Olfaction and gustation are essential senses that significantly contribute to the perception and experience of daily life for human beings (1). Olfactory dysfunction (OD) and gustatory dysfunction (GD) have negative effects on various aspects of an affected population, such as appetite, nutrition, social functioning, and even environmental safety (2). Recent epidemiological studies have indicated a high prevalence of OD and GD, particularly among older adults, underscoring their importance as public health concerns within gerontology. In a nationwide household health survey involving 142.5 million adult Americans, approximately 10.6% of respondents self-reported OD, while 5.3% self-reported GD (3). The prevalence of dysfunction increased with age: OD affected 24.5% of adults aged 53–97, reaching 62.5% in those aged 80–97 (4), while severe GD was reported in 14.8% of adults aged 57–85 (5). With aging, taste and smell decline significantly due to cumulative damage and a reduction in the number of olfactory and gustatory receptor cells, as well as changes in neural responsiveness (6–8). Consequently, research on OD and GD is of great significance and has recently become a hot topic.

The etiology of OD and GD is not fully understood, and multiple risk factors contribute to their development (9). These factors include systemic diseases [such as metabolic and endocrine disorders (10) and neurological disorders (11)], diseases of the nose and pharynx [including inflammation of the nasal meatus and sinuses (12), head trauma and surgery (13)], environmental factors [such as chemical exposures (14)], and even normal aging (15). These factors interact and play important roles in the development of both dysfunctions. With an aging global population and increasing environmental pollution, the incidence of OD and GD is expected to continue to rise (8). Therefore, gaining deeper insights into the relationship between OD and GD will shed new light on our understanding of the human olfactory and gustatory systems.

Preliminary studies supported that there may be a relationship between OD and GD. It has been demonstrated that OD and GD often coexist within one patient (16). Importantly, olfaction and gustation both rely on the same central nervous site, located at the orbitofrontal cortex (17). This commonality of neuroanatomical structures of olfaction and gustation could support the association of OD and GD. Moreover, olfactory information can transmit through two pathways: the nose through the anterior nares (orthonasal olfaction) and the mouth through the oropharynx (retronasal olfaction). The latter pathway may be associated with gustation formation, which is currently a popular research topic (18–23).

At present, there is a lack of population-based epidemiological studies examining the correlation between OD and GD. The National Health and Nutrition Examination Survey (NHANES), conducted by the National Center for Health Statistics (NCHS) and Centers for Disease Control and Prevention (CDC), systematically and continuously collects and analyzes health-related data, including the prevalence of OD and GD (24). Therefore, to provide comprehensive epidemiological evidence, this study aimed to investigate the relationship between OD and GD using both measurement and questionnaire data from the 2013–2014 NHANES for US adults aged 40 years and older.

In 2013–2014, a total of 2,582 adult NHANES participants completed olfactory and gustatory testing (both measurements and questionnaire). In the mOD group, 2.9% of the participants suffered from anosmia, and 12.0% suffered from hyposmia (Supplementary Table S2). In mGD-t group, 12.4% had ageusia, while 53.0% had hypogeusia (36). In mGD-w group, 0.7% had ageusia, while 18.3% had hypogeusia (Supplementary Table S3). The overall estimated prevalence of qOD was 20.7%, whereas it was 13.4% for qGD (Supplementary Table S4).

The baseline population characteristics of individuals with mGD-w are presented in Table 1. A total of 2,582 participants were included, of whom 473 (18.3%) had hypogeusia of mGD-w and 19 (0.7%) had ageusia of mGD-w (Supplementary Table S3). Among the total population, 48.8% were male, and 47.7% were aged over 60 years. The major ethnicities were non-Hispanic White (48.5%) and non-Hispanic Black (20.4%). 58.5% had some college/equivalent and College graduate or above, and 36.6% had a household income with a PIR > 3.5. Additionally, 61.2% had a BMI less than 30. Current smokers accounted for 17.8%, while 72.9% were drinkers. Hyposmia was present in 12% of the population, and anosmia in 2.9% (Supplementary Table S2). Univariate comparisons show difference in race, education level, BMI, and mOD incidence. The baseline population characteristics of participants with qGD and mGD-t are presented in Supplementary Tables S7, S8, respectively.

