Vitamin D

Modest evidencesignificant effects in at least three small but well-designed randomized controlled trials (RCTs), or one or more well-designed, mid-sized clinical studies of reasonably good quality (RCTs or observational studies), or several small studies aggregated into a meta-analysis (this is the CancerChoices definition; other researchers and studies may define this differently) of higher cancer mortality among men without cancer at baseline with 25(OH)D levels above 40 ng/mL (100 nmol/L)

• Higher cancer mortality among men without cancer at baseline with 25(OH)D levels above 40 ng/mL (100 nmol/L) compared to less than 15 ng/mL (37.5 nmol/L) in a very large observationala type of study in which individuals are observed or certain outcomes are measured, but no attempt is made to affect the outcome (for example, no treatment is given); an example is a study that records people’s diets, but doesn’t try to alter their diets, and looks for patterns of disease or other outcomes related to different foods study¹Freedman DM, Looker AC, Abnet CC, Linet MS, Graubard BI. Serum 25-hydroxyvitamin D and cancer mortality in the NHANES III study (1988-2006). Cancer Research. 2010 Nov 1;70(21):8587-97.

Good evidencesignificant effects in one large or several mid-sized and well-designed clinical studies (randomized controlled trials (RCTs) with an appropriate placebo or other strong comparison control or observational studies that control for confounds) (this is the CancerChoices definition; other researchers and studies may define this differently) of moderately higher risk of invasive breast cancer among postmenopausal women with vitamin D intakes higher than 600 IU/day at baseline treated with calcium plus vitamin D

• Moderately higher risk of invasive breast cancer among postmenopausal women with vitamin D intakes higher than 600 IU/day at baseline treated with calcium plus vitamin D compared to placebo in a very large RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects²Cauley JA, Chlebowski RT et al. Calcium plus vitamin D supplementation and health outcomes five years after active intervention ended: the Women’s Health Initiative. Journal of Women’s Health. 2013 Nov;22(11):915-29.

Preliminary evidencesignificant effects in small or poorly designed clinical studies OR conflicting results in adequate studies but a preponderance of evidence of an effect (this is the CancerChoices definition; other researchers and studies may define this differently) of moderately higher colorectal cancer mortality among people with the highest levels of serum vitamin D before cancer diagnosis

• 48% higher colorectal cancer mortality among people with the highest levels of serum vitamin D before cancer diagnosis compared to the lowest levels in a mid-sized observationala type of study in which individuals are observed or certain outcomes are measured, but no attempt is made to affect the outcome (for example, no treatment is given); an example is a study that records people’s diets, but doesn’t try to alter their diets, and looks for patterns of disease or other outcomes related to different foods study³Weinstein SJ, Mondul AM et al. Prediagnostic serum vitamin D, vitamin D binding protein isoforms, and cancer survival. JNCI Cancer Spectrum. 2022 Mar 2;6(2):pkac019.

Good evidencesignificant effects in one large or several mid-sized and well-designed clinical studies (randomized controlled trials (RCTs) with an appropriate placebo or other strong comparison control or observational studies that control for confounds) (this is the CancerChoices definition; other researchers and studies may define this differently) of higher risk of advanced conventional adenomas over an average of about 3 years among people with no history of cancer, 50 years or older for men and 55 years or older for women, and with 25(OH)D levels higher than 30 ng/mL treated with 2000 IU vitamin D3 and 1 g marine omega-3 fatty acids

• Higher risk of advanced conventional adenomas over an average of about 3 years among people with no history of cancer, 50 years or older for men and 55 years or older for women, and with 25(OH)D levels higher than 30 ng/mL treated with 2000 IU vitamin D3 and 1 g marine omega-3 fatty acid per day compared with placebo, but no evidence of an effect on risk among people with serum 25(OH)D levels below 30 ng/mL, in a very large RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects⁴Song M, Lee IM et al. No association between vitamin D supplementation and risk of colorectal adenomas or serrated polyps in a randomized trial. Clinical Gastroenterology and Hepatology. 2021 Jan;19(1):128-135.e6.

Weak evidence of higher risk of colorectal cancer among women treated with estrogen therapy and also treated with 400 IU vitamin D3 plus 1000 mg elemental calcium; see an opposite effect among women not treated with estrogen therapy in How can vitamin D help you? What the research says ›

• A weak trendan apparent change due to a therapy, close to but not achieving full statistical significance (this is the CancerChoices definition; other researchers and studies may define this differently toward higher risk of colorectal cancer among women treated with estrogen therapy and also treated with 400 IU vitamin D3 plus 1000 mg elemental calcium compared to placebo in an analysis of a very large RCT;⁵Ding EL, Mehta S, Fawzi WW, Giovannucci EL. Interaction of estrogen therapy with calcium and vitamin D supplementation on colorectal cancer risk: reanalysis of Women’s Health Initiative randomized trial. International Journal of Cancer. 2008 Apr 15;122(8):1690-4.

