Study: Vitamin D levels associated with depressive symptoms

By Nikki Hancocks

- Last updated on GMT

Getty | Marcos Calvo
Getty | Marcos Calvo

Related tags Vitamin d Vitamin d deficiency Depression

A large community sample study has found vitamin D levels are associated with depressive symptomatology due to the vitamin's impact on three specific inflammatory markers.

Whilst there have been some inconsistent results from previous studies, meta-analyses​ and systematic reviews​ indicate that depression may be related to low serum vitamin D concentrations. Previous studies have also indicated an association between depressive symptoms and low-grade inflammatory response​ while a decrease in pro-inflammatory markers has been observed after treatment with anti-depressants and it has been reported​ that inflammation can be a risk factor for the development of depression.

Yet there are few studies examining the complex relationship of vitamin D, depression and inflammation and those that have been conducted are mostly in small samples and with differing methodology. Therefore, the purpose of this study was to examine whether inflammation acts as a moderator or mediator on the association between vitamin D and depressive symptomatology in a large community sample.

The researchers, from the University of Leipzig, Germany, found negative correlations between vitamin D levels and depressive symptomatology and three inflammatory markers (CRP, IL-6, WBC), which were in turn positively associated with depressive symptomatology.

This is the first work examining the role of inflammation in the relation between depressive symptomatology and serum vitamin D levels using mediation and moderation analyses in a community sample.

Due to the cross-sectional design of this study, no assumptions regarding causality can be drawn. 

The report states: "This present work highlighted the complex relationship between vitamin D, depressive symptoms and inflammation...

"In the future, longitudinal and prospective studies should examine changes in inflammation and depressive symptoms, as well as the effect of vitamin D supplementation on inflammation and depressive symptomatology for causality assessment. This might help to shed a new light on the potential role of vitamin D supplementation as an anti-inflammatory therapy option for depression among individuals with low vitamin D levels."


This study analysed data obtained during the research project ‘LIFE’ (Leipzig Research Center for Civilisation Diseases, Germany), which consisted of 10,000 participants (aged 18-80) recruited between August 2011 and November 2014.

Several standardised interviews were performed in order to collect medical history and sociodemographic characteristics. Physical and medical examinations as well as lab tests were conducted and data sets of those who had given a blood sample for the determination of vitamin D and three inflammation markers were retrieved from the LIFE database (n = 9640).

All participants went through a structured interview to assess information on medical history, sociodemographic and socioeconomic data and current medication as well as alcohol and tobacco consumption. A multidimensional index of socioeconomic status was calculated by using the information on education, equivalent household income and occupational status. Body weight and height were also assessed.

The levels of depressive symptomatology within the last week were assessed via the German version of CES-D​ (a structured self-report scale with 20 items).

The happy vitamin

Several potential mechanisms have been proposed to explain the role of vitamin D in the pathophysiology of depression: first, the presence and distribution of vitamin D receptors and the enzyme 1 α-hydroxylase​ (catalyzes conversion of 25(OH)D to 1,25-dihydroxycholecalciferol (1,25(OH)2D)) within brain regions such as hypothalamus, prefrontal cortex, substantia nigra, amygdala and thalamus support the hypothesis that vitamin D could affect the brain. Furthermore, the presence of vitamin D receptor in several neurons and microglial cells indicates the role of vitamin D in immune responses in central nervous system.

Second, there is evidence on the neuroprotective and neurotrophic effect of vitamin D on brain function​, whereas an imbalance between neurodegenerative and neuroprotective markers had been suggested to play a critical role in the pathophysiology of depression​.

Third, it has been shown that 1,25(OH)2D—the active form of vitamin D in the human body—can transcriptionally activate tryptophan hydroxylase 2​ and thereby increase serotonin synthesis, which was found to be altered in depression.

Fourth, studies indicate the modulatory role of vitamin D in adaptive and innate immune systems via multiple mechanisms such as regulating cytokine secretion as well as cell signaling pathways​. 

Source: Nutrients

Dogan-Sander, E.; Mergl, R.; Willenberg, A.; Baber, R.; Wirkner, K.; Riedel-Heller, S.G.; Röhr, S.; Schmidt, F.M.; Schomerus, G.; Sander, C. 

"Inflammation and the Association of Vitamin D and Depressive Symptomatology"

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