screen for multiple types of smell disorders. However, the effect of genetic variability on SCENTinel™ test performance is unknown, which could affect the test's validity. This study assessed performance of SCENTinel™ in a large group of individuals with a normal sense of smell to determine the test-retest reliability and the heritability of SCENTinel™ test performance. One thousand participants (36 [IQR 26-52] years old, 72% female, 80% white) completed a SCENTinel™ test at the 2021 and 2022 Twins Days Festivals in Twinsburg, OH, and 118 of those completed a SCENTinel™ test on each of the festival's two days. Participants comprised 55% percent monozygotic twins, 13% dizygotic twins, 0.4% triplets, and 36% singletons. We found that 97% of participants passed the SCENTinel™ test. Test-retest reliability ranged from 0.57 to 0.71 for SCENTinel™ subtests. Broad-sense heritability, based on 246 monozygotic and 62 dizygotic twin dyads, was low for odor intensity (r=0.03) and moderate for odor pleasantness (r=0.4). Together, this study suggests that SCENTinel™ is a reliable smell test with only moderate heritability effects, which further supports its utility for population-wide screening for smell function.

Proof-of-concept: SCENTinel 1.1 rapidly discriminates COVID-19-related olfactory disorders.

It is estimated that 20%-67% of those with COVID-19 develop olfactory disorders, depending on the SARS-CoV-2 variant. However, there is an absence of quick, population-wide olfactory tests to screen for olfactory disorders. The purpose of this study was to provide a proof-of-concept that SCENTinel 1.1, a rapid, inexpensive, population-wide olfactory test, can discriminate between anosmia (total smell loss), hyposmia (reduced sense of smell), parosmia (distorted odor perception), and phantosmia (odor sensation without a source). Participants were mailed a SCENTinel 1.1 test, which measures odor detection, intensity, identification, and pleasantness, using one of 4 possible odors. Those who completed the test (N = 287) were divided into groups based on their self-reported olfactory function: quantitative olfactory disorder only (anosmia or hyposmia, N = 135), qualitative olfactory disorder only (parosmia and/or phantosmia; N = 86), and normosmia (normal sense of smell; N = 66). SCENTinel 1.1 accurately discriminates quantitative olfactory disorders, qualitative olfactory disorders, and normosmia groups. When olfactory disorders were assessed individually, SCENTinel 1.1 discriminates between hyposmia, parosmia, and anosmia. Participants with parosmia rated common odors less pleasant than those without parosmia. We provide proof-of-concept that SCENTinel 1.1, a rapid smell test, can discriminate quantitative and qualitative olfactory disorders, and is the only direct test to rapidly discriminate parosmia.

Proof-of-concept: SCENTinel 1.1 rapidly discriminates COVID-19 related olfactory disorders.

It is estimated that 20-67% of those with COVID-19 develop olfactory disorders, depending on the SARS-CoV-2 variant. However, there is an absence of quick, population-wide olfactory tests to screen for olfactory disorders. The purpose of this study was to provide a proof-of-concept that SCENTinel 1.1, a rapid, inexpensive, population-wide olfactory test, can discriminate between anosmia (total smell loss), hyposmia (reduced sense of smell), parosmia (distorted odor perception), and phantosmia (odor sensation without a source). Participants were mailed a SCENTinel 1.1 test, which measures odor detection, intensity, identification, and pleasantness, using one of four possible odors. Those who completed the test (N = 381) were divided into groups based on their self-reported olfactory function: quantitative olfactory disorder (anosmia or hyposmia, N = 135), qualitative olfactory disorder (parosmia and/or phantosmia; N = 86), and normosmia (normal sense of smell; N = 66). SCENTinel 1.1 accurately discriminates quantitative olfactory disorders, qualitative olfactory disorders, and normosmia groups. When olfactory disorders were assessed individually, SCENTinel 1.1 discriminates between hyposmia, parosmia and anosmia. Participants with parosmia rated common odors less pleasant than those without parosmia. We provide proof-of-concept that SCENTinel 1.1, a rapid smell test, can discriminate quantitative and qualitative olfactory disorders, and is the only direct test to rapidly discriminate parosmia.

Almond consumption decreases android fat mass percentage in adults with high android subcutaneous adiposity but does not change HbA1c in a randomised controlled trial.

