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Chronic stress leads to depression but does not affect vitamin D metabolism, says recent study

Posted on: October 29, 2014   by  Will Hunter


Vitamin D deficiency has been repeatedly observed in conditions involving inflammation, such as cardiovascular disease, diabetes, and depression. Researchers are trying to figure out whether vitamin D deficiency causes inflammation or inflammation causes deficiency.

Some evidence shows that chronic inflammation can alter vitamin D metabolism and cause insufficient vitamin D status, while other research supports the hypothesis that vitamin D insufficiency causes and contributes to the inflammation seen in depression and other conditions.

Recent experimental evidence using a rat model supports the latter hypothesis and challenges the idea that vitamin D deficiency is caused by inflammation.

Vitamin D is known to modulate the immune system and inflammation by suppressing proinflammatory cytokines and regulating immune cell activity.

Clinical studies of the effects of vitamin D on various inflammatory diseases have failed to demonstrate significant changes in health outcomes that the observational research hints at.

The contrasting results from epidemiological and intervention studies led to the hypothesis that a deficiency in vitamin D may not actually be the cause of, but instead a result of certain inflammatory disease states.

Clinical researchers from China recently tested the validity of this hypothesis in a model of depression in rats.

Depression is associated with chronic inflammation and it is common for depressed individuals to have increased levels of proinflammatory cytokines. Additionally, depressed individuals have lower vitamin D levels than healthy controls.

To test the aforementioned hypothesis, the researchers selected rats and assigned them to either a control group or a group that underwent chronic mild stress (CMS). CMS is repetitive low-level stress and is the most valid animal model of depression, which means that it accurately represents depression seen in humans.

The rats in the intervention group were exposed to various stressors, including a 45° cage tilt for 24 hours and food deprivation for 24 hours, over the course of eight weeks.

At the end of the eight weeks, the researchers measured vitamin D levels, stress hormones, and proinflammatory cytokine levels of the rats, as well as the expression of two enzymes, CYP27B1 and CYP24A1, responsible for activating and degrading vitamin D, respectively.

They wanted to see if stress-induced depression would cause changes in the expression of these enzymes and if so, whether these changes affected the metabolism of vitamin D and subsequently caused low vitamin D levels.

Their analyses revealed:

  • Rats in the CMS group had significantly increased levels of corticosterone, a hormone that is released in response to stress.
  • Proinflammatory cytokines IL-6, TNF-α, and IFN-γ were all significantly increased in the CMS group.
  • There were no differences in the expression of the either CYP27B1 or CYP24A1 between the two groups.
  • There were no differences in vitamin D or activated vitamin D levels between the two groups.

The researchers concluded,

“In the present study, we found despite the stress procedures caused significant increases in corticosterone and the proinflammatory cytokines levels, the stress-induced chronic neuroendocrine-immune disturbances did not change renal vitamin D metabolism and serum vitamin D status, indicating that the psychological stress and consequent dysregulation in neuroendocrine and immune system may not account for the inadequate vitamin D status in patients with depression.”

They went on to state,

“Hence, combined with the previous large prospective studies that repeatedly substantiated the association between depression and vitamin D deficiency, our findings raise the possibility that hypovitaminosis D precedes the onset of depressed mood.”

The major limitation of this study is the use of an animal model, meaning the results don’t necessarily translate to humans. The researchers also note that the lack of evaluation of other hormones may limit the ability to fully understand the relationship between depression, inflammation and vitamin D.

These results suggest that inflammation does not directly alter the metabolism of vitamin D, as recent research has hinted at. As the researchers mentioned, this may mean that vitamin D deficiency precedes the onset of depression and could contribute to the development of depression and its associated inflammation.

While the results cannot be applied to humans, they can be used to inform and guide future research in humans that examines the effect of inflammatory states on vitamin D metabolism.


Jiang, P. et al. Chronic stress causes neuroendocrine-immune disturbances without affecting renal vitamin D metabolism in rats. Journal of Endocrinological Investigation, 2014.

1 Response to Chronic stress leads to depression but does not affect vitamin D metabolism, says recent study

  1. Ian

    This is a very important result. So much we hear that observational studies are just associations or are “reverse causation”. So much so I often think the objections are “medico-political”. The studies on animals must happen first as they are easier to control and I am confident that more studies will show that vitamin D is a causative variable in so many pathologies given its role in epigenetics and immunology. I look forward to them.

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