Vitamin D
Vitamin D is a hormone created by the body when skin is exposed to ultraviolet rays in sunlight. It is found naturally in a small number of foods and can also be taken as a fat-soluble dietary supplement.
How can Vitamin D help you? What the research says
We summarize the clinical evidence for each medical benefit here. We begin with our assessment of the strength of evidence within each category, followed by a brief summary of individual studies or reviews of several studies. In assessing the strength of evidence, we consider the study design, number of participants, and the size of the treatment effect (how much outcomes changed with treatment).
To see more details, click the plus sign to the right of any section.
Our assessments of evidence for each medical benefit fall into one of these categories:
- Strong evidence: consistent, significant effects in several large (or at least one very large) well designed clinical studies or at least two meta-analysesa 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 clinical studies of moderate or better quality (or one large meta-analysis) finding similar results
- Good evidence: significant effects in one large or several mid-sized and well-designed clinical studies ( randomized controlled trialsa 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 effects with an appropriate placebo or other strong comparison control or observational studies that control for confounds)
- Modest evidence: significant 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 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), or several small studies aggregated into a meta-analysis
- Preliminary evidence: significant effects in small or poorly designed clinical studies OR conflicting results in adequate studies but a preponderance of evidence of an effect
- Weak evidence: one 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
- Insufficient evidence: preclinical evidence only OR clinical studies with such poor or unclear methodology that no conclusion can be drawn OR conflicting findings across clinical studies with no preponderance of evidence in one direction; conflicting evidence occurs when studies find conflicting effects (positive effect vs no effect or negative effect) with the same treatment and the same general study population (same cancer type, for example)
Learn more about how we research and rate therapies and practices in How We Rate Therapies ›
Vitamin D levels in blood or plasma are typically reported as 25-hydroxyvitamin D levels, or 25(OH)D for short. Sometimes researchers don’t report the specific measure used, and so we’ll say only “vitamin D levels” in our statement.
Blood levels
Some research has found that vitamin D in the body reaches an optimum level somewhere between 30 and below 40 ng/mL (75 and 100 nmol/L), as reported on this page. Higher levels than that are not always better and may even carry risks. See Safety and precautions ›
Many people are deficient in vitamin D, with blood levels below about 8 ng/mL (20 nmol/L). An optimal blood level is a better indicator of health benefits than your daily or weekly intake of supplements. In fact, if you have blood levels at or above the optimum range, supplements may bring little benefit. Your vitamin D blood level is a key piece of information for deciding whether and how much supplementation you may need.
Optimizing Vitamin D Levels for Better Cancer Outcomes
CancerChoices Lead Researcher Nancy Hepp discusses how optimal vitamin D levels may help reduce risk, improve cancer outcomes, and manage side effects of treatment. She also discusses how to maintain optimal blood levels of vitamin D.
Play videoGenetic variants
Several variants in our genetics influence the response of our vitamin D receptors and bodies to treatment with vitamin D. Research regarding the impacts of genetic variants on vitamin D treatment among people with or at risk of cancer is summarized in Are you a health professional? ›
Improving treatment outcomes
Is vitamin D linked to improved survival? Is it linked to less cancer growth or metastasis? Does it enhance the anticancer action of other treatments or therapies? We present the evidence.
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 better cancer-specific survival among people with cancer with high vitamin D levels
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 lower overall mortality among people with cancer taking vitamin D supplements
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 lower cancer-specific mortality 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. on relapse among people with cancer using vitamin D supplements after diagnosis
Vitamin D levels: good evidence of moderately better cancer-specific survival among people with cancer with high vitamin D levels
- Moderately better cancer-specific survival among people with cancer with high 25(OH)D levels compared to low 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 49 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 studies1Vaughan-Shaw PG, O’Sullivan F et al. The impact of vitamin D pathway genetic variation and circulating 25-hydroxyvitamin D on cancer outcome: systematic review and meta-analysis. British Journal of Cancer. 2017 Apr 11;116(8):1092-1110.
Vitamin D supplements
Modest evidence of lower overall mortality among people with cancer taking vitamin D supplements
Weak evidence of lower cancer-specific mortality among people with cancer using vitamin D supplements after diagnosis
- Lower overall mortality among people with cancer taking vitamin D supplements compared to no vitamin D supplements in a meta-analysis of 3 observational studies and 2 RCTsrandomized 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 effects2Kanellopoulou A, Riza E, Samoli E, Benetou V. Dietary supplement use after cancer diagnosis in relation to total mortality, cancer mortality and recurrence: a systematic review and meta-analysis. Nutrition and Cancer. 2021;73(1):16-30.
