Anxiety is a common mental illness, mental health in the patient’s quality of life and had a profound influence on overall health (1). Anxiety disorders are a devastating and very common clinical condition that is one of the major causes of global disability (2). These disorders are often accompanied by emotional instability, cognitive dysfunction, and social problems, placing a heavy burden on the patient and the family (3, 4). In order to better understand and treat these mental disorders, researchers have been searching for factors that may be related to the onset of mental impairment and the severity of symptoms.

Vitamin D is a fat-soluble vitamin that is critical not only for bone health, but also for immune system and nervous system function (5–7). In one study, 5.9% of Americans were considered to be vitamin D deficient (serum vitamin D concentration less than 30 mmol or 12 ng/mL), and 24% of Americans were considered to be vitamin D insufficient (serum vitamin D concentration less than 50 mmol or less than 20 ng/mL) (8). Recent studies have shown that vitamin D deficiency is associated with a variety of health problems, including cardiovascular disease, autoimmune disease, and neuropsychiatric disorders (9–11). Vitamin D is therefore not only an essential factor in the maintenance of physical health, but may also have a significant role to play in the onset and progression of mental health problems.

However, there is still some degree of uncertainty about the association of vitamin D with anxiety disorders. A cohort study from the National FondaMental Expertise Centre (FACE-SZ) found that vitamin D supplementation reduces symptoms of depression and anxiety, but treatment of patients with vitamin D deficiency remains inadequate (12), other studies did not find a significant association, for example, in a related study evaluating the relationship between serum vitamin D and anxiety in adult cancer patients before and after chemotherapy, no correlation was found between anxiety scores and serum vitamin D levels in either group (p > 0.05). In another study on vitamin D and mental health in pregnant adolescents in Iran, there was no statistically significant association between vitamin D and anxiety (p > 0.05) (13, 14).

Therefore, this study was to explore the relationship between serum vitamin D levels and anxiety and its internal mechanism. By gaining insight into these associations, we can better understand these common mental disorders and provide more information and possibilities for their prevention and treatment. These findings are expected to have a positive impact on clinical practice and public health policies in the field of mental health.

The object of study for a total of 12,232 people. Table 1 shows the characteristics of a stratified study population based on serum vitamin D quartiles from the National Health and Nutrition Examination Survey (NHANES) 2007–2012. The analyses revealed significant differences among serum vitamin D levels and various factors. In demographic characteristics, was significantly associated with age and serum vitamin D levels (p < 0.001). Significant differences (p < 0.001) were found between other variables such as gender, race, education, marital status, smoking status, drinking status, hypertension, body mass index, poverty income ratio, and serum vitamin D.

Table 2 shows the characteristics of the participants according to the number of days of anxiety. A total of 3,155 participants engaged in anxious behavior for 7 or more days in a 30-day period. The mean age of anxious subjects was 46.70 ± 16.22 years, which was significantly lower than the age of non-anxious subjects (50.25 ± 18.16 years, p < 0.001). It was also found that anxious subjects had higher body mass index levels than non-anxious subjects and lower serum vitamin D levels than non-anxious subjects (60.89 ± 24.14 nmol/L, p < 0.001). Females were more prone to anxiety (59.46%). Significant differences were found between the two groups in gender, age, body mass index, poverty income ratio, serum vitamin D, race, education, marital status, smoking status, drinking status, hypertension, and diabetes (p < 0.05).

In Table 3, logistic regression analyses were performed between each variable and anxiety. We found that females had a higher risk of anxiety compared to males (OR = 1.506, 95% CI: 1.349–1.681, p < 0.001), older people aged 60 years and above had a lower risk of anxiety compared to younger people aged 20–39 years, and those with high educational qualifications had a lower risk of anxiety compared to those with low educational qualifications. People who were living alone had a higher risk of developing an anxiety disorder, while non-smokers had a lower risk of developing an anxiety disorder.

Table 4 shows the relationship between serum vitamin D levels and anxiety. Participants were grouped according to the interquartile range (IQR) of serum vitamin D (Q 1: 0–25%; Q 2: >25–50%; Q 3: >50–75%; Q 4: >75%) and analyzed using Q 1 as the reference group. In Model 1, no adjustment was made for any of the variables. Serum vitamin D was significantly associated with anxiety in Q 4 compared to Q 1, with an OR and 95% CI of 0.774 (0.663, 0.903). The results of Model 2, adjusted for gender, age and race, showed that serum vitamin D levels were negatively associated with anxiety with an OR and 95% CI of 0.730 (0.621, 0.857). Model 3 was adjusted for all covariates. Serum vitamin D in Q4 was significantly associated with anxiety, with an OR and 95% CI of 0.781(0.669,0.912), respectively. In all three models, p for trend was less than 0.001.

We performed a smoothed curve fit as shown in Figure 2. Figure 2A is unadjusted for variables, showing that as serum vitamin D levels increase, anxiety risk decreases. In Figure 2B, when all variables were adjusted, anxiety risk decreased as vitamin D levels increased. In Figure 3, the results of the smoothed curve fit showed an overall decreasing trend in anxiety risk with increasing serum vitamin D levels after stratifying by gender, age, race, education, marital status, smoking status, drinking status, hypertension, and diabetes, respectively.

