Vitamin D3 Clinical Evidence

The Journal of Environmental Pathology, Toxicology and Oncology
Edlich R, et al. Scientific documentation of the relationship of vitamin D deficiency and the development of cancer. 2009;28(2):133-41. 

Topic: 
Does vitamin D deficiency increase cancer risk?

Background:
It is well-known that vitamin D is important for optimal skeletal growth, yet most physicians do not appreciate the role of vitamin D deficiency in predisposing people to the development of cancer.

Study Type:
Review paper

Results:
The authors present data showing that:

  • Insufficient vitamin D is associated with developing cancer of the colon/rectum, prostate and ovaries, as well as multiple myeloma (a bone marrow cancer).
  • There is an inverse relationship between vitamin D levels and breast cancer incidence. (In other words, the higher a woman’s vitamin D levels, the less likely she is to develop breast cancer and vice versa.)
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Critical Reviews in Clinical Laboratory Sciences 
Gocek E, Studzinski GP. Vitamin D and differentiation in cancer. 2009;46(4):190-209. 

Topic: 
What is the relationship between vitamin D and cell differentiation in cancer?

Background:
One distinguishing feature of cancer cells is that they lack differentiation — i.e. the ability to specialize in specific functions — yet they still have the potential to divide and proliferate.

Study Type:
Review paper

Results:
The authors present data showing that:

  • Review the current understanding of how vitamin D can help tumor cells differentiate into “near-normal” cells.
  • Outline the existing, though fragmentary, knowledge of the signaling pathways that lead colon, breast, prostate, squamous cell carcinoma, osteosarcoma and myeloid leukemia cancer cells to differentiate, thus inhibiting cell proliferation.

Anticancer Research 
Köstner K, et al. The relevance of vitamin D receptor (VDR) gene polymorphisms for cancer: a review of the literature. 2009 Sep;29(9):3511-36. 

Topic: 
Can mutations of the vitamin D receptor (VDR) gene increase the risk of developing various cancers?

Background:
In recent years, the relevance of mutations in the VDR gene to the development of various types of cancer has been investigated by a great number of studies, often showing controversial results.

Study Type:
Review paper

Results:
While the authors acknowledge that “at present, it is still not possible to make any definitive statements about the importance of the VDR genotype for cancer occurrence,” they found the strongest associations between a VDR mutation and increased risk of breast cancer, prostate cancer and malignant melanoma. 

 

Psychopharmocology 
Lansdowne AT, Provost SC. Vitamin D3 enhances mood in healthy subjects during winter. 1998 Feb; 135(4):319-23. 

Topic: 
Can vitamin D3 elevate mood during the winter months?

Background:
Seasonal Affective Disorder (SAD) is a cyclic form of depression that occurs in the fall and winter. Because the body produces vitamin D when the skin is exposed to sunlight, and access to sunshine is limited during the winter months, it has been theorized that SAD may be caused by decreases in vitamin D3 levels. Such decreases may lead to changes in brain serotonin, a neurotransmitter that regulates mood.

Study Type:
Human clinical intervention trial

Study Design:
Randomized, double-blind: Subjects either received vitamin D3 for five days in late winter or nothing. They were instructed to self-report their affect (i.e. record their moods).

Subjects:
44 healthy subjects

Dosage:
400 or 800 IU daily for 5 days

Conclusion:
The authors found vitamin D3 “significantly enhanced positive affect and there was some evidence of reduction in negative affect.”

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American Heart Journal 
May HT, et al. Association of vitamin D levels with incident depression among a general cardiovascular population. 2010;159(6):1037-43. 

Topic: 
Is vitamin D deficiency associated with depression?

Background:
People with cardiovascular disease often also suffer from depression. One contributing factor could be vitamin D deficiency, which may contribute to both depression and cardiovascular events.

Study Type:
Human clinical intervention trial

Study Design:
Vitamin D levels were measured and subjects were divided into four categories: those with optimal, normal, low and very low levels. Subjects were also screened for depression.

Subjects:
7,358 subjects, aged 50 or older with a cardiovascular diagnosis but no prior diagnosis of depression.

Results:
All the groups except the group with optimal vitamin D levels had elevated levels of depression. This was especially true in the winter months, for those over the age of 65, and for men.

Conclusion:
Among a CV population > or =50 years with no history of depression, vitD levels were shown to be associated with incident depression after vitD draw. This study strengthens the hypothesis of the association between vitD and depression.

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Applied Nursing Research 
Shipowick CD, et al. Vitamin D and depressive symptoms in women during the winter: a pilot study. 2009 Aug;22(3):221-5. 