- Lower overall mortality (9 studies), and a weak trend toward lower cancer-specific mortality (3 studies), a very weak trend toward better progression-free survival (8 studies), but no evidence of an effect on relapse (3 studies) among people with cancer using vitamin D supplements after diagnosis compared with no vitamin D supplements in a meta-analysis of 5 RCTs and 6 observational studies3Chen QY, Kim S et al. Post-diagnosis vitamin D supplement use and survival among cancer patients: a meta-analysis. Nutrients. 2022 Aug 19;14(16):3418.
Modest evidence of better progression-free survival and moderately lower overall mortality among people with advanced or metastatic colorectal cancer with the highest 25(OH)D levels
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 better progression-free survival but no evidence of an effect on tumor objective response ratepercentage of patients whose disease decreased after treatment or overall survival among people with advanced or metastatic colorectal cancer treated with high-dose vitamin D3 during treatment with mFOLFOX6 plus bevacizumab chemotherapy
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 higher objective response rate and better progression-free survival during anti-PD-1 immunotherapy among people with advanced melanoma with normal baseline vitamin D levels or a normal level obtained with supplementation
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. on progression-free survivalthe time during and after treatment of a disease that a patient lives without disease progression (worsening) or overall mortality among people with advanced pancreatic cancer with high 25(OH)D levels
Weak evidence of tumor response among people with metastatic hormone-refractory prostate cancer treated with vitamin D during treatment with docetaxel
Vitamin D levels
Modest evidence of better progression-free survival and moderately lower overall mortality among people with advanced or metastatic colorectal cancer with the highest 25(OH)D levels
Preliminary evidence of higher objective response rate and better progression-free survival during anti-PD-1 immunotherapy among people with advanced melanoma with normal baseline vitamin D levels or a normal level obtained with supplementation
No evidence of an effect on progression-free survival or overall mortality among people with advanced pancreatic cancer with high 25(OH)D levels
- Better progression-free survival and 34% lower overall mortality among people with previously untreated advanced or metastatic colorectal cancer with the highest 25(OH)D levels compared to the lowest 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 study4Yuan C, Sato K et al. Plasma 25-hydroxyvitamin D levels and survival in patients with advanced or metastatic colorectal cancer: findings from CALGB/SWOG 80405 (Alliance). Clinical Cancer Research. 2019 Dec 15;25(24):7497-7505.
- Higher objective response rate and better progression-free survival during anti-PD-1 immunotherapy (nivolumab or pembrolizumab) among people with advanced melanoma with normal baseline vitamin D levels or a normal level obtained with supplementation compared to low levels in a mid-sized observational study5Galus Ł, Michalak M et al. Vitamin D supplementation increases objective response rate and prolongs progression-free time in patients with advanced melanoma undergoing anti-PD1 therapy. Cancer. 2023 Apr 24.
- No evidence of an effect on progression-free survival or overall mortality among people with advanced pancreatic cancer with high 25(OH)D levels compared to low in a mid-sized observational study6Van Loon K, Owzar K et al; Alliance for Clinical Trials in Oncology. 25-Hydroxyvitamin D levels and survival in advanced pancreatic cancer: findings from CALGB 80303 (Alliance). Journal of the National Cancer Institute. 2014 Aug 6;106(8):dju185.
Vitamin D intake
Weak evidence of better progression-free survival but no evidence of an effect on tumor objective response rate or overall survival among people with advanced or metastatic colorectal cancer treated with high-dose vitamin D3 during treatment with mFOLFOX6 plus bevacizumab chemotherapy
Weak evidence of tumor response among people with metastatic hormone-refractory prostate cancer treated with vitamin D during treatment with docetaxel
- 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 better progression-free survival, but no evidence of an effect on tumor objective response rate or overall survival among people with advanced or metastatic colorectal cancer treated with mFOLFOX6 plus bevacizumab and also high-dose vitamin D3 compared to standard-dose vitamin D3 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 effects7Ng K,Nimeiri HS et al. Effect of high-dose vs standard-dose vitamin D3 supplementation on progression-free survival among patients with advanced or metastatic colorectal cancer: the SUNSHINE randomized clinical trial. Journal of the American Medical Association. 2019 Apr 9;321(14):1370-1379.