In Table 2, for the unadjusted model, anosmia of mOD strongly increased the odds of hypogeusia of mGD-w (OR: 11.29, 95% CI: 4.55–28.01) or ageusia of mGD-w (OR: 10.78, 95% CI: 3.86–30.08). After adjusting for confounding factors in Model 1 (demographic characters), Model 2 (Model 1 + systemic diseases), and Model 3 (Model 2 + diseases of the nose and pharynx), anosmia of mOD significantly increased the odds of hypogeusia of mGD-w (aOR:16.16, 95% CI:4.18–42.29; aOR: 18.18, 95% CI: 5.95–55.53; aOR:17.65, 95% CI:5.49–56.74) or ageusia of mGD-w (aOR:14.09, 95% CI:4.66–42.60; aOR: 15.64, 95% CI: 5.04–48.55; aOR:15.83, 95% CI:5.03–49.89), respectively. There is no association between hyposmia of mOD and mGD-t (Table 3) or between anosmia of mOD and mGD-w (Table 4). Interestingly, for the unadjusted model, we found that hyposmia of mOD decreased the odds of hypogeusia of mGD-t (OR: 0.63, 95% CI: 0.46–0.86), which persisted after model adjustment (aOR: 0.69, 95% CI: 0.50–0.95; aOR: 0.68, 95% CI: 0.50–0.94; aOR: 0.68, 95% CI: 0.49–0.94), as shown in Table 5.

Regarding the association between qOD and qGD (Table 6), qOD significantly increased the odds of qGD, both for the unadjusted model (aOR: 5.90, 95% CI: 4.17–8.35) and for the adjusted model. After adjusting for confounding factors in Model 1, Model 2, and Model 3, qOD significantly increased the odds of qGD (aOR: 5.68, 95% CI: 4.06–7.94; aOR: 5.43, 95% CI: 3.81–7.75; aOR: 5.10, 95% CI: 3.52–7.38, respectively).

Although several epidemiological studies have reported the prevalence of OD and GD, there is a dearth of research exploring the correlation between these two dysfunctions in a large sample. In this study, we utilized a nationally representative sample of participants from the United States as our target population. For the first time, we provide robust evidence to establish a strong association between OD and GD, which was supported by both objective measurements and questionnaire responses after adjusting for confounding factors. Our measurements revealed a significant association between anosmia of mOD and two mGD-w groups including hypogeusia (aOR: 17.65, 95% CI: 5.49–56.74) and ageusia (aOR: 15.83, 95% CI: 5.03–49.89). Interestingly, hyposmia of mOD decreased the odds of hypogeusia of mGD-t (aOR: 0.68, 95% CI: 0.49–0.94). Additionally, our questionnaire-based analysis demonstrated a significant increase in the odds of experiencing qGD among individuals with qOD (aOR: 5.10, 95% CI: 3.52–7.38).

Due to declining fertility rates and increasing life expectancy (37), the global population is undergoing unprecedented aging. This demographic shift is expected to have profound impacts on various societal aspects, particularly public health (38). Recent data indicate that the proportion of individuals aged 65 years and older accounted for 9.3% of the global population in 2020, and this proportion is projected to rise to 20% by 2050 (39). A hallmark of the aging process is the gradual decline in sensory functions (40). These declines may be interrelated, and investigating their underlying connections to interrupt the “cascade effect” of aging holds significant public health implications. Olfactory and gustatory dysfunctions are prominent issues in the aging population, leading to a substantial decline in quality of life and imposing a considerable burden on public health systems (41). Furthermore, these sensory impairments are closely associated with cognitive decline in older adults (27, 42, 43). From an epidemiological perspective, our study confirms the close association between olfactory and gustatory dysfunctions, providing valuable insights into the mechanisms of aging and potential strategies to delay its progression.

Regarding the diagnosis of OD and GD in this study, we used previously adopted measurements and questionnaires (9, 12, 35). Diagnosis by measurements and questionnaires has the advantage of being reproducible over a 6-month period (44). The measurements for OD and GD diagnosis were reported to be reliable and objective (9, 22, 27, 33, 35), although there is a lack of unified international measurement standards. Questionnaires are easily available, accessible and internationally unified (3, 20).

The close association of OD and GD could be explained by a common integrated central cortex (23). Some studies suggest that gustatory and olfactory information converges at the orbitofrontal cortex on the central nervous system (17). Moreover, some studies have indicated that the processing of retronasal olfactory input occurs in brain regions responsible for taste perception (45).

Previous studies on OD and GD have shown that functional MRI (fMRI) is meaningful in exploring taste and smell phantoms (46), post-traumatic olfactory loss (47), and congenital hyposmia (48). However, its application in the clinical assessment of OD and GD remains limited (49). The primary reason is the significant inter-individual variability in olfactory and gustatory fMRI imaging data, making it unrealistic to consider fMRI as a clinical diagnostic tool for OD and GD (50). Furthermore, studies on the impact of COVID-19 on olfactory and gustatory dysfunctions found that fMRI failed to detect evidence of neuroinvasion (51). Therefore, fMRI for clinical evaluation of OD and GD still needs to overcome these limitations.

