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Recent study finds vitamin D supplementation reduces depressive symptoms in chronic liver disease patients

Posted on: August 3, 2015   by  Amber Tovey


A clinical trial published in the most recent edition of the journal Clinical Nutrition found that vitamin D supplementation reduced depressive symptoms in patients with chronic liver disease.

Chronic liver disease (CLD) is a condition characterized by the progressive destruction and regeneration of the liver, which leads to scarring. Chronic denotes that the disease of the liver must have lasted over six months. There are various causes for CLD, including infection, autoimmune disorders, genetic diseases, cancers and alcohol abuse.

Studies have found that vitamin D deficiency is associated with CLD. This association may be in part due to the liver’s vital role in the metabolism of vitamin D. The primary circulating form of vitamin D and the accepted marker of vitamin D status, 25(OH)D, is produced via the liver. Theoretically, individuals with liver failure would have impaired ability to make 25(OH)D but this has never been demonstrated. However, this theoretical fear has driven some physicians to tell their CLD patients not to take vitamin D.

Since vitamin D receptors are located on almost every type of cell in the human body, researchers have found that vitamin D plays a role in many health outcomes outside of its traditional role in bone health. Vitamin D receptors are located in both the liver and the brain; thus, leading researchers to hypothesize that vitamin D may be linked to depression in CLD.

Approximately 30% of CLD patients suffer from depression. Treatment with anti-depressants is not always plausible due to the liver failure and thus severe medication side effects. Thus, alternative treatments warrant further investigation. Researchers recently conducted both a cross-sectional and clinical trial to determine the link between vitamin D and depressive symptoms in CLD patients.

They measured the vitamin D levels of 111 patients with CLD. Depression severity was assessed using the Beck Depression Inventory II (BDI-II) with a higher score indicating a more severe state of depression. The researchers found that 81% of the patients had insufficient vitamin D levels defined by levels less than 30 ng/ml, and 31% showed depressive symptoms. In the cross-sectional analysis, low vitamin D levels were associated with increased severity of depression (p = 0.004).

Then, a total of 77 CLD patients who were vitamin D insufficient were enrolled into the open-label clinical trial. Of these, 24 patients had depression and 53 did not. The patients received 20,000 IU of vitamin D weekly for six months. The researchers reassessed vitamin D status and depression severity after three and six months of treatment. Here is what they found:

  • The mean baseline 25(OH)D in the entire group was 17 ng/ml.
  • After six months of supplementation, the average vitamin D status was 38.2 ng/ml and 35.1 ng/ml in depressed and non-depressed patients, respectively.
  • After three months, BDI-II scores significantly decreased in depressed patients (p = 0.003).
  • After six months, BDI-II scores also significantly decreased in depressed patients (p = 0.004).

The researchers concluded,

“The findings herein support the primary study hypothesis that the correction of vitamin D deficiency ameliorates depressive symptoms in patients with CLD.”

While this analysis yielded interesting findings, its limitations must be noted. First, this study did not include a control group. Therefore, the placebo effect cannot be out ruled as a possible contributor to the positive results. In addition, the clinical trial included patients with and without depression. Vitamin D should not produce any positive effects on depressive symptoms in individuals who do not suffer from depression.

Another interesting finding in this study was the finding that 20,000 IU/week, or about 3,000 IU/day, resulted in raising the mean 25(OH)D levels for 17 ng/ml to the mid to high 30s, about what one would expect. This demonstration that vitamin D is metabolized into 25(OH)D in CLD patients should assuage the fear some physicians have about giving vitamin D to their CLD patients.

Randomized controlled trials of patients with both vitamin D deficiency and CLD are needed to fully understand the effects of vitamin D supplementation on depression in CLD patients.

Citation of article

Tovey, A. & Cannell, J. Recent study finds vitamin D supplementation reduces depressive symptoms in chronic liver disease patients. Vitamin D Council Newsletter, 2015.


Stokes C., et al. Vitamin D supplementation reduces depressive symptoms in patients with chronic liver disease. Clinical Nutrition, 2015.


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