Topic: 
Can vitamin D relieve symptoms of depression in women during the winter?

Background:
Previous studies have shown vitamin D can alleviate symptoms of depression in the winter months. Will this proves true for women, who are more prone to depression than men?

Study Type:
Human clinical intervention trial

Study Design:
Subjects’ vitamin D levels were measured and their depressive symptoms were evaluated using the Beck Depression Inventory, both at the study’s start and again after supplementing with vitamin D.

Subjects:
9 women with vitamin D levels below 40 ng/ml (6 women completed the study)

Results:
Subjects who took vitamin D saw their vitamin D levels rise by an average of 27ng/ml and their score on the depression inventory fall by 10 points.

Conclusion:
This study suggests that supplemental vitamin D3 reduces depressive symptoms.

Journal of Internal Medicine 
Jorde R, et al. Effects of vitamin D supplementation on symptoms of depression in overweight and obese subjects: randomized double blind trial. 2008 Dec;264(6):599-609. 

Topic: 
Can vitamin D alleviate symptoms of depression in overweight and obese subjects?

Background:
Previous studies have demonstrated that vitamin D can relieve symptoms of depression. Overweight and obese people require greater quantities of vitamin D to maintain a healthy level of the hormone in their blood due to their greater body size. Can supplementation help them?

Study Type:
Human clinical intervention trial

Study Design:
Cross-sectional, randomized, double-blind, controlled trial of vitamin D versus placebo for one year. Depressive symptoms were measured using the Beck Depressive Index before and after supplementation.

Subjects:
441 subjects (159 men and 282 women) aged 21-70, with a body mass index between 28-47 (A BMI of 25-30 is classified as overweight; a BMI of 30 or higher is considered obese.)

Dosage:
20,000 or 40,000 IU per week (2,857 – 5,714 IU per day) for 1 year

Results:
Subjects with vitamin D levels less than 40 nmol L(-1) 25(OH)D had significantly more depressive traits (6 versus 4.5) than those with levels at or above 40 nmol L(-1). (Vitamin D deficiency is defined by some experts as a 25(OH)D level below 50 nmol/L.) Those who took vitamin D at either dose significantly improved their scores on the depression index after one year of supplementation. There was no similar improvement among the control group.

Conclusion:
It appears to be a relation between serum levels of 25(OH)D and symptoms of depression. Supplementation with high doses of vitamin D seems to ameliorate these symptoms indicating a possible causal relationship. 

The Journal of Nutrition, Health and Aging 
Gloth FM 3rd, Alam W, Hollis B. Vitamin D vs broad spectrum phototherapy in the treatment of seasonal affective disorder. 1999;3(1):5-7. 

Topic: 
Does vitamin D deficiency contribute to SAD?

Background:
Seasonal Affective Disorder (SAD) is prevalent in the winter, when people’s vitamin D stores run low. Broad-spectrum light therapy helps the skin produce vitamin D. This study compared the efficacy of phototherapy in treating SAD to supplementation with high-dose vitamin D.

Study Type:
Human clinical intervention trial

Study Design:
Randomized, controlled trial. Participants were divided into two: half received vitamin D therapy and half received phototherapy. All of the subjects’ depressive symptoms were evaluated through several scales — the Hamilton Depression scale, the Structured Interview Guide for the Hamilton Depression Rating Scale and the SAD-8 Depression Scale — before and after one month of treatment. Subjects’ vitamin D levels were also measured before and one week after receiving their respective treatments.

Subjects:
15 subjects with SAD

Dosage:
100,000 IU of vitamin D over a one-month period

Results:
Interestingly, while both treatments raised vitamin D levels, all subjects receiving vitamin D improved on all depression tests, while the phototherapy group did not show significant improvement. This may be because vitamin D was more effective (74%) at raising vitamin D levels than phototherapy (36%).

Conclusion:
Improvement in 25-OH D was significantly associated with improvement in depression scales scores…Vitamin D may be an important treatment for SAD.

 

 

Vitamin D3 Mechanism of Action

Vitamin D deficiency has been found in patients with prostate and other cancers. Calcitriol (1,25-dihydroxyvitamin D3), the active form of vitamin D, can stop the growth and division of prostate cancer cells by inducing cell-cycle arrest in stage G1. This means the cancer cell is stopped from dividing while it is still in the early stages of growth. The cell-cycle arrest is accomplished by down-regulating (or decreasing the expression of) a gene called c-Myc, which promotes tumor growth.