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Depression with low vitamin D increased risk of CVD and Cancer deaths – Jan 2024

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Association of serum 25-hydroxyvitamin d concentrations with all-cause and cause-specific mortality among individuals with depression: A cohort study

Journal of Affective Disorders https://doi.org/10.1016/j.jad.2024.02.018
Yafei Mao a b, Xinyuan Li a, Yanming Li a, Shumin Zhu a, Xu Han b, Rui Zhao b, Yulan Geng a

Background
Limited evidence exists on the relationship between vitamin D status and mortality in depressed patients.

Methods
This study investigates serum 25-hydroxyvitamin D [25(OH)D] concentrations in 8417 adults with depression among the National Health and Nutrition Examination Survey (NHANES, 2005–2018). Mortality outcomes were assessed through National Death Index records up to December 31, 2019. Cox proportional risk models estimated risk ratios (HR) and 95 % confidence intervals (CI) for all-cause, cardiovascular disease (CVD), and cancer mortality. Restricted cubic spline analyses explored the nonlinear association of serum 25(OH)D levels with mortality, using the likelihood ratio test for nonlinearity.

Results
The weighted mean serum 25(OH)D level was 66.40 nmol/L (95 % CI: 65.8, 67.0), with 36.3 % having deficient vitamin D (<50 nmol/L [20 ng/mL]). Over an average 7.16-year follow-up, 935 deaths were documented, including 296 CVD deaths and 191 cancer deaths. Higher serum 25(OH)D levels were associated with reduced all-cause mortality (HRs 0.55–1.00, p trend = 0.006) and cancer-specific mortality (HRs 0.36–1.00, p trend = 0.015) after multivariate adjustment. The relationship between serum 25(OH)D and all-cause mortality exhibited a nonlinear pattern (P for nonlinearity <0.001), with a 34 % lower risk for each unit increase in natural log-transformed 25(OH)D levels. Significant interactions were observed with age, antidepressant use, and diabetes status.

Conclusions
Higher serum 25(OH)D levels were associated with decreased all-cause and cancer-specific mortality in depressed adults, particularly among younger individuals and those using antidepressants or without diabetes. Further research is essential to understand mechanisms and interventions related to vitamin D in depression.

Introduction
Depression is a global public health concern (Marwaha et al., 2023), affecting about 4.4 % to 5.0 % of the population, and is associated with diminished quality of life and increased mortality risk (Ferrari et al., 2013). It is linked to several severe illnesses, including cardiovascular disease, stroke, Alzheimer's disease, cancer, and diabetes, all of which contribute to heightened mortality rates (Van der Kooy et al., 2007; Pan et al., 2011; Saiz-Vazquez et al., 2021; Chen and Lin, 2011; Yu et al., 2015; van den Berg et al., 2016). Cohort studies consistently report a positive association between depression and mortality (van den Berg et al., 2016; Meng et al., 2020; Rajan et al., 2020; Wei et al., 2022; Wicke et al., 2022). Identifying modifiable factors is essential to prevent premature mortality in individuals with depression.

Vitamin D, a crucial hormone, plays a central role in calcium and phosphate metabolism (Holick, 2007), and is associated with various diseases beyond skeletal health (Eyles et al., 2013; Grober et al., 2013). It directly influences gene regulation, impacting processes like cellular proliferation, vascular calcification, and inflammatory responses. Additionally, it indirectly affects the renin-angiotensin-aldosterone system (de Borst et al., 2011). Moreover, vitamin D has the capacity to modulate neurotransmitter systems, including cholinergic, dopaminergic, and noradrenergic systems, which are linked to neuropsychiatric disorders, including depression (Eyles et al., 2013).

The potential role of vitamin D in depression has garnered significant attention, with epidemiological evidence suggesting an association between vitamin D deficiency and an elevated risk of depression (de Oliveira et al., 2018; Wong et al., 2018), and some indications that vitamin D supplementation may have certain benefits (Spedding et al., 2013; Thacher and Clarke, 2011). However, some studies have not found a link between vitamin D levels and depression (Cartier et al., 2017). Yet, research on the correlation between vitamin D deficiency and all-cause mortality in individuals with depression remains limited. As an illustration, within the elderly demographic, vitamin D deficiency has also been correlated with frailty and heightened mortality rates (Hirani et al., 2014; Vogt et al., 2015; Hirani et al., 2013). This augmented mortality risk may be attributed to the link between vitamin D deficiency and various somatic ailments, with a notable emphasis on cardiovascular disease (Ginde et al., 2009). A study conducted by van den Berg et al. (2016) revealed that in a cohort of elderly individuals aged 60 years and older who were afflicted by depression (n = 367), vitamin D levels exhibited an association with mortality but not with the initiation or remission of depression. Additionally, a study authored by Hirani et al. (2014) demonstrated that both the risk of depression and all-cause mortality correlated with serum 25(OH)D levels below 50 nmol/L. Yu et al. (2023) found that the co-presence of sedentary behavior and vitamin D deficiency was significantly associated with increased all-cause mortality and cancer-specific mortality, and mentioned that it may be based on complex interactions between these variables. Walid et al. (Saliba et al., 2014) found that obesity affects the relationship between 25 (OH)D and mortality. A systematic review featured in JAMA (Kahwati et al., 2021) reported an absence of discernible impacts from vitamin D treatment on mortality rates or the incidence of depression among asymptomatic community residents harboring low vitamin D levels. It is noteworthy, however, that none of the studies included in this review primarily targeted mortality as an outcome. Existing studies are beset by various limitations, including small sample sizes, insufficient control for key covariates, and a lack of specific evaluation of mortality within depressed cohorts. Furthermore, the influence of variables such as smoking, obesity, and antidepressant use on these associations remains uncertain.

To comprehensively address these knowledge gaps, our objective was to conduct a prospective study examining the relationship between serum 25(OH)D concentrations and the risk of all-cause and cause-specific mortality in a nationally representative sample of US adults with depression.

Section snippets
Data sources and study population
The cross-sectional study utilized data from the National Health and Nutrition Examination Survey (NHANES) spanning 2005 to 2018 (National Center for Health Statistics, 2020). NHANES, overseen by the Centers for Disease Control and Prevention, assesses the health and nutritional status of US children and adults, serving as a cornerstone program under the National Center for Health Statistics (NCHS). The study received NCHS Institutional Review Board approval, with participants providing written …

Results
This study extracted data from NHANES 2005–2018, where 70,910 potential participants completed interviews and underwent MEC screening. Participants under 18 years of age, those lacking PHQ-9 scores, and those scoring below 5 points (n = 61,890) were excluded. Subjects with missing serum 25(OH)D data (n = 590) and all-cause mortality data (n = 13) were also excluded. The remaining 8417 participants were included in our analysis, and after weighting, they represent a population of approximately…

Discussion
In a comprehensive prospective cohort study conducted in the United States among adults with depression, we observed a significant inverse association between serum 25(OH)D concentrations and all-cause mortality. This association remained statistically significant after adjusting for various conventional risk factors, including dietary and seasonal variations, BMI, antidepressant medication use, comorbid chronic conditions. Multiple sensitivity and stratified analyses further confirmed the…

Conclusion
In a nationally representative sample in the United States, we observed a significant association between higher serum 25(OH)D concentrations and lower all-cause mortality and cancer-specific mortality among adults with depression. These findings support the potential benefits of maintaining adequate vitamin D status in preventing premature mortality in individuals with depression.


Many References online

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VitaminDWiki - 6 studies in both categories Cardiovascular and Depression

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