Our results showed that, among participants from 9 states and 1 territory of the United States, use of folic acid supplements 1-4 times/day (50.2% versus 38.7%) and use of vitamin supplements (62.5% versus 49.8%) were significantly higher among women than among men. Men with ever diagnosed depression were more likely to report taking folic acid and vitamin supplements than men with no history of diagnosed depression regardless whether they had elevated depressive symptoms. In contrast, although women with ever diagnosed depression were significantly more likely to report taking folic acid 1-4 times/day and vitamin supplements than were women with no history of diagnosed depression, these differences were no longer statistically significant when the status on elevated depressive symptoms was taken into consideration.
To date, most previous studies have mainly focused on the causal relationship between folate and mental disorders. The results of these studies suggest that folate or folinic acid (5-methyltetrahydrofolate) may serve as a stand-alone treatment of depression [50, 51] or an augmentation of antidepressant treatment showing a significant beneficial effect in reducing Hamilton Depression Rating Scale Score when used with other psychotropic medication [52–57]. Limited evidence from the Vitamins and Lifestyle (VITAL) study showed that 10.4% of participants with depression who were taking medications for depression reported taking dietary supplements and that 6.7% of those who felt depressed or anxious but did not take medication for depression reported doing so . In that study, participants were limited to the 50 to 75 years of age, and dietary supplements were a combination of 17 supplements including folic acid and various other vitamins. To our knowledge, our study is the first population-based study to focus on the behaviors of use of folic acid and vitamin supplements among adults with depression or anxiety. Although our results showed that men with ever diagnosed depression or anxiety and women with ever diagnosed depression were more likely than those without a history of these conditions to report taking folic acid supplements (1-4 times/day), only about 50% of them were doing so. Most importantly, we found that adults with elevated depressive symptoms were only as likely as those without these symptoms to report taking folic acid supplements. At present, studies have consistently reported a high prevalence of depressive symptoms in populations [3, 45, 59], and these symptoms are strongly associated with first-onset major depression . In addition, most depressive symptoms are often unrecognized and untreated in clinical practice. Given the links between folate deficiency and depressive symptoms [9–28], the use of folic acid supplements may possibly prevent or delay the onset of major depression among people with elevated depressive symptoms, although randomized trials are needed to confirm it.
Other than folate, studies have shown that low levels of vitamin B6 and B12 were also related to depressive disorders [16, 19, 23, 26, 27, 60–62], however, other studies failed to show any relationship between vitamin B12 and depressive symptoms [12, 20, 25, 30]. Similarly, high intakes of vitamins B6 and B12 have shown to be protective of depressive symptoms in a prospective study , but not in others [34, 37]. Thus, the controversial results remained to be elucidated in the future. Nonetheless, B-vitamins including B6 and B12 have known to be important for essential functioning of the one-carbon metabolism in the biosynthesis of monoamine neurotransmitters including serotonin, dopamine, norepinephrine, and epinephrine [60–62], all of which are known to affect mood and cognition. Our results showed that, although adults with ever diagnosed depression were significantly more likely to report taking vitamin supplements than those with no history of diagnosed depression, only less than two-thirds of them reported taking vitamin supplements. Taken together, our results call for further research or clinical trials that may help to establish whether the use of folic acid and vitamin supplements should be improved among people with mental disorders.
Our results further demonstrated that men with ever diagnosed anxiety were significantly more likely to report taking folic acid and vitamin supplements, although these relationships were not observed among women with anxiety. At present, the relationship between anxiety and use of folic acid and vitamin supplementats is unknown. However, given the high prevalence of anxiety in the U.S. population [3, 45] and its coexistence with depression , further investigation of the role of folic acid and vitamin supplementation in the prevention and treatment of anxiety is needed.
There are several limitations in the present study. First, all data were based on the self-reports by survey participants and thus subject to recall bias. Second, the information on the severity and diagnosis date of mental disorders was not available in the BRFSS. Third, given the cross-sectional nature of the survey, the temporal relationship between the use of folic acid and vitamin supplements and the presence of depression, anxiety, or elevated depressive symptoms cannot be established in the present study. Evidence suggests that folate/vitamin deficiency may affect one-carbon metabolic pathway and neurotransmitter synthesis in the central nervous system, thereby linking to depressive disorders. On the other hand, people who are diagnosed with mental disorders may be more likely to take dietary supplements. Thus, bidirectional associations may exist. Fourth, although we have assessed the frequency of folic acid supplementation, the amount of daily folic acid and vitamin intake as well as the biomarkers of folic acid and vitamin supplementation (i.e., serum or red blood cell folate levels, serum homocysteine levels, or serum vitamin levels) was unknown in the present study. Also, data on dietary intake of folate and vitamins as well as dietary energy intake were not available in the BRFSS so we were unable to assess whether these variables may have confounding effects. Fifth, women of reproductive age may be more likely to take folic acid and vitamin supplements. In addition, people with chronic conditions such as cardiovascular disease and diabetes may confer higher risks for depression. Thus, further stratified analysis in women of childbearing age or in people with chronic conditions are warranted in future studies. Finally, use of prescribed medications (including prescribed folate or other supplements that contain folate) for depression, anxiety, or other mental disorders was not ascertained, thus, we were unable to conduct stratified analyses by medication use.