- Response in prostate-specific antigen (PSA) level among 8 of 26 people (31%) and stable PSA level for 12 weeks or longer among 7 (27%) after failed first-line treatment with docetaxel among people with metastatic hormone-refractory prostate cancer treated with 32 µg oral vitamin D (calcitriol) as 0.5 µg tablets on day 1 of each week and 30 mg/m2 intravenous docetaxel on day 2 for 6 weeks followed by a 2-week rest interval for a maximum of 24 cycles in a small uncontrolled triala study in which a therapy is used, but without a comparison group against which to judge outcomes; an uncontrolled trial is considered a weak study design8Petrioli R, Pascucci A et al. Weekly high dose calcitriol and docetaxel in patients with metastatic hormone-refractory prostate cancer previously exposed to docetaxel. British Journal of Urology International 2007 Oct;100(4):775-9.
Good evidence of lower mortality, less cancer progression, and better rates of pathologic complete response among people with breast cancer with higher 25(OH)D levels
Preliminary evidence of better survival among people with breast cancer taking vitamin D supplements
Preliminary evidence of less tumor blood vessel formation (angiogenesis) during tamoxifen treatment among premenopausal women, but varied results for postmenopausal women treated with vitamin D
No evidence of an effect on markers of tumor proliferation or cell death in primary breast cancer cells from newly diagnosed people treated with 40,000 IU vitamin D daily for 2 to 6 weeks in a small study
Vitamin D levels: good evidence of lower mortality, less cancer progression, and better rates of pathologic complete response among people with breast cancer with higher 25(OH)D levels
- 33% lower overall mortality, with increasing benefit with increasing levels, among people with breast cancer with the highest circulating 25(OH)D levels 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 6 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 of high quality9Hu K, Callen DF, Li J, Zheng H. Circulating vitamin D and overall survival in breast cancer patients: a dose-response meta-analysis of cohort studies. Integrative Cancer Therapies. 2018 Jun;17(2):217-225.
- 25% lower cancer-specific mortality among people with breast cancer with high 25(OH)D levels compared to low levels in a meta-analysis of 8 observational studies10Vaughan-Shaw PG, O’Sullivan F et al. The impact of vitamin D pathway genetic variation and circulating 25-hydroxyvitamin D on cancer outcome: systematic review and meta-analysis. British Journal of Cancer. 2017 Apr 11;116(8):1092-1110.
- Moderately less cancer progression among people with breast cancer with high 25(OH)D levels compared to low levels in a meta-analysis of 8 observational studies11Vaughan-Shaw PG, O’Sullivan F et al. The impact of vitamin D pathway genetic variation and circulating 25-hydroxyvitamin D on cancer outcome: systematic review and meta-analysis. British Journal of Cancer. 2017 Apr 11;116(8):1092-1110.
- 35% lower cancer-specific mortality (4 studies) and 37% lower overall mortality (6 studies) among women with breast cancer with the highest levels of 25(OH)D levels at diagnosis compared to the lowest in meta-analyses of observational studies12Li M, Chen P et al. Review: the impacts of circulating 25-hydroxyvitamin D levels on cancer patient outcomes: a systematic review and meta-analysis. Journal of Clinical Endocrinology and Metabolism. 2014 Jul;99(7):2327-36.
- 38% lower cancer-specific mortality and 42% lower overall mortality among people with breast cancer with higher 25(OH)D levels compared to the lowest in a meta-analysis of 5 observational studies13Maalmi H, Ordóñez-Mena JM, Schöttker B, Brenner H. Serum 25-hydroxyvitamin D levels and survival in colorectal and breast cancer patients: systematic review and meta-analysis of prospective cohort studies. European Journal of Cancer. 2014 May;50(8):1510-21.
- 44% better cancer-specific survival and 57% better overall survival among women with breast cancer with the highest 25(OH)D levels compared to the lowest in a meta-analysis of 12 observational studies14Li C, Li H, Zhong H, Li X. Association of 25-hydroxyvitamin D level with survival outcomes in female breast cancer patients: a meta-analysis. Journal of Steroid Biochemistry and Molecular Biology. 2021 Sep;212:105947.
- 42% lower cancer-specific mortality and 39% lower overall mortality among people with breast cancer with 25(OH)D levels of 29.1 ng/mL or higher compared to lower levels in a meta-analysis of 6 observational studies15Kim Y, Je Y. Vitamin D intake, blood 25(OH)D levels, and breast cancer risk or mortality: a meta-analysis. British Journal of Cancer. 2014 May 27;110(11):2772-84.