To our knowledge, this is the first article to use NHANES data to study the serum vitamin D-anxiety relationship. We use NHANES data of 2007–2012, and use weighted logistic regression and smoothing curve fitting analysis of serum vitamin D concentrations and the relationship between the risk of anxiety symptoms. The results showed that serum vitamin D was inversely associated with the risk of anxiety symptoms in adults.

Many studies have confirmed the beneficial effects of vitamin D on the development of anxiety disorders. A study has found that vitamin D supplements can effectively reduce the severity of generalized anxiety symptoms (18). Low vitamin D levels were linked to increased depression and anxiety symptoms in a study on the role of vitamin D in anxiety (19). In a about vitamin D supplement for older people with pre-diabetes the influence of anxiety and depression state of randomized controlled study, found that once a week for vitamin D supplement plan can effectively alleviate the high risk population of anxiety and depression symptoms (20). In addition, in a relatively young endurance athletes increase the intake of vitamin D may reduce mental anxiety (21). Finally, in a biological experiment, it was observed that mice exhibited increased anxiety-like behavior on behavioral tests after vitamin D deficiency (22).

Of course, some studies have reported results contrary to ours. There was no correlation found between depression and anxiety scores and serum vitamin D levels in a study assessing the relationship between serum vitamin D and B12 levels, nutritional levels, depression and anxiety in adult cancer patients before and after chemotherapy (13). In a study examining the relationship between vitamin D and anxiety and depression in pregnant adolescents, no relationship was found between serum vitamin D and anxiety or depression (14). In one of Australia’s young women 25—hydroxy serum vitamin D and the study of mental health, vitamin D status also proved to have nothing to do with depression or anxiety diagnosis report (23). Overall, there are inconsistent findings regarding the association between vitamin D and anxiety, which may be due to differences in demographic characteristics of the study samples, study design, environmental factors, seasonal variations, co-morbidities, and dietary habits.

The relationship between serum vitamin D and anxiety varies across demographic and lifestyle factors. Gender differences may be due to differential effects of sex hormones on vitamin D metabolism and the nervous system, whereas age differences may be related to age-related declines in the ability to synthesize vitamin D and more chronic health problems in older people. In terms of race differences, there may be genetic differences as well as social, cultural, and economic differences. Education level may reflect socioeconomic status and access to resources, while marital status may be associated with social support, family stress, and life stability. Smoking and drinking differences may relate to the effects of these habits on vitamin D metabolism and the immune system, as well as their relationship to ways of coping with stress and social activities. Finally, hypertension and diabetes differences may be due to the fact that chronic diseases indirectly affect anxiety levels by affecting the inflammatory responses (24, 25). Further research is needed in the future to confirm these findings and determine the reasons for this discrepancy.

A unique neurosteroid hormone, vitamin D’s receptors are found in neurons and glial cells in different parts of the brain, including the cingulate gyrus and hippocampus (26). Vitamin D with antioxidant and anti-inflammatory properties, promote neurogenesis and neural regulation, and adjust the gut microbiota (27). It in regulating neurotrophic factor, nerve protection, neural plasticity, brain development and neural immune adjustment plays an important role in the process of brain (28). Vitamin D deficiency may contribute to anxiety and depression (29).

Mechanisms of action between vitamin D and anxiety have been studied. Neurons and glial cells in different areas of the prefrontal cortex and hippocampus system expression of VDR and vitamin D metabolism enzymes, suggesting that vitamin D may play a role in anxiety (30). Positive regulation of antioxidant enzymes by osteotriol (a form of vitamin D) contributes to redox homeostasis and thus attenuates neuroinflammatory processes (31, 32). Vitamin D in the immune and nervous regulation part through its interaction with gut microbiota (33). Vitamin D deficiency, VDR, or CYP27B1 depletion has been shown to cause an increase in Mycobacterium anisopliae and Mycobacterium avium, triggering epithelial barrier dysfunction and intestinal inflammation. The positive regulation of antioxidant enzymes such as HO-1, CAT, and SOD by calcitriol contributes to the REDOX balance, thereby reducing the neuroinflammatory process (34, 35).

There are several benefits of our study as follows. To ensure the validity of our results, we used appropriate weighting and confounding adjustments in our analyses. Second, our sample size was large enough to effectively reveal the relationship between serum vitamin D and anxiety. Finally, we focused specifically on the relationship between serum vitamin D levels and anxiety. Compared to depression, relatively few studies have been conducted on the relationship between serum vitamin D and anxiety. There are also several flaws in our study. Firstly, because this was a cross-sectional study, it was not possible to determine a causal relationship between serum vitamin D and anxiety. Second, the measure of anxiety was a self-reported outcome by the subjects and may have been influenced by subjective factors. In addition, it was not possible to adjust for all covariates, and only those included were adjusted. Potential uncontrolled variables may still influence our conclusions. Finally, these data are from the American population and caution should be exercised when extrapolating to the population as a whole.

Serum vitamin D was inversely associated with anxiety. The future more prospective studies are needed to confirm this.

The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found at: https://www.cdc.gov/nchs/nhanes.

The studies involving humans were approved by National Center for Health Statistics Institutional Review Board. The studies were conducted in accordance with the local legislation and institutional requirements. Written informed consent for participation in this study was provided by the participants’ legal guardians/next of kin. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.

ZW: Conceptualization, Writing – original draft. LB: Conceptualization, Investigation, Software, Writing – original draft, Writing – review & editing. SW: Writing – review & editing. JC: Writing – review & editing. HJ: Writing – review & editing. JS: Writing – review & editing.