Furthermore, the association of OD and GD is also established by the common constitution of olfaction and gustation. Olfactory information is transmitted through two pathways: orthonasal olfaction via the nose (anterior nares) and retronasal olfaction via the mouth (oropharynx) (52). Both pathways convey odors to the olfactory cleft, generating gustatory information. Therefore, when olfaction is impaired, both orthonasal and retronasal olfaction may exhibit similar degrees of impact (53). Previous research has demonstrated that whole mouth gustation is influenced not only by the function of the taste buds, including those on the tip of the tongue (54) and other regions (55), but also by retronasal olfaction (56). Thus, retronasal olfaction plays an important role in whole-mouth gustation.

In this study, we found that anosmia of mODs increased the odds of mGD-w. When anosmia of mODs occurs, the complete loss of retronasal olfaction disrupts the normal generation of gustation, inducing mGD-w (Figure 2A). In our study, after adjusting for confounding factors in Models 1, 2, and 3, anosmia of mOD significantly increased the odds of hypogeusia of mGD-w (aOR: 17.65, 95% CI: 5.49–56.74) and ageusia of mGD-w (aOR: 15.83, 95% CI: 5.03–49.89).

In addition to measurements, the association between OD and GD was supported by questionnaire data. This study also found a strong correlation between self-reported qOD and qGD (aOR: 5.10, 95% CI: 3.52–7.38). This can be explained by the fact that when the OD is severe to the extent of self-perception, it would cause a self-perception of GD to a certain extent.

When hyposmia of mOD occurs, the function of taste buds on the tongue tip increases, which represents the decreased odds of mGD-t (Figure 2B). In our study, we interestingly found that hyposmia of mOD decreased the odds of hypogeusia of mGD-t (aOR: 0.68, 95% CI: 0.49–0.94). The association may be attributed to compensatory mechanisms in sensory systems (57, 58). Some literature suggests that a reduction in olfaction may trigger enhanced responses in the taste buds on the tongue tip (59–61). Therefore, when hyposmia of mOD occurs, the function of taste buds on the tongue tip may increase, which means decreased odds of mGD-t.

Reported OD and GD prevalence are varied. A study of 742 individuals due to preoperative evaluation or subjective OD and/or GD (median age was 55 years) revealed that 65.8% had mOD, 15.9% had mGD, 45.4% had qOD and 6.5% had qGD (22). In a review including a non-clinical population, qOD prevalence estimates ranged from 2.7 to 7.8%, while qGD ranged from 5 to 20% (62). A study including 3,005 adults (older than 55 years) in the US revealed that severe qOD was 2.7% and severe qGD was 14.8% (5). In our study including US adults older than 40 years of age, 7.0% of the population suffered from mOD, 35.0% had mGD-t, 26.7% had mGD-w, 20.1% had qOD, and 13.4% had qGD. The different prevalences may be due to the non-uniform diagnostic criteria for OD and GD (measurements or questionnaires) or the diverse characteristics of the population.

Multiple studies have reported a high comorbidity rate between OD and GD (63). For instance, in a study with a median age of 55 years, among 488 patients with mOD, 93 individuals (19.1%) also exhibited mGD (20). Similarly, in patients attending a specialized smell and taste clinic, 67.8% of the individuals in the qGD population were comorbid with qOD (16). In our study including 385 participants suffering from mOD, the comorbidity rates were 21.8% (84 individuals) for mGD-w and 71.6% (276 individuals) for mGD-t. Additionally, among 535 participants with qOD, 33.5% (179 individuals) had qGD. The consistency of these high comorbidity rates across various studies further supports the close relationship between OD and GD.

This study has several notable strengths. First, it offers a nationally representative estimate of the association between OD and GD based on a substantial sample from the US population. Second, to evaluate that relationship, this study employed both objective measurements and comprehensive questionnaires while carefully controlling for various demographic and disease-related factors. The integration of these two approaches substantially enhances the overall credibility of the research findings. However, certain limitations of this study should be acknowledged. First, due to its cross-sectional nature, the investigation was unable to establish causal relationships between OD and GD. Further longitudinal studies are necessary to explore potential cause-and-effect associations. Second, the gustation assessment in the NHANES only covered bitter and salt stimuli, thereby excluding the evaluation of responses to sweet and sour tastes. In the future, a more comprehensive taste assessment, including salt, bitterness, sweetness, and sourness, is needed to objectively detect GD and measure its degree. On this basis, we explore the relationship between OD and GD.

The influences of OD and GD on disease and health have not been fully elucidated. For future olfactory and gustatory studies, it is imperative to establish internationally uniform diagnostic criteria, incorporating both objective measurements and standardized questionnaires. These studies should encompass diverse populations, including individuals from various age groups and ethnic backgrounds. To establish a causal relationship between OD and GD, long-term follow-up investigations are essential. Such comprehensive research will contribute significantly to our understanding of the impact of both sensory dysfunctions on overall health and disease outcomes.