- Substantially higher (2.68 times higher) lack of a pathologic complete response among women with breast cancer undergoing initial chemotherapy with 25(OH)D levels less than 20 ng/mL compared to higher levels in a mid-sized observational study16Chiba A, Raman R et al. Serum vitamin D levels affect pathologic complete response in patients undergoing neoadjuvant systemic therapy for operable breast cancer. Clinics in Breast Cancer. 2017 Dec 11. pii: S1526-8209(17)30324-5.
- 22% lower cancer-specific mortality and 27% lower overall mortality across almost 10 years among people with breast cancer with 25(OH)D levels of 30 ng/mL or higher compared to less than 20 ng/mL at the time of diagnosis in a large observational study17Yao S, Sheng H et al. Clinically sufficient vitamin D levels at breast cancer diagnosis and survival outcomes in a prospective cohort of 3,995 patients after a median follow-up of 10 years. Poster presentation at the ASCO 2021 Annual Meeting. Viewed July 1, 2022.
Vitamin D intake
Preliminary evidence of better survival among people with breast cancer taking vitamin D supplements
Preliminary evidence of less tumor blood vessel formation (angiogenesis) during tamoxifen treatment among premenopausal women, but varied results for postmenopausal women treated with vitamin D
No evidence of an effect on markers of tumor proliferation or cell death in primary breast cancer cells from newly diagnosed people treated with 40,000 IU vitamin D daily for 2 to 6 weeks in a small study
- 15% lower overall mortality among people with breast cancer taking vitamin D supplements in a meta-analysis of 2 observational studies18Kanellopoulou A, Riza E, Samoli E, Benetou V. Dietary supplement use after cancer diagnosis in relation to total mortality, cancer mortality and recurrence: a systematic review and meta-analysis. Nutrition and Cancer. 2021;73(1):16-30.
- Lower markers of blood vessel formation during tamoxifen treatment among premenopausal women, but varied results for postmenopausal women, among women with breast cancer treated with 50,000 IU vitamin D weekly for 8 weeks compared to placebo in a small 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 effects19Shahvegharasl Z, Pirouzpanah S et al. Effects of cholecalciferol supplementation on serum angiogenic biomarkers in breast cancer patients treated with tamoxifen: a controlled randomized clinical trial. Nutrition. 2020;72:110656.
- No evidence of an effect on markers of tumor proliferation (Ki67) or cell death (cleaved caspase 3 apoptotic assay [CC3]) in primary breast cancer cells from newly diagnosed people treated with 40,000 IU vitamin D daily for 2 to 6 weeks before breast surgery compared to placebo in a small RCT20Arnaout A, Robertson S et al. Randomized window of opportunity trial evaluating high-dose vitamin D in breast cancer patients. Breast Cancer Research and Treatment. 2019 Nov;178(2):347-356.
Good evidence of lower mortality among people with colorectal cancer with the highest 25(OH)D levels
Insufficient (conflicting) evidencepreclinical evidence only OR clinical studies with such poor or unclear methodology that no conclusion can be drawn OR conflicting findings across clinical studies with no preponderance of evidence in one direction; conflicting evidence occurs when studies find conflicting effects (positive effect vs no effect or negative effect) with the same treatment and the same general study population (same cancer type, for example) (this is the CancerChoices definition; other researchers and studies may define this differently) of an effect on cancer progression among people with colorectal cancer with high 25(OH)D
Modest evidence of better survival, less progression, and fewer adverse cancer outcomes among people with colorectal cancer treated with vitamin D
Also see outcomes regarding advanced colorectal cancer in Advanced cancer above.
Vitamin D levels
Good evidence of lower mortality among people with colorectal cancer with the highest 25(OH)D levels
Insufficient (conflicting) evidence of an effect on cancer progression among people with colorectal cancer with high 25(OH)D
- 35% lower cancer-specific mortality among people with colorectal cancer with the highest 25(OH)D levels compared to the lowest, and a 12% lower cancer-specific mortality with each 8 ng/mL (20 nmol/L) increase of 25(OH)D concentration 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 17 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 studies21Wu G, Xue M et al. Low circulating 25-hydroxyvitamin D level is associated with increased colorectal cancer mortality: a systematic review and dose-response meta-analysis. Bioscience Reports. 2020 Jul 31;40(7):BSR20201008.
