Summary of findings
In this study, which included a total of 8,427 participants, our study found that people who took nutrient supplements had a lower risk of depression, and that the greater the variety of nutrient supplements, the lower the risk of depression. Nutrient supplements involved in reducing the risk of depression mainly include calcium, vitamin A/D, and other nutrients. Further mediation analysis showed that physical activity played a mediating role in the association between nutrient supplements and depression. When we explored the mediating role of physical activity in the associations of different types of nutrients with depression, we found that physical activity played a mediating role in the associations of vitamin A/D supplements, calcium supplements, and other nutrient supplements.
Association between nutrient supplements and depression
Our study found that nutrient supplements use was inversely associated with the prevalence of depression. Moreover, this study also found that the prevalence of depression was also related to the number of nutrient supplements used, that is, the higher the number of nutrient supplements, the lower the risk of depression. Among the 8 nutrient supplements, the use of calcium, vitamin A/D, and other nutrients was most closely associated with depression. Currently, several studies have found that nutrient supplements reduce the risk of depression. One study found that micronutrient supplementation, especially zinc, was associated with a reduced risk of depression [34]. Another study also found that probiotic supplementation also alleviated depressive symptoms [35]. The current study found that nutrient supplementation can affect the occurrence of depression by affecting the function of the gut microbiota-brain axis [36]. In addition, studies have found the role of vitamin supplementation in alleviating depressive symptoms [13, 37]. Among many nutrient supplements, we found that calcium, vitamin A/D, and other nutrient supplements were closely associated with the prevalence of depression. Studies have found that calcium and vitamin D supplementation reduces the risk of depression [38]. Another study also found that vitamin D and calcium supplementation can affect depression scores by affecting inflammation and hormone levels [39]. Therefore, current acting evidence suggested that the use of nutrient supplements did help reduce depressive symptoms and reduce the risk of depression, and that a combination of supplements (such as calcium and vitamin D) may be even more effective.
Mediation of physical exercise
In this study, we also found that physical activity played a mediating role between the use of nutrient supplements and the prevalence of depression. In the sensitivity analysis, the mediating role of physical exercise remained robust. Current studies have found that physical activity itself can reduce the risk of depression or alleviate symptoms of depression [40, 41]. There were many possible mechanisms. For example, exercise could affect the levels of neurotrophic factors in brain cells, thereby promoting neuronal health and functional recovery in circuits and enhancing drug treatment response [42]. Second, exercise reduced the level of inflammation in the nervous system by reducing transcriptional co-activators of pro-inflammatory cytokine synthesis and release, as well as increased anti-inflammatory cytokines. However, in this study, we found a mediating effect of physical exercise, which may be because physical exercise could promote the absorption of nutrient supplements. In a systematic review, appropriate exercise was found to promote calcium absorption [20]. Another animal experiment found the same result [43]. Several current studies have found beneficial effects of physical activity and vitamin D supplementation on some negative outcomes, such as obesity [44], sarcopenia [45], and so on. In one study, exercise was found to promote an increase in vitamin metabolites after 8 days of fasting. The possible reason for this is that ingested vitamin D would be abundant in fat and skeletal muscle [46], and exercise could promote the decomposition of fat and thus promote the release of vitamin D [21–23]. Therefore, physical exercise could not only directly affect the occurrence of depression, but also played a mediating role by affecting the absorption and storage of nutrients.
Strengths and limitations
Data for this study were obtained from the CLHLS, a nationally representative survey study. Second, this study was one of the few cross-sectional studies based on a large sample to investigate the association between the use of nutrient supplements and the prevalence of depression in a Chinese population. Finally, this study explored the mediating role of exercise and provides a theoretical basis for the mechanism by which nutrient supplementation reduced the risk of depression. This study also has the following shortcomings. First, this study was a cross-sectional study, and the conclusions obtained need to be verified by a prospective cohort study. Besides, the use of self-reported measures of nutrient supplementation as exposure can be biased.