Recent reviews of clinical evidence confirm a claim that dates back to 1941
After decades of neglect, vitamin D has finally regained long-overdue respect.
That renewed respect for the “sunshine and seafood” vitamin is well-justified, given its key roles in bone, heart, and immune health.
Yet, despite a sharp rise in research on vitamin D and sales of vitamin D supplements, one out of four Americans remain deficient: see Many Americans are Likely to Lack Vitamin D.
Before we get to the results of two new clinical-evidence reviews, which link daily vitamin D supplements to better cancer outcomes, let's quickly review the history.
Vitamin D and cancer risk: History and overview
During the 1940’s, pathology professor Frank Apperly of the Medical College of Virginia was intrigued by evidence that people living in environments or working in occupations linked to a high risk of skin cancer — which is associated with greater sun exposure — were at lower risk for other cancers.
So, he did his own research, which revealed that cancer death rates in Canada and the United States were lower in sunnier southern latitudes and higher in darker northern regions.
Apperly’s landmark finding led to speculation that sunlight protects patients from non-skin cancers because it stimulates internal production of vitamin D.
The results of three major evidence reviews suggest that daily vitamin D pills can reduce the risk of death, albeit modestly (Bolland MJ et al. 2014; Bjelakovic G et al. 2014; Autier P et al. 2017).
And epidemiological evidence supports vitamin D's potential to reduce the risk of getting or dying from cancer. For example, see Vitamin D May Defend Against Breast Cancer, Vitamin D Linked to Lower Colorectal Cancer Risk and their links to related articles.
While we lack conclusive evidence that higher vitamin D levels can prevent cancer, researchers from the universities of Edinburgh and Dublin recently reported growing evidence that vitamin D can improve cancer survival rates and reduce progression of cancer (Vaughan-Shaw PG et al. 2017).
Now, the results of two separate evidence reviews show that people who take vitamin D supplements for at least three years are less likely to die from cancer over the short term.
Two clinical-evidence reviews link vitamin D pills to reduced cancer death risk
These recent reviews of the best clinical evidence looked for links between daily vitamin D supplements to longer cancer survival, and/or to a reduced risk for dying from cancer.
Review #1 – Michigan State team links three years of vitamin D to reduced cancer death risk
For their study, Michigan State University researchers reviewed the evidence from 10 randomized, controlled clinical trials involving 79,055 participants.
The goal was to look for any differences in cancer progression or survival rates between participants who took vitamin D supplements daily and those given placebo pills.
The average participant was 68 years old, 78% were women, and some participants in the trials had cancer when they enrolled, while others did not. Each of the 10 trials included in the review followed its participants for at least four years.
After analyzing the data from the 10 trials, Michigan State researchers calculated that taking supplemental vitamin D for at least three years resulted in a significant 13% reduction in the risk that a cancer patient would die from their disease, compared with cancer patients who took placebo pills.
Importantly, the researchers didn’t find any significant reduction in the risk for developing cancer.
Here’s how lead author Tarek Haykal expressed the meaning of their findings: “Vitamin D had a significant effect on lowering the risk of death among those with cancer, but unfortunately it didn't show any proof that it could protect against getting cancer.”
He added that we still don’t know the daily supplemental dose or blood levels of vitamin D needed to improve cancer survival rates, how it extends the lives of cancer victims, or by how much, on average, vitamin D might extend the lifespans of cancer victims.
As Dr. Haykal said, “There are still many questions and more research is needed. All we can say is that at least three years of taking the supplement is required to see any effect.”
But he would like to see more doctors, especially oncologists, prescribe vitamin D to patients in general: “We know it carries benefits with minimal side effects. There's plenty of potential here.”
Review #2 – U.S./Chinese study links three years of vitamin D to reduced risk of dying from cancer
Scientists from the United States and China collaborated on an analysis of evidence from 52 randomized, controlled clinical trials involving 75,454 participants (Zhang Y et al. 2019).
As in the Michigan State evidence review, some participants in the included trials had cancer when enrolled, while others did not.
While supplemental vitamin D was not linked to a reduction in the risk of death from all causes, vitamin D was linked to a 16% drop in the risk of dying from cancer.
Importantly, the international team’s analysis showed that the risk of death from all causes was slightly but significantly lower in trials with longer follow-up periods.
Similarly, the benefit of reduced risk of dying from cancer was seen only in trials with follow-up periods of three years or longer, not in those with a shorter follow-up.
As the authors said, “According to these findings, supplementation with vitamin D3 for at least three years should be considered.”