- 25% lower cancer-specific mortality among people with colorectal cancer with the highest 25(OH)D levels compared to the lowest in a meta-analysis of 7 observational studies22Vaughan-Shaw PG, O’Sullivan F et al. The impact of vitamin D pathway genetic variation and circulating 25-hydroxyvitamin D on cancer outcome: systematic review and meta-analysis. British Journal of Cancer. 2017 Apr 11;116(8):1092-1110.
- No evidence of an effect on cancer progression among people with colorectal cancer with high 25(OH)D levels compared to low levels in a meta-analysis of 2 observational studies23Vaughan-Shaw PG, O’Sullivan F et al. The impact of vitamin D pathway genetic variation and circulating 25-hydroxyvitamin D on cancer outcome: systematic review and meta-analysis. British Journal of Cancer. 2017 Apr 11;116(8):1092-1110.
- About 30% lower cancer-specific mortality among people with colorectal cancer with the highest 25(OH)D levels compared to the lowest in 2 meta-analyses of 1124Maalmi H, Walter V et al. Association between Blood 25-hydroxyvitamin D levels and survival in colorectal cancer patients: an updated systematic review and meta-analysis. Nutrients. 2018 Jul 13;10(7):896. and 525Maalmi H, Ordóñez-Mena JM, Schöttker B, Brenner H. Serum 25-hydroxyvitamin D levels and survival in colorectal and breast cancer patients: systematic review and meta-analysis of prospective cohort studies. European Journal of Cancer. 2014 May;50(8):1510-21. observational studies
- 27% lower cancer-specific mortality (5 studies), moderately better progression-free survival (2 studies), and 33% lower overall mortality (11 studies) among people with colorectal cancer with the highest 25(OH)D levels compared to the lowest in meta-analyses of observational studies26Xu J, Yuan X et al. Association of circulating 25-hydroxyvitamin D levels with colorectal cancer: an updated meta-analysis. Journal of Nutritional Science and Vitaminology (Tokyo). 2018;64(6):432-444.
- 35% lower cancer-specific mortality (3 studies) and 45% lower overall mortality (5 studies) among people with colorectal cancer with the highest levels of circulating vitamin D at diagnosis compared to the lowest in a meta-analysis of observational studies27Li M, Chen P et al. Review: the impacts of circulating 25-hydroxyvitamin D levels on cancer patient outcomes: a systematic review and meta-analysis. Journal of Clinical Endocrinology and Metabolism. 2014 Jul;99(7):2327-36.
Vitamin D supplementation and intake: modest evidence of better survival, less progression, and fewer adverse cancer outcomes among people with colorectal cancer treated with vitamin D
- Slightly better overall survival among people with colorectal cancer using vitamin D compared to no use in a meta-analysis of 4 observational studies28Xu Y, Qian M et al. The effect of vitamin D on the occurrence and development of colorectal cancer: a systematic review and meta-analysis. International Journal of Colorectal Disease. 2021 Jul;36(7):1329-1344.
- Lower levels of a tumor markera chemical or substance, such as certain proteins or genetic material, that are associated with the presence of cancer or a change in status or prognosis; these markers can be detected in blood, urine, or tissue. Tumor markers are not direct measures of clinical outcomes such as survival or metastasis, and if a therapy or treatment shows an impact only on tumor markers, we cannot surmise that it will affect survival. (carcinoembryonic antigen or CEA) during chemotherapy among people with stage 2 or 3 colorectal cancer treated with 50,000 IU vitamin D weekly for 8 weeks, whether with or without omega-3 fatty acids, compared to baseline in an uncontrolled analysisan analysis in which a therapy is used, but without a comparison group against which to judge outcomes within a small 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 effects29Haidari F, Abiri B, Iravani M, Ahmadi-Angali K, Vafa M. Effects of vitamin D and omega-3 fatty acids co-supplementation on inflammatory factors and tumor marker CEA in colorectal cancer patients undergoing chemotherapy: a randomized, double-blind, placebo-controlled clinical trial. Nutrition and Cancer. 2020;72(6):948-958.
- 33% lower cancer-specific mortality (2 RCTs), 35% less cancer progression (2 RCTs and 1 observational study), and 30% lower risk of adverse cancer outcomes (2 RCTs and 3 observational studies) among people with colorectal cancer treated with vitamin D supplements compared to placebo or a lower dose in meta-analyses30Vaughan-Shaw PG, Buijs LF et al. The effect of vitamin D supplementation on survival in patients with colorectal cancer: systematic review and meta-analysis of randomised controlled trials. British Journal of Cancer. 2020 Nov;123(11):1705-1712.