Modest evidencesignificant effects in at least three small but well-designed randomized controlled trials (RCTs), or one or more well-designed, mid-sized clinical studies of reasonably good quality (RCTs or observational studies), or several small studies aggregated into a meta-analysis (this is the CancerChoices definition; other researchers and studies may define this differently) of higher risk of adenocarcinoma or squamous cell carcinoma among people with higher 25(OH)D levels

• Higher risk of adenocarcinoma or squamous cell carcinoma among people with higher 25(OH)D levels compared to low levels in a meta-analysisa statistical analysis that combines the results of two or more research studies; the results of smaller research studies addressing the same or similar questions can be analyzed as though they are one bigger, more powerful study of 3 observationala type of study in which individuals are observed or certain outcomes are measured, but no attempt is made to affect the outcome (for example, no treatment is given); an example is a study that records people’s diets, but doesn’t try to alter their diets, and looks for patterns of disease or other outcomes related to different foods studies⁶Zgaga L, O’Sullivan F et al. Markers of vitamin D exposure and esophageal cancer risk: a systematic review and meta-analysis. Cancer Epidemiology, Biomarkers & Prevention. 2016 Jun;25(6):877-86.

Good evidencesignificant effects in one large or several mid-sized and well-designed clinical studies (randomized controlled trials (RCTs) with an appropriate placebo or other strong comparison control or observational studies that control for confounds) (this is the CancerChoices definition; other researchers and studies may define this differently) of higher risk of lung cancer among people with 25(OH)D levels higher than 36 ng/mL compared to mid-range levels

• Higher risk of lung cancer among people with 25(OH)D levels higher than 36 ng/mL compared to mid-range levels (12-32 ng/mL) in a meta-analysisa statistical analysis that combines the results of two or more research studies; the results of smaller research studies addressing the same or similar questions can be analyzed as though they are one bigger, more powerful study of 10 observationala type of study in which individuals are observed or certain outcomes are measured, but no attempt is made to affect the outcome (for example, no treatment is given); an example is a study that records people’s diets, but doesn’t try to alter their diets, and looks for patterns of disease or other outcomes related to different foods studies⁷Chen GC, Zhang ZL et al. Circulating 25-hydroxyvitamin D and risk of lung cancer: a dose-response meta-analysis. Cancer Causes and Control. 2015 Dec;26(12):1719-28.

Modest evidencesignificant effects in at least three small but well-designed randomized controlled trials (RCTs), or one or more well-designed, mid-sized clinical studies of reasonably good quality (RCTs or observational studies), or several small studies aggregated into a meta-analysis (this is the CancerChoices definition; other researchers and studies may define this differently) of higher lung cancer mortality among men without cancer at baseline with 25(OH)D levels higher than 40 ng/mL

• 87% higher lung cancer mortality among men without cancer at baseline with 25(OH)D levels higher than 40 ng/mL (100 nmol/L) compared to levels lower than 20 ng/mL (50 nmol/L), but no evidence of an effectoverall, one or more studies did not demonstrate that a treatment or intervention led to an expected outcome; this does not always mean that there is no effect in clinical practice, but that the studies may have been underpowered (too few participants) or poorly designed. Larger, well-designed studies provide more confidence in making assessments. among women in a very large observationala type of study in which individuals are observed or certain outcomes are measured, but no attempt is made to affect the outcome (for example, no treatment is given); an example is a study that records people’s diets, but doesn’t try to alter their diets, and looks for patterns of disease or other outcomes related to different foods study⁸Freedman DM, Looker AC, Abnet CC, Linet MS, Graubard BI. Serum 25-hydroxyvitamin D and cancer mortality in the NHANES III study (1988-2006). Cancer Research. 2010 Nov 1;70(21):8587-97.

