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Vitamin D and Cancer

Vitamin D has long been known as a key vitamin in supporting our bone health by aiding the absorption of calcium [1]. Recent studies have also suggested that vitamin D may play a role in influencing our immunity [2]. Read on to find out more about a recently published large-scale trial that investigated the effects of vitamin D supplementation on the risk of cancer.

What is Vitamin D?

Vitamin D, also known as calciferol, is a naturally occurring fat-soluble vitamin in our body. It is produced in our bodies when we are exposed to ultraviolet (UV) rays and can also be found in foods and supplements. Vitamin D undergoes a 2-step activation process to become fully activated in our body, first by the liver and then by the kidneys [1]. It ranks among one of the most widely used supplements, especially in older adults for bone health [3].

The VITAL Trial

The VITamin D and OmegA-3 TriaL (VITAL) trial was a randomized clinical trial that aimed to investigate the effects of vitamin D and omega-3 fish oil supplementations on cancerand cardiovascular diseases (CVD) prevention [4].

The authors also conducted a meta-analysis of the current trials relating to vitamin D together with the VITAL trial to further observe the effects of vitamin D supplementation on cancer and CVD endpoints.

Results from the VITAL trial

The VITAL trial found that vitamin D showed a promising signal for reducing cancer mortality. Although vitamin D did not reduce total overall cancer incidence, subgroup analyses discovered that individuals with normal body mass index (BMI) had a significant reduction in cancer risk. African Americans also had a potential signal in cancer risk reduction as well.

This result also corroborated with earlier trials such as the Randomized Evaluation of Calcium or vitamin D (RECORD) trial [5], which suggested vitamin D supplementation had stronger benefits for cancer mortality than for cancer incidence.

A secondary analysis of the VITAL trial was done to investigate whether vitamin D supplementation can reduce the risk of developing advanced (defined as metastatic or fatal) cancers [6]. The analysis studied the following endpoints:

  • Metastatic and/or fatal cancer
  • Time from baseline to development of metastatic and/or fatal cancer

There was a significant reduction in the risk of developing advanced cancers in patients taking vitamin D compared to the placebo group. Subgroup analysis also found that similar significant effects were only found in participants with normal BMI and not in those who are overweight or obese.

Possible Mechanisms of How Vitamin D Affects Cancer

Laboratory studies have shown that the active form of vitamin D (calcitriol) is involved in multiple cell-signaling pathways, including those responsible for cell division, inflammation, angiogenesis (formation of new blood vessels by the cancer cells) and metastasis (migration of cancer cells) [7].

Other lab studies also found that vitamin D could induce apoptosis (programmed cell death), suggesting a possible role in affecting cancer outcomes [8].

Other Benefits of Vitamin D

Immune Health and COVID-19

Vitamin D has been shown to modulate immune responses, as vitamin D receptors are present on immune cells [2]. Other than being associated with upper respiratory tract infections (URTI) [9] and autoimmune diseases like inflammatory bowel diseases (IBD) [10], low levels of vitamin D may increase the risk of COVID-19 infection and severe disease [11].

Bone Health

Vitamin D increases the absorption of calcium in the gut, which keeps our bones strong [1]. It has been found in several studies that deficiency in vitamin D may lead to loss of bone density. This can result in several diseases such as osteoporosis, rickets (in children), and osteomalacia (in adults) [12].


Apart from improving bone health, recent studies have suggested that vitamin D also affects other bodily systems and diseases, including cancer, immune health and COVID-19. The VITAL trial and the subsequent secondary analysis have also shown that vitamin D reduces the risk of developing advanced cancer in patients without a diagnosis of cancer at baseline. All these suggest the importance of having sufficient vitamin D supplementation.

Related Articles

Vitamin D: Role in COVID-19 Protection and Other Benefits


  1. National Institutes of Health (NIH), Office of Dietary Supplements. Vitamin D. 2021 Aug.
  2. Aranow C. Vitamin D and the immune system. J Investig Med. 2011;59(6):881-886.
  3. Gahche JJ, Bailey RL, Potischman N, Dwyer JT. Dietary Supplement Use Was Very High among Older Adults in the United States in 2011-2014. J Nutr. 2017 Oct;147(10):1968-1976.
  4. Manson JE, Bassuk SS, Buring JE; VITAL Research Group. Principal results of the VITamin D and OmegA-3 TriaL (VITAL) and updated meta-analyses of relevant vitamin D trials. J Steroid Biochem Mol Biol. 2020 Apr;198:105522.
  5. Avenell A, MacLennan GS, Jenkinson DJ, et al.; RECORD Trial Group. Long-term follow-up for mortality and cancer in a randomized placebo-controlled trial of vitamin D(3) and/or calcium (RECORD trial). J Clin Endocrinol Metab. 2012 Feb;97(2):614-22.
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  8. Díaz GD, Paraskeva C, Thomas MG, et al. Apoptosis is induced by the active metabolite of vitamin D3 and its analogue EB1089 in colorectal adenoma and carcinoma cells: possible implications for prevention and therapy. Cancer Res. 2000 Apr 15;60(8):2304-12.
  9. Ginde AA, Mansbach JM, Camargo CA Jr. Association between serum 25-hydroxyvitamin D level and upper respiratory tract infection in the Third National Health and Nutrition Examination Survey. Arch Intern Med. 2009 Feb 23;169(4):384-90.
  10. Adorini L. Intervention in autoimmunity: the potential of vitamin D receptor agonists. Cell Immunol. 2005 Feb;233(2):115-24.
  11. Kaya MO, Pamukçu E, Yakar B. The role of vitamin D deficiency on COVID-19: a systematic review and meta-analysis of observational studies. Epidemiol Health. 2021;43:e2021074.
  12. Vitamin D Deficiency. 2021 Sep.
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