Colorectal cancer and pancreatic cancer are listed separately.
Modest evidence of higher mortality and more advanced cancer among people with stomach cancwer or liver cancer with low 25(OH)D levels
Modest evidence of lower mortality and relapse among people with stage 1–3 digestive tract cancers treated with vitamin D, especially among people with 25(OH)D levels under 40 ng/mL or with suppressed immune function
Modest evidence of substantially better 5-year relapse-free and overall survival among people with poorly differentiated adenocarcinoma taking vitamin D3 after surgery
No evidence of an effect on survival at 24 months after surgery among people with esophageal cancer taking vitamin D supplements in an 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 study
Vitamin D levels: modest evidence of higher mortality and more advanced cancer among people with stomach cancer or liver cancer with low 25(OH)D levels
- Better overall survival among people with stomach cancer (gastric carcinoma) with vitamin D levels of 20 ng/mL (50 nmol/L) or higher compared to lower levels in a mid-sized observational study31Ren C, Qiu MZ et al. Prognostic effects of 25-hydroxyvitamin D levels in gastric cancer. Journal of Translational Medicine. 2012 Jan 27;10:16.
- Higher incidence of stage 3 or 4 cancer compared to stage 1 or 2, and of lymph node metastasis compared to no metastasis before treatment among people with stomach cancer (gastric carcinoma) with lower 25(OH)D levels compared to higher levels in a mid-sized observational study32Ren C, Qiu MZ et al. Prognostic effects of 25-hydroxyvitamin D levels in gastric cancer. Journal of Translational Medicine. 2012 Jan 27;10:16.
- Higher mortality among people with liver cancer (hepatocellular carcinoma) with severe deficiency of 25(OH)D3 compared to higher levels in a mid-sized observational study33Finkelmeier F, Kronenberger B et al. Severe 25-hydroxyvitamin D deficiency identifies a poor prognosis in patients with hepatocellular carcinoma—a prospective cohort study. Alimentary Pharmacology & Therapeutics. 2014 May;39(10):1204-12.
- Higher stages of cancer or of cirrhosis among people with liver cancer (hepatocellular carcinoma) with lower levels of 25(OH)D3 compared to higher levels in a mid-sized observational study34Finkelmeier F, Kronenberger B et al. Severe 25-hydroxyvitamin D deficiency identifies a poor prognosis in patients with hepatocellular carcinoma—a prospective cohort study. Alimentary Pharmacology & Therapeutics. 2014 May;39(10):1204-12.
Vitamin D intake
Modest evidence of lower mortality and relapse among people with stage 1–3 digestive tract cancers treated with vitamin D, especially among people with 25(OH)D levels under 40 ng/mL or with suppressed immune function
Modest evidence of substantially better 5-year relapse-free and overall survival among people with poorly differentiated adenocarcinoma taking vitamin D3 after surgery
No evidence of an effect on survival at 24 months after surgery among people with esophageal cancer taking vitamin D supplements in an observational study
- Better 5-year relapse-free survival among people with stage 1–3 digestive tract cancers and with baseline serum 25(OH)D levels between 20 and 40 ng/mL treated with 2000 IU vitamin D3 daily after surgery compared to placebo, but not among people with higher baseline levels, 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 effects35Urashima M, Ohdaira H et al. Effect of vitamin D supplementation on relapse-free survival among patients with digestive tract cancers: the AMATERASU randomized clinical trial. Journal of the American Medical Association. 2019 Apr 9;321(14):1361-1369.
- Substantially lower mortality or relapse and mortality after surgery among people with stage 1–3 digestive tract cancers with the highest levels of a molecule that suppresses immune function (PD-L1), but no evidence of an effect among others, treated with 2000 IU vitamin D3 per day compared to placebo in a post-hoc analysis of a mid-sized RCT36Morita M, Okuyama M et al. Vitamin D supplementation regulates postoperative serum levels of PD-L1 in patients with digestive tract cancer and improves survivals in the highest quintile of PD-L1: a post hoc analysis of the AMATERASU randomized controlled trial. Nutrients. 2021 Jun 9;13(6):1987.
- Substantially better 5-year relapse-free and overall survival among people with poorly differentiated adenocarcinoma taking 2000 IU vitamin D3 per day after surgery compared to placebo in a post-hoc subgroup analysis of a mid-sized RCT37Yonaga H, Okada S et al. Effect modification of vitamin D supplementation by histopathological characteristics on survival of patients with digestive tract cancer: post hoc analysis of the AMATERASU randomized clinical trial. Nutrients. 2019 Oct 22;11(10):2547.