Modest evidencesignificant effects in at least three small but well-designed randomized controlled trials (RCTs), or one or more well-designed, mid-sized clinical studies of reasonably good quality (RCTs or observational studies), or several small studies aggregated into a meta-analysis (this is the CancerChoices definition; other researchers and studies may define this differently) of higher risk of pancreatic cancer among people with high 25(OH)D levels

• More than double the risk of pancreatic cancer among people with 25(OH)D levels of 40 ng/mL (100 nmol/L) or higher compared to levels between 20 and 30 ng/mL (50 and 75 nmol/L) in a large observationala type of study in which individuals are observed or certain outcomes are measured, but no attempt is made to affect the outcome (for example, no treatment is given); an example is a study that records people’s diets, but doesn’t try to alter their diets, and looks for patterns of disease or other outcomes related to different foods study⁹Stolzenberg-Solomon RZ, Jacobs EJ, et al. Circulating 25-hydroxyvitamin D and risk of pancreatic cancer: Cohort Consortium Vitamin D Pooling Project of Rarer Cancers. American Journal of Epidemiology. Jul 1 2010;172(1):81-93.

Weak evidenceone or more case studies, supported by animal evidence OR small treatment effects of limited clinical significance OR studies with no controls OR weak trends of effects (this is the CancerChoices definition; other researchers and studies may define this differently) of higher risk of pancreatic cancer among people with the highest vitamin D intake

• A weak trendan apparent change due to a therapy, close to but not achieving full statistical significance (this is the CancerChoices definition; other researchers and studies may define this differently) toward higher risk of pancreatic cancer among people with the highest vitamin D intake (2 or more times the standard vitamin intake)  compared to the lowest in a meta-analysisa statistical analysis that combines the results of two or more research studies; the results of smaller research studies addressing the same or similar questions can be analyzed as though they are one bigger, more powerful study of 5 observational studies¹⁰Liu Y, Wang X, Sun X, Lu S, Liu S. Vitamin intake and pancreatic cancer risk reduction: a meta-analysis of observational studies. Medicine (Baltimore). 2018 Mar;97(13):e0114.

Good evidencesignificant effects in one large or several mid-sized and well-designed clinical studies (randomized controlled trials (RCTs) with an appropriate placebo or other strong comparison control or observational studies that control for confounds) (this is the CancerChoices definition; other researchers and studies may define this differently) of higher risk of prostate cancer among people with the highest 25(OH)D levels—higher than about 35 ng/ml (87 nmol/L)—in many studies

• 17% higher risk of prostate cancer among people with higher 25(OH)D levels compared to lower levels in a large meta-analysisa statistical analysis that combines the results of two or more research studies; the results of smaller research studies addressing the same or similar questions can be analyzed as though they are one bigger, more powerful study of 21 observationala type of study in which individuals are observed or certain outcomes are measured, but no attempt is made to affect the outcome (for example, no treatment is given); an example is a study that records people’s diets, but doesn’t try to alter their diets, and looks for patterns of disease or other outcomes related to different foods studies¹¹Xu Y, Shao X et al. Positive association between circulating 25-hydroxyvitamin D levels and prostate cancer risk: new findings from an updated meta-analysis. Journal of Cancer Research and Clinical Oncology. 2014 Sep;140(9):1465-77.
• U-shaped associations of vitamin D with risks of total and Gleason 2-6, 7-10 and 8-10 cancers, so that people with 25(OH)D levels between roughly 20 and 30 ng/mL (50 to 75 nmol/L) had lower risk of cancer compared to people with the lowest or the highest levels, and more strongly for high-grade disease,  in a very large observational study¹²Kristal AR, Till C et al. Plasma vitamin D and prostate cancer risk: results from the Selenium and Vitamin E Cancer Prevention Trial. Cancer Epidemiology, Biomarkers and Prevention. 2014 Aug;23(8):1494-504.
• Weak trendsan apparent change due to a therapy, close to but not achieving full statistical significance (this is the CancerChoices definition; other researchers and studies may define this differently) toward higher risk of prostate cancer among people with each 1,000 IU increase in dietary intake of vitamin D (6 studies) or each 10 ng/mL increase in 25(OH)D levels (14 studies) in meta-analyses of observational studies¹³Gilbert R, Martin RM e tal. Associations of circulating and dietary vitamin D with prostate cancer risk: a systematic review and dose-response meta-analysis. Cancer Causes and Control. 2011 Mar;22(3):319-40.

Weak evidenceone or more case studies, supported by animal evidence OR small treatment effects of limited clinical significance OR studies with no controls OR weak trends of effects (this is the CancerChoices definition; other researchers and studies may define this differently) of higher risk of prostate cancer among people with higher dietary intake of vitamin D

• A weak trend toward higher risk of prostate cancer among people with higher dietary intake of vitamin D compared to low intake in a meta-analysis of 5 observational studies¹⁴Huncharek M, Muscat J, Kupelnick B. Dairy products, dietary calcium and vitamin D intake as risk factors for prostate cancer: a meta-analysis of 26,769 cases from 45 observational studies. Nutrition and Cancer. 2008;60(4):421-41.

