Age-related smell loss alone or in combination with loss of taste can have negative influences on an individual’s food preferences, diet, and nutritional status and may impact the overall health condition [1
]. Losses of smell and taste become a more common problem as people progress into adulthood and live longer and so pose a major risk to public health [2
]. In the US, people over the age of 40 years have a 13.5% probability of smell dysfunction and a 17.3% probability of taste dysfunction. Taste and smell decline markedly with age, can affect up to 60% of individuals aged over 65 years and 80% of individuals aged over 80 years and over, and is more common in men than women [2
Aging is one of the leading causes of smell loss due to cumulative damage to the olfactory receptor cells, ossification of the foramina of the cribriform plate, and changes in neural responsiveness [2
]. Other causes include head injuries, illnesses such as cancer and infectious disease, environmental hazards such as insecticides, and medications (i.e., some antibiotics and antihistamines) [5
]. Nutritional deficiencies also contribute to these deteriorations including trace metal deficiencies such as copper [6
], zinc [7
], and magnesium [8
] and some vitamin deficiencies including Vitamin A [9
], E [10
], and B12 [11
Vitamin D receptors are widely spread throughout the human brain and are involved in various brain neurotransmitters [12
]. Vitamin D can cross the blood–brain barrier and bind to those receptors [14
]. Mounting evidence has shown a relationship between Vitamin D deficiency and the nervous system, including impaired brain development and cognitive performance, as well as stroke, dementia, multiple sclerosis, Parkinson’s disease and epilepsy [15
Furthermore, the ubiquitous presence of Vitamin D receptors was detected in the olfactory system of the rat [17
], which has some striking similarities to the human olfactory system [18
]. Other animal studies showed that Vitamin D influences neural stem cells and progenitor cell proliferation [19
], creating various neuron types in the brain [20
] and olfactory system [21
]. Evidence on Vitamin D associated with the human olfactory system was recorded in one case report [22
However, the role of Vitamin D on age-related smell and taste impairments among adults has never been examined in a large population-based study. Given this background, and to fill the void in knowledge, this study aims to examine the association between Vitamin D deficiency and smell and taste impairments and effect modification of age in the population of the US. This study hypothesizes that there are significant associations between Vitamin D deficiency and smell and taste impairments, being higher among older people.
To the best of the author’s knowledge, this is the first epidemiological study that examined the relationships between Vitamin D and smell and taste impairments among national representative adult samples from the US. This study sheds light on the potential mechanism that may link Vitamin D deficiency and age-adjusted smell impairment. Specifically, this study showed that participants with Vitamin D deficiency, serum 25(OH)D concentrations below 20 ng/mL, were more likely by 39% to report smell impairment compared to those with sufficient Vitamin D, serum 25(OH)D concentrations above 30 ng/mL, after adjusting for significant confounders such as age, gender, race/ethnicity, and history of cancer.
This study also showed that only participants aged 70–80 years with Vitamin D adequacy, serum 25(OH)D concentrations of 20–30 ng/mL, were more likely by 96% to report taste impairment compared to participants with sufficient Vitamin D after adjusting for significant confounders such as age, gender, race/ethnicity, CVD and BMI. However, such a significant relationship between Vitamin D and taste impairment was not observed among participants younger than 70 years of age. More studies with improved methods are needed to explore such a potential association.
In the literature, limited studies have investigated Vitamin D deficiency and its relationships with smell and showed similar findings. For example, a study of a few reported cases showed that olfactory dysfunction has subjectively been detected in adult patients with Vitamin D deficiency and it was improved with increasing serum Vitamin D [22
]. Another study found that low serum (25(OH)D) concentrations were independently associated with olfactory dysfunction among Parkinson’s disease patients [33
]. However, similar studies regarding Vitamin D and taste dysfunction were not found in the literature.