- No evidence of an effect on survival at 24 months after surgery among people with esophageal cancer taking 200–400 IU vitamin D supplements daily compared to no supplements in a mid-sized observational study38Wang L, Wang C, Wang J, Huang X, Cheng Y. Longitudinal, observational study on associations between postoperative nutritional vitamin D supplementation and clinical outcomes in esophageal cancer patients undergoing esophagectomy. Scientific Reports. 2016 Dec 13;6:38962.
No evidence of an effect on cancer progression or mortality among people with head and neck cancer with higher 25(OH)D levels in a combined analysis of 2 studies
Modest evidence of slightly better survival among people with head and neck cancer with high vitamin D intake
Vitamin D levels: no evidence of an effect on cancer progression or mortality among people with head and neck cancer with higher 25(OH)D levels in a combined analysis of 2 studies
- No evidence of an effect on cancer-specific mortality among people with head and neck cancer with the highest 25(OH)D levels 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 2 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 studies39Vaughan-Shaw PG, O’Sullivan F et al. The impact of vitamin D pathway genetic variation and circulating 25-hydroxyvitamin D on cancer outcome: systematic review and meta-analysis. British Journal of Cancer. 2017 Apr 11;116(8):1092-1110.
- No evidence of an effect on cancer progression among people with head and neck cancer with high 25(OH)D levels compared to low levels in a meta-analysis of 2 observational studies40Vaughan-Shaw PG, O’Sullivan F et al. The impact of vitamin D pathway genetic variation and circulating 25-hydroxyvitamin D on cancer outcome: systematic review and meta-analysis. British Journal of Cancer. 2017 Apr 11;116(8):1092-1110.
Vitamin D intake: modest evidence of slightly better survival among people with head and neck cancer with high vitamin D intake
- Slightly better survival over 4 to 5 years among people with head and neck cancer with high vitamin D intake compared to a regular diet, and greater benefit at 8 to 12 years, in a large meta-analysis of 16 observational studies41Pu Y, Zhu G et al. Association between vitamin D exposure and head and neck cancer: a systematic review with meta-analysis. Frontiers in Immunology. 2021 Feb 23;12:627226.
Preliminary evidence of moderately lower overall mortality but not cancer-specific mortality among people with renal cell carcinoma with higher 25(OH)D3 levels
- Moderately lower overall mortality but not cancer-specific mortality among people with renal cell carcinoma with higher concentrations of 25(OH)D3 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 study42Muller DC, Scelo G et al. Circulating 25-hydroxyvitamin D3 and survival after diagnosis with kidney cancer. Cancer Epidemiology, Biomarkers & Prevention. 2015 Aug;24(8):1277-81.
Good evidence of less cancer progression and lower mortality among people with blood cancers with higher 25(OH)D levels
- 41% lower cancer-specific mortality among people with blood cancers with high 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 16 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 studies43Vaughan-Shaw PG, O’Sullivan F et al. The impact of vitamin D pathway genetic variation and circulating 25-hydroxyvitamin D on cancer outcome: systematic review and meta-analysis. British Journal of Cancer. 2017 Apr 11;116(8):1092-1110.
- Moderately lower cancer progression among people with blood cancers with high 25(OH)D levels compared to low levels in a meta-analysis of 13 observational studies44Vaughan-Shaw PG, O’Sullivan F et al. The impact of vitamin D pathway genetic variation and circulating 25-hydroxyvitamin D on cancer outcome: systematic review and meta-analysis. British Journal of Cancer. 2017 Apr 11;116(8):1092-1110.
- 85% higher mortality and worse relapse-free survival among people with blood cancer (hematological malignancies) with low 25(OH)D levels (defined variably, but always less than 25 ng/mL) compared to normal levels (assumed higher than 25 ng/mL) in a meta-analysis of 7 observational studies45Wang W, Li G et al. Serum 25-hydroxyvitamin D levels and prognosis in hematological malignancies: a systematic review and meta-analysis. Cellular Physiology and Biochemistry. 2015;35(5):1999-2005.
- Worse event-free survival at 12 months and worse overall survival and lymphoma-specific survival at almost 5 years among people with follicular lymphoma with 25(OH)D levels less than 20 ng/mL compared to higher levels in a mid-sized observational study46Tracy SI, Maurer MJ et al. Vitamin D insufficiency is associated with an increased risk of early clinical failure in follicular lymphoma. Blood Cancer Journal. 2017 Aug 25;7(8):e595.