Skin cancer has a known link to sun and other ultraviolet (UV) radiation exposure (see Creating a Healing Environment › ), and so benefits of vitamin D from sun exposure may be outweighed by increased risk from the UV radiation. The Vitamin D Council advises that fifteen minutes (for a person with light skin) to a couple of hours (for a person with very dark skin) in the summer midday sun in swimwear three times a week is sufficient sun exposure for vitamin D.¹⁵Barrell A. How to get more vitamin D from the sun. Medical News Today. January 21, 2021. Viewed August 1, 2022;  McNeill AM. Wesner E. Sun protection and vitamin D. Skin Cancer Foundation. May 14, 2018. Viewed August 1, 2022. Further sun exposure does not add vitamin D benefit.

• Moderately higher risks of melanoma (42% higher risk, 6 studies), keratinocyte cancer (30% higher, 8 studies), basal cell carcinomas (41% higher, 4 studies), but no evidence of an effect on squamous cell carcinomas (3 studies) for each 12 ng/mL (30 nmol/L) increase in 25(OH)D levels in a meta-analysisa statistical analysis that combines the results of two or more research studies; the results of smaller research studies addressing the same or similar questions can be analyzed as though they are one bigger, more powerful study of observationala type of study in which individuals are observed or certain outcomes are measured, but no attempt is made to affect the outcome (for example, no treatment is given); an example is a study that records people’s diets, but doesn’t try to alter their diets, and looks for patterns of disease or other outcomes related to different foods studies; the authors acknowledge that these results are “most likely confounded by sun exposure”¹⁶Mahamat-Saleh Y, Aune D, Schlesinger S. 25-hydroxyvitamin D status, vitamin D intake, and skin cancer risk: a systematic review and dose-response meta-analysis of prospective studies. Scientific Reports. 2020 Aug 4;10(1):13151.
• A weak trendan apparent change due to a therapy, close to but not achieving full statistical significance (this is the CancerChoices definition; other researchers and studies may define this differently toward slightly higher risk of melanoma for each 100 IU increase in vitamin D intake from diet, but no evidence of an effect from increased intake from supplements in meta-analyses of 3 observational studies¹⁷Mahamat-Saleh Y, Aune D, Schlesinger S. 25-hydroxyvitamin D status, vitamin D intake, and skin cancer risk: a systematic review and dose-response meta-analysis of prospective studies. Scientific Reports. 2020 Aug 4;10(1):13151.
• A slightly higher risk of basal cell carcinomas for each 100 IU increase in vitamin D intake from diet (3 studies), from supplements (2 studies), or total intake (2 studies) in meta-analyses of observational studies¹⁸Mahamat-Saleh Y, Aune D, Schlesinger S. 25-hydroxyvitamin D status, vitamin D intake, and skin cancer risk: a systematic review and dose-response meta-analysis of prospective studies. Scientific Reports. 2020 Aug 4;10(1):13151.

• 6% higher risk of cardiovascular disease mortality among postmenopausal women treated with 1000 mg calcium carbonate (400 mg of elemental calcium) and 400 IU of vitamin D3 daily compared to placebo in a very large RCT;²⁷Thomson CA, Aragaki AK et al. Long-term effect of randomization to calcium and vitamin d supplementation on health in older women: postintervention follow-up of a randomized clinical trial. Annals of Internal Medicine. 2024 Mar 12. also see results from the same study finding lower risk of breast cancer mortality with use of calcium and vitamin D in How can vitamin D help you? What the research says ›

• Higher markers of inflammation (IL-10 and TNF-α), higher fasting blood glucose, and worse 30-second sit-to-stand test performance during participation in progressive resistance training 2–3 days per week among adults aged 50–75 years with overweight or obesity and with type 2 diabetes treated with 20 g whey protein each morning plus 20 g postexercise and 2000 IU vitamin D₃ per day for 24 weeks compared to no supplementation in a mid-sized RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects²⁸Miller EG, Nowson CA et al. Effects of whey protein plus vitamin D supplementation combined with progressive resistance training on glycaemic control, body composition, muscle function and cardiometabolic risk factors in middle-aged and older overweight/obese adults with type 2 diabetes: a 24-week randomized controlled trial. Diabetes, Obesity and Metabolism. 2021 Apr;23(4):938-949.