The purpose of this study was to determine if the mixed evidence of almond consumption on HbA1c stems from testing people with different body fat distributions (BFD) associated with different risks of glucose intolerance. A 6-month randomised controlled trial in 134 adults was conducted. Participants were randomly assigned to the almond (A) or control (C) group based on their BFD. Those in the almond group consumed 1·5 oz of almonds with their breakfast and as their afternoon snack daily. Those in the control group continued their habitual breakfast and afternoon snack routines. Body weight and composition were measured and blood samples were collected for determination of HbA1c, glycaemia and lipaemia at 0 and 6 months. Appetite ratings, energy intake and diet quality were collected at 0, 2, 4 and 6 months. Participants consuming almonds ingested 816 (sem 364) kJ/d more than participants in the control group (P = 0·03), but this did not result in any differences in body weight (A: -0·3 (sem 0·4), C: -0·4 (sem 0·4); P > 0·3). Participants in the almond, high android subcutaneous adipose tissue (SAT) group had a greater reduction in android fat mass percentage (A: -1·0 (sem 0·6), C: 1·1 (sem 0·6); P = 0·04), preserved android lean mass percentage (A: 0·9 (sem 0·6), C: -1 (sem 0·6); P = 0·04) and tended to decrease android visceral adipose tissue mass (A: -13 (sem 53) g, C: 127 (sem 53) g; P = 0·08) compared with those in the control, high SAT group. There were no differences in HbA1c between groups (A: 5·4 (sem 0·04), C: 5·5 (sem 0·04); P > 0·05). Thus, BFD may not explain the mixed evidence on almond consumption and HbA1c. Long-term almond consumption has limited ability to improve cardiometabolic health in those who are overweight and obese but otherwise healthy.

Systematic Review and Meta-Analysis on the Effect of Portion Size and Ingestive Frequency on Energy Intake and Body Weight among Adults in Randomized Controlled Feeding Trials.

Energy intake is the product of portion size (PS)-the energy content of an ingestive event-and ingestive frequency (IF)-the number of ingestive events per unit time. An uncompensated alteration in either PS or IF would result in a change in energy intake and body weight if maintained over time. The objective of this meta-analysis was to assess the independent effects of PS and IF on energy intake and body weight among healthy adults in randomized controlled trials (RCTs). A total of 9708 articles were identified in PubMed, Web of Science, Cochrane, and CINAHL databases. The articles were divided among 10 researchers; each article was screened for eligibility by 2-3 independent reviewers. Exclusion criteria included: populations <19 y and >65 y, unhealthy populations (i.e. participants with an acute or chronic disease), assessments <24 h and <4 wk in duration for trials investigating energy intake or body weight, respectively. Controlled feeding trials (i.e. fixed energy intake) that manipulated IF and PS in the same study intervention (IF/PS) were evaluated separately and for the body weight outcome only. Twenty-two studies (IF = 4, PS = 14, IF/PS = 4) met the inclusion criteria. There was an insufficient number of studies to assess the effect of IF, PS, or IF/PS on body weight. There was heterogeneity in the effect sizes among all comparisons (I2 ≥75%). Consuming larger portion sizes was associated with higher daily energy intake [295 kcal (202, 388), n = 24; weighted mean differences (WMD) (95% CI), n = comparisons], and increased frequency of ingestive events was associated with higher energy intake [203 kcal (76, 330), n = 10]. Results from RCTs support that larger PS and greater IF are both associated with higher energy consumption. However, there is insufficient information to determine chronic effects on body weight. This protocol was registered at the International Prospective Register of Systematic Reviews (PROSPERO) as CRD42018104757.

Finding the Sweet Spot: Measurement, Modification, and Application of Sweet Hedonics in Humans.

Sweetness is a sensation that contributes to the palatability of foods, which is the primary driver of food choice. Thus, understanding how to measure the appeal (hedonics) of sweetness and how to modify it are key to effecting dietary change for health. Sweet hedonics is multidimensional so can only be captured by multiple approaches including assessment of elements such as liking, preference, and consumption intent. There are both innate and learned components to the appeal of sweet foods and beverages. These are responsive to various behavioral and biological factors, suggesting the opportunity to modify intake. Given the high amount of added sugar intake in the United States and recommendations from many groups to reduce this, further exploration of current hypothesized approaches to moderate sugar intake (e.g., induced hedonic shift, use of low-calorie sweeteners) is warranted.

Low Calorie Sweeteners Differ in Their Physiological Effects in Humans.

Low calorie sweeteners (LCS) are prevalent in the food supply for their primary functional property of providing sweetness with little or no energy. Though tested for safety individually, there has been extremely limited work on the efficacy of each LCS. It is commonly assumed all LCS act similarly in their behavioral and physiological effects. However, each LCS has its own chemical structure that influences its metabolism, making each LCS unique in its potential effects on body weight, energy intake, and appetite. LCS may have different behavioral and physiological effects mediated at the sweet taste receptor, in brain activation, with gut hormones, at the microbiota and on appetitive responses. Further elucidation of the unique effects of the different commercially available LCS may hold important implications for recommendations about their use for different health outcomes.