Does Supplementing With Vitamin D Impact Cancer Incidence or Mortality?

By Dr. Erica Rizzolo, ND


 

If you’ve seen a naturopathic doctor before, chances are you know a thing or two about vitamin D! Supplementing with vitamin D is often talked about in the winter months to treat vitamin D deficiency,1 possibly reduce symptoms of depression,2 support our immune system,3,4 and more. If you or someone you love are impacted by cancer, you may be curious to read on about whether vitamin D plays a role in “cancer incidence” and “cancer mortality.”

Please note, words in “quotations” are defined below.

 

 

This blog provides an overview of the paper: Association between vitamin D supplementation and cancer incidence and mortality: A trial sequential meta-analysis of randomized controlled trials

Researchers conducted a type of study called a “meta-analysis.” They designed it to look at whether vitamin D supplements have an impact on “cancer incidence” or “cancer mortality” in adults.5 The analysis included 26 randomized controlled trials (RCTs), with a total of 60,876 participants in the intervention group (i.e., those receiving vitamin D) and 60,653 in the control group (i.e., those not receiving vitamin D).

 

Where did researchers find these studies? Which studies were included or excluded?

Researchers gathered studies from the medical literature by accessing publication databases (PubMed, Scopus and Embase) from inception to February 6th, 2022. The studies included were RCTs conducted in adults (≥ 18) who had a cancer diagnosis and were taking vitamin D (at any dose), with or without calcium. All RCTs included a control group who took a placebo in place of the vitamin D, also with or without calcium. The study outcomes included total and site-specific (e.g., lung, breast, etc.) cancer incidence and total and site-specific cancer mortality. Studies were excluded if they were not placebo controlled RCTs, if they included patients who were pregnant, breastfeeding or critically ill, if the sample size was less than 150, or if the study had a follow-up period of less than 1 year.

 

What was the risk of bias and quality of evidence?

The RCTs were assessed for biases: 18 had a low risk, 8 had an unclear risk, and 0 had a high risk of bias (that’s a good sign!). The quality of evidence was assessed using something called the “GRADE” scale. Unlike the risk of bias which evaluates studies individually, the GRADE scale is applied to a body of evidence. A high quality of evidence was found for the outcomes ‘total cancer incidence’ and ‘total cancer mortality’ that were assessed.Where did researchers find these studies? Which studies were included or excluded?

Researchers gathered studies from the medical literature by accessing publication databases (PubMed, Scopus and Embase) from inception to February 6th, 2022. The studies included were RCTs conducted in adults (≥ 18) who had a cancer diagnosis and were taking vitamin D (at any dose), with or without calcium. All RCTs included a control group who took a placebo in place of the vitamin D, also with or without calcium. The study outcomes included total and site-specific (e.g., lung, breast, etc.) cancer incidence and total and site-specific cancer mortality. Studies were excluded if they were not placebo controlled RCTs, if they included patients who were pregnant, breastfeeding or critically ill, if the sample size was less than 150, or if the study had a follow-up period of less than 1 year.

 

What was the risk of bias and quality of evidence?

The RCTs were assessed for biases: 18 had a low risk, 8 had an unclear risk, and 0 had a high risk of bias (that’s a good sign!). The quality of evidence was assessed using something called the “GRADE” scale. Unlike the risk of bias which evaluates studies individually, the GRADE scale is applied to a body of evidence. A high quality of evidence was found for the outcomes ‘total cancer incidence’ and ‘total cancer mortality’ that were assessed.

 

What were the results?

Researchers found that vitamin D supplementation did in fact reduce cancer mortality. The “risk ratio” (RR) was 0.88 with a 95% “confidence interval” (CI) between 0.8 to 0.96. Vitamin D supplementation did not appear to reduce cancer incidence (RR: 0.98, 95% CI: 0.94 – 1.02). These outcomes were pooled results, meaning when all cancer types were analyzed together.

When looking at specific cancer types, vitamin D supplementation reduced the incidence of hematologic (blood-based) cancers, but there were no significant differences in incidence for lung cancer, breast cancer, colorectal cancer or nonmelanoma skin cancer. As noted above, although the total risk of mortality was reduced, vitamin D supplementation did not reduce the mortality of lung cancer, breast cancer, or colorectal cancer when these cancers were analyzed separately.

The authors also looked at cancer incidence and mortality for different subgroups. A subgroup is a smaller group with defining characteristics. For example, a subgroup analysis was done on those taking a specific dose of vitamin D.

 

A stratified analyses showed a significant correlation between cancer mortality and supplementation with vitamin D in these subgroups:

  • Baseline vitamin D was ≤ 20 ng/mL
  • Attained vitamin D was < 40 ng/mL
  • Vitamin D was taken daily (as opposed to separated larger doses)
  • Daily dose ≤ 2,000 IU
  • Intervention included both vitamin D and calcium
  • Follow-up period ≥ 5 years
  • Publication date before 2016

Although these groups showed a reduction in cancer mortality when supplementing with vitamin D, the analysis did not provide a result considered to be statistically significant (i.e. the correlation could be due to chance at a rate higher than 5%), which is why they are described only as a “significant correlation.”

 

What were the conclusions?