Importantly, the US-Chinese team found that vitamin D3 supplements produced a greater reduction in the risk for death from cancer than vitamin D2 supplements.
Likewise, the reduction in risk of death from any cause — while it didn’t reach statistical significance — was greater from vitamin D3 supplements than from vitamin D2 supplements.
Vitamin D3 is the “active” form in the body, which is found primarily in seafood — especially fatty fish like salmon and albacore tuna — while vitamin D2 is found primarily in cheese and in plant foods like mushrooms. Today, most vitamin D supplements contain the D3 form.
The researchers noted that three ongoing trials — the D-Health trial (in Australia), the VIDAL trial (in the UK), and the DO-HEALTH trial (in the UK and Europe) — could corroborate or refute their findings.
Vitamin D sources and requirements
In 2010, an expert committee of the U.S. Institute of Medicine (IOM) established these RDAs and safe intake limits for vitamin D:
- Infants from birth to one year: RDA = 400 IU.
- People aged one to 70 years: RDA = 600 IU.
- People aged 71 or more: RDA = 800 IU.
The Tolerable Upper Intake Level for adults is 4,000 IU per day.
And the IOM recommends a minimum blood level of 20 nanograms per milliliter (ng/mL), which equates to 75 nanomoles per liter (nmol/L).
However, Michael F. Holick, Ph.D., M.D., of Boston University Medical Center agrees with other vitamin D experts that the evidence supports keeping vitamin D levels above 30 ng/mL (75 nmol/L).
Fish fit the vitamin D bill; Sockeye salmon stand out
Fatty fish are the richest food sources of vitamin D by far, providing much more than milk or other D-fortified foods.
Among fish, wild sockeye salmon rank as the richest source, with a single 3.5-ounce serving surpassing the US RDA of 600 IU by about 15 percent:
Vitamin D per 3.5-ounce serving*
• Sockeye salmon – 687 IU
• Albacore tuna – 544 IU
• Silver salmon – 430 IU
• King salmon – 236 IU
• Sardines – 222 IU
• Sablefish – 169 IU
• Halibut – 162 IU
It’s also worth noting that wild salmon have significantly higher levels of vitamin D, compared with farmed salmon: see Wild Salmon Beats Farmed for Vitamin D (Again).
- Apperly FL. The Relation of Solar Radiation to Cancer Mortality in North America. Cancer Res. Cancer Res 1941;1:191–5.
- Autier P, Mullie P, Macacu A, et al. Effect of vitamin D supplementation on non-skeletal disorders: a systematic review of meta-analyses and randomised trials. Lancet Diabetes Endocrinol 2017;5:986-1004. 10.1016/S2213-8587(17)30357-1
- Bertino JR. Landmark Study: The Relation of Solar Radiation to Cancer Mortality in North America. Cancer Res. 2016 Jan 15;76(2):185. doi: 10.1158/0008-5472.CAN-15-3169.
- Bjelakovic G, Gluud LL, Nikolova D, et al. Vitamin D supplementation for prevention of mortality in adults. Cochrane Database Syst Rev 2014;(1):CD007470. 10.1002/14651858.CD007470.pub3
- Bolland MJ, Grey A, Gamble GD, Reid IR. The effect of vitamin D supplementation on skeletal, vascular, or cancer outcomes: a trial sequential meta-analysis. Lancet Diabetes Endocrinol 2014;2:307-20. 10.1016/S2213-8587(13)70212-2
- Centers for Disease Control and Prevention and National Cancer Institute, U.S. Cancer Statistics Working Group, June 2019. Rate of New Cancers: All Types of Cancer, United States, 2016. Accessed at www.cdc.gov/cancer/dataviz
- Samji V et al. Role of vitamin D supplementation for primary prevention of cancer: Meta-analysis of randomized controlled trials. J Clin Oncol, 2019; 37 (15_suppl): 1534 DOI: 10.1200/JCO.2019.37.15_suppl.1534
- Vaughan-Shaw PG, O'Sullivan F, Farrington SM, Theodoratou E, Campbell H, Dunlop MG, Zgaga L. The impact of vitamin D pathway genetic variation and circulating 25-hydroxyvitamin D on cancer outcome: systematic review and meta-analysis. Br J Cancer. 2017 Apr 11;116(8):1092-1110. doi: 10.1038/bjc.2017.44. Epub 2017 Mar 16. Review
- Zhang Y, Fang F, Tang J, Jia L, Feng Y, Xu P, Faramand A. Association between vitamin D supplementation and mortality: systematic review and meta-analysis. BMJ. 2019 Aug 12;366:l4673. doi: 10.1136/bmj.l4673.