Ample epidemiological studies showed that Vitamin D deficiency is associated with brain health including cognitive function, neuropsychiatric disorders [34
] and mood regulation [7
]. This stems from the fact that Vitamin D receptors are widely spread throughout the central and peripheral nervous systems and have an impact on various neurotransmitters [12
]. Some animal studies have shown that the rat olfactory system contains numerous target sites of Vitamin D receptor [17
], which emphasizes the unique functional importance of 1,25-dihydroxy Vitamin D3 in olfactory function [33
]. Since Vitamin D functions as a neurosteroid hormone in the brain, spinal cord, and olfactory system [36
], a lack of Vitamin D may lead not only to the neurological decline of the central and peripheral nervous system but also of the cranial nerves, causing a reduction in olfactory perception [22
], which may explain the significant finding observed in the current study.
However, this study did not find a significant relationship between Vitamin D deficiency and taste impairment. It seems that although smell and taste are often grouped, the brain processes them differently, and so each possesses unique mechanisms and associated causes [2
]. This was also confirmed in this study, as no significant relationship between smell and taste impairments was observed, and therefore, participants in this sample with smell impairment did not necessarily have taste impairment. Taste receptors are associated with cranial nerves VII, IX, and X, which are linked to the gustatory cortex of the brain [38
], while smell receptors are associated with cranial nerve I, which is linked to the olfactory cortex [39
]. Since only two tastes were examined in this study, as opposed to eight odorants in the smell examination, subsequent studies might need to add more tasting such as sweet, sour, and umami when examining the association with Vitamin D deficiency among adults.
People with smell or taste dysfunction tend to report common symptoms such as a loss of appetite, or changes in food intake including meats, fresh fruits, coffee, eggs, and carbonated beverages [40
]. In the current sample, however, participants with smell or taste impairment did not report differences in their calorie intakes, in their dietary intake of Vitamin D or in their BMI compared to those with normal assessments of smell and taste. This might be due to compensating with other food intakes, thus maintaining the total energy intake. Other changes related to culinary habits are also common when a decrease in smell and taste occurs, such as increased salt, sugar, and fat use, which could also cause other health issues such as hypertension, diabetes, and CVD, but were not assessed in this study [40
The present study had several strengths. This study utilized data from the NHANES, which employed standardized protocols and rigorous quality control in data collection and reporting. The large sample of individuals is representative of the US population; therefore, these results can be applied to the US population, but they may not be applied to other populations who may have different predispositions for smell and taste impairments and Vitamin D metabolism. In addition, Vitamin D was measured via serum 25(OH)D concentrations using tandem LC–MS/MS, which is considered a standard methodology that allows comparison to other national surveys. Smell assessments employed a relatively valid number of odorants and impairment corresponds to the UPSIT [29
The NHANES has a large, rich and unique database that was used to examine the target hypotheses while controlling for well-established confounders associated with smell and taste impairments such as age, gender, race/ethnicity [4
], and associated chronic diseases including cancer, diabetes [42
], CVD and asthma to ensure an accurate and valid estimation of the findings. Individuals who had reported problems with their nose, such as nasal/sinus congestion were excluded to properly assess primary exposure with age-related smell loss.
To the author’s knowledge, this is the first large-scale well-designed epidemiological study to explore the association between Vitamin D and smell and taste impairments using population-based adult samples. The significant findings indicate a possible mechanism between Vitamin D and the olfactory system across age groups, which bridges a gap in knowledge in this field.
The present study also had several limitations. A cross-sectional design was used to evaluate the relationship between serum 25(OH)D concentrations and current smell and taste status. However, in conclusion, temporality and causality relationships are impossible. Although a representative sample of adults aged 40 and over living in the US was used, the findings should be extrapolated with caution outside these limits.
The assessment of smell and taste impairments was measured only one time, and may not be reproducible over longer period. In the taste assessment, the NHANES only utilized two tastings, bitter and salt, which might not be sensitive enough to capture age-related taste loss. Further, the type of smell test used by the NHANES only measures the ability to identify a particular odor but does not measure sensitivity or the threshold to certain smells. Therefore, this study did not differentiate between smell disorders caused by a decrease in the ability to smell or changes in the way a person perceives odors.
There are additional age-related health conditions that may directly cause smell and taste impairments such as Parkinson’s disease, Alzheimer’s disease, and hypothyroidism [33
]. Furthermore, data on medications (i.e., some antibiotics and antihistamines) that can potentially influence taste impairment were not included, which might also affect serum Vitamin D [5