The authors concluded that their meta-analysis suggests that “vitamin D supplementation, compared to placebo with or without calcium, was not associated with a reduction in total cancer incidence, except for hematologic malignancies, but significantly decreased total cancer mortality.” Because of the way the data was analyzed (a “trial sequential meta-analysis”), there was reliable evidence that vitamin D supplementation reduced the risk of cancer mortality by at least 10% and did not alter cancer incidence by 5% or more.

 

Keep in mind

There is high “heterogeneity” (i.e., diversity) across trial doses and forms. This meta-analysis included studies using any dose of vitamin D and did not distinguish between the form of vitamin D administered, meaning patients could have received liquid drops, softgels, or tablets at any dose. This may be important to keep in mind because vitamin D is a fat-soluble vitamin, best absorbed with a high-fat meal, so someone taking softgels in an MCT oil carrier with a snack of nuts and seeds might be absorbing more than someone taking a tablet form of vitamin D away from food. In addition, the authors could not determine if taking a higher dose of vitamin D correlates with a higher reduction in cancer mortality. We won’t know the impact of these factors until more research is done.

 

 

Should everyone supplement with vitamin D?

Supplementing with vitamin D may not be for everyone. There are many factors that impact vitamin D absorption and blood levels, such as our age, weight, and skin colour. NDs like to say, “test don’t guess!”, this is because someone deficient in vitamin D may need a much higher dose compared to someone who has sufficient levels. Talk to a licensed healthcare provider about whether taking vitamin D is right for you.

 


Definitions

 

Cancer incidence: the rate of new cancer cases that develop in a population in a specific time period.

Example: 29,400 Canadian women were diagnosed with breast cancer in 2023. This is different from cancer “prevalence”, which describes the number of people with cancer in a population at a specific time.


Cancer mortality:
deaths caused by cancer.

Example: the death rate of colorectal cancer was 13.1 per 100,000 men and women per year.

 

Confidence interval: the probability that an outcome falls within a set range.

Example: In this study, the 95% confidence interval for cancer mortality was 0.80 – 0.96. This means that, although the risk ratio was calculated to be 0.88, we are 95% confident it’s between 0.80 and 0.96.

 

Heterogeneity: diversity within the group

Example: five studies using 400 IU, 1,000 IU, 500 IU, 800 IU, and 2,500 IU per day has higher heterogeneity compared to an analysis on five studies looking at doses ranging from 1000-2,500 IU per day. 

 

Meta-analysis: A study design where data from a number of different studies of the same subject are examined in order to determine overall trends.

 

Risk ratio: A measure of the risk of a certain event happening in one group compared to another group. A risk ratio of 1.00 means that neither group is more likely to experience an event.

Example: In this study, the risk ratio for cancer mortality was 0.88. This means that, for people supplementing with vitamin D, their risk of dying from cancer is estimated to be 0.88 times the risk of someone who isn’t supplementing with vitamin D. We call this a risk reduction of 12%, meaning they are 12% less likely to experience an event.

 

Trial sequential meta-analysis: a type of meta-analysis that weighs type I (false positive) and type II (false negative) errors in order to tell whether the effect is large enough to be unaffected by future studies. It tells us if the studies are powered well enough to rely on the evaluation of the results.


 

Author: Dr. Erica Rizzolo, ND

Dr. Erica Rizzolo is a licensed naturopathic doctor at The Centre for Health Innovation, where she works with people affected by cancer, as well as other conditions such as anxiety, eating disorders, and Inflammatory Bowel Disease. Erica joined the team at The Patterson Institute for Integrative Oncology Research as a research assistant in 2022 and continues to support research initiatives. She is also a member of the research committee for the Oncology Association of Naturopathic Physicians.


 

 

 

References

  1. Bouillon, R., Manousaki, D., Rosen, C. et al.The health effects of vitamin D supplementation: evidence from human studies. Nat Rev Endocrinol 18, 96–110 (2022). https://doi.org/10.1038/s41574-021-00593-z
  2. Mikola, T., Marx, W., Lane, M. M., Hockey, M., Loughman, A., Rajapolvi, S., … Ruusunen, A. (2023). The effect of vitamin D supplementation on depressive symptoms in adults: A systematic review and meta‐analysis of randomized controlled trials. Critical Reviews in Food Science and Nutrition63(33), 11784–11801. https://doi.org/10.1080/10408398.2022.2096560
  3. Shah K, Varna VP, Sharma U, Mavalankar D. Does vitamin D supplementation reduce COVID-19 severity?: a systematic review. QJM. 2022 Oct 25;115(10):665-672. doi: 10.1093/qjmed/hcac040. PMID: 35166850; PMCID: PMC9383458.
  4. Martineau AR, Jolliffe DA, Hooper RL, Greenberg L, Aloia JF, Bergman P, Dubnov-Raz G, Esposito S, Ganmaa D, Ginde AA, Goodall EC, Grant CC, Griffiths CJ, Janssens W, Laaksi I, Manaseki-Holland S, Mauger D, Murdoch DR, Neale R, Rees JR, Simpson S Jr, Stelmach I, Kumar GT, Urashima M, Camargo CA Jr. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. BMJ. 2017 Feb 15;356:i6583. doi: 10.1136/bmj.i6583. PMID: 28202713; PMCID: PMC5310969.
  5. Guo, Z, Huang M, Fan D, et al. (2022, Oct 30). Association between vitamin D supplementation and cancer incidence and mortality: A trial sequential meta-analysis of randomized controlled trials. 63(26), 8428-8442. from Critical Reviews in Food Science and Nutrition