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Information on the latest vitamin D news and research.

Find out more information on deficiency, supplementation, sun exposure, and how vitamin D relates to your health.

Animal study: Vitamin D metabolism increased in stress-induced depression

A recent animal study published in Psychoneuroendocrinology found that depression caused by chronic unpredictable mild stress increases the metabolism and concentration of vitamin D in the hippocampus and cardiac muscle.

Chronic unpredictable mild stress (CUMS) is an accepted model of animal depression. In rats, chronic stress leads to depressive behavior, abnormal cardiac function, and exaggerated reactivity to stressors. In humans, the precipitation of depressive episodes have been linked to stressful life events.  There is a positive association between depression and cardiac morbidity and mortality, and depression is recognized as a risk factor for cardiovascular disease (CVD). Individuals with major depression have four times the risk of a heart attack than the general population.

Depressive patients are known to have low vitamin D levels and a recent meta-analysis of a group of studies involving 31,424 total participants found that rates of depression were higher in people with insufficient vitamin D levels compared to those with sufficient levels. Vitamin D deficiency has also been linked to a few different types of CVD.

Over the past several years, the enzymes involved in vitamin D metabolism as well as the vitamin D receptor (VDR) have been identified in not only the kidneys where they were first discovered, but also in the pancreas, heart, brain, and immune system.

Recently, researchers from Central South University in Changsha, China wanted to explore the relationship between vitamin D metabolism, stress-induced depressive behavior, and cardiac dysfunction in rats.

They examined two areas in particular: the hippocampus and the cardiac muscle. The hippocampus is especially vulnerable to stress and the breakdown of the hippocampus due to elevated stress hormones is a main factor in developing depression. They looked at these two areas because past research suggests that vitamin D may help protect the brain and heart tissues from stress-induced damage.

Sixteen rats were randomly assigned to either a group exposed to CUMS, or a control group. Each rat of the CUMS group was exposed to a single stressor daily, and the rats were subjected to multiple stressors over the course of the study. These stressors included 24-hour fasting, 20 minutes of noise, and cage tilting for 24 hours.

After 4 weeks, the rats’ hippocampi and heart muscle were analyzed using a variety of tests that measured VDR levels, levels of CYP27B1 and CYP24A1 (enzymes that activate and eliminate vitamin D, respectively), and local (within the hippocampus) concentrations of activated vitamin D.

The researchers wanted to observe the effects of stress-induced depression on local (within the cells) metabolism of vitamin D in the hippocampus and heart muscle.

Here’s what the analysis of the hippocampus showed:

  • There was a significant increase in CYP27B1 levels in CUMS rats compared to the rats in the control group (p < 0.01).
  • VDR concentration was significantly increased in CUMS rats compared to the rats in the control group (p < 0.01).
  • The levels of local activated vitamin D increased significantly in CUMs rats compared to the rats in the control group.

An analysis of the cardiac muscle showed:

  • Levels of CYP27B1, CYP24A1, and VDR increased significantly in the CUMS group compared to the rats in the control group (p < 0.01).

The researchers also found that serum levels of activated vitamin D were unaffected by the CUMS procedure.

They summarized their results by saying,

“Collectively, the present study demonstrates an elevated expression of CYP27B1/CYP24A1/VDR in the hippocampus and myocardium of CUMS rats which may link [vitamin D] with the progression of stress-induced coexistence of depressed mood and CV dysfunction.”

These results suggest a mechanism by which the brain compensates for stress-induced depression by increasing the levels of VDR and the enzymes needed to activate vitamin D and dispose of it after it has performed the vital function of protecting cells from the damage of excess stress hormones.

Although the study was performed in rats and may not be generalizable to humans, it provides a focus for future studies on humans on preventing and treating the high co-prevalence of depression and CV.


Jiang, P. et al. Stress and vitamin D: altered vitamin D metabolism in both the hippocampus and myocardium of chronic unpredictable mild stress exposed rats. Psychoneuroendocrinology, 2013.

  About: Will Hunter

Will is the Program Associate of the Vitamin D council and works on website administration, content production and editing, and fundraising. He is passionate about nutrition, exercise, and technology and how they relate to health and longevity.