- 96% higher risk of relapse and subsequent 78% higher mortality among people with hematologic malignancies with 25(OH)D3 levels less than 20 ng/mL before allogeneic transplantation compared to higher levels, with higher risks among people with myeloid compared to lymphatic diseases, in a mid-sized observational study47Radujkovic A, Kordelas L et al. Pretransplant vitamin D deficiency is associated with higher relapse rates in patients allografted for myeloid malignancies. Journal of Clinical Oncology. 2017 Sep 20;35(27):3143-3152.
- Worse overall survival (18 studies) and progression-free survival (9 studies), and higher levels of advanced disease (10 studies) and a markera chemical or substance, such as certain proteins or genetic material, that are associated with the presence of cancer or a change in status or prognosis; these markers can be detected in blood, urine, or tissue. Tumor markers are not direct measures of clinical outcomes such as survival or metastasis, and if a therapy or treatment shows an impact only on tumor markers, we cannot surmise that it will affect survival. of malignancy (lactate dehydrogenase) (6 studies) among people with previously untreated lymphoma with low 25(OH)D levels, variably described across studies, compared to high levels in a meta-analysis of observational studies48Tao Y, Chen H, Zhou Y, Shi Y. Meta-analysis of the prognostic and clinical value of serum 25-hydroxyvitamin D levels in previously untreated lymphoma. Future Oncology. 2021 May;17(14):1825-1838.
- 50% lower cancer-specific mortality and 52% lower overall mortality among people with lymphoma with higher 25(OH)D levels at or near the time of diagnosis in a meta-analysis of 7 observational studies49Li M, Chen P et al. Review: the impacts of circulating 25-hydroxyvitamin D levels on cancer patient outcomes: a systematic review and meta-analysis. Journal of Clinical Endocrinology and Metabolism. 2014 Jul;99(7):2327-36.
Insufficient (conflicting) evidence of an effect on mortality among people with lung cancer with higher 25(OH)D levels, but with some evidence of variations according to genetic polymorphisms
Modest evidence of better overall and relapse-free survival among people with lung cancer taking vitamin D
Vitamin D levels: insufficient (conflicting) evidence of an effect on mortality among people with lung cancer with higher 25(OH)D levels, but with some evidence of variations according to genetic polymorphisms
- Higher cancer-specific mortality among people with lung cancer with 25(OH)D levels below about 14 ng/mL (35 nmol/L) compared to the higher levels in meta-analysesstatistical analyses that combine 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 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 studies50Feng Q, Zhang H, Dong Z, Zhou Y, Ma J. Circulating 25-hydroxyvitamin D and lung cancer risk and survival: a dose-response meta-analysis of prospective cohort studies. Medicine (Baltimore). 2017 Nov;96(45):e8613.
- No evidence of an effect on lung cancer survival overall but with variations according to genetic polymorphisms among people with lung cancer with higher 25(OH)D levels compared to lower levels in a meta-analysis of 4 observational studies51Vaughan-Shaw PG, O’Sullivan F et al. The impact of vitamin D pathway genetic variation and circulating 25-hydroxyvitamin D on cancer outcome: systematic review and meta-analysis. British Journal of Cancer. 2017 Apr 11;116(8):1092-1110.
- Worse overall survival (4 studies) and 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 worse survival (8 studies) among people with lung cancer with low circulating 25(OH)D levels compared to higher levels in meta-analyses of observational studies52Huang JD, Dong CH et al. Circulating 25-hydroxyvitamin D level and prognosis of lung cancer patients: a systematic review and meta-analysis. Bulletin du Cancer. 2017 Jul-Aug;104(7-8):675-682.
- No evidence of an effect on overall mortality among people with lung cancer with the highest 25(OH)D levels at diagnosis compared to the lowest in meta-analyses of 4 observational studies53Li M, Chen P et al. Review: the impacts of circulating 25-hydroxyvitamin D levels on cancer patient outcomes: a systematic review and meta-analysis. Journal of Clinical Endocrinology and Metabolism. 2014 Jul;99(7):2327-36.
Vitamin D intake
Modest evidence of better overall and relapse-free survival among people with lung cancer taking vitamin D
Preliminary evidence of better 5-year relapse-free survival and overall survival among people with both early stage lung adenocarcinoma and low 25(OH)D levels treated with vitamin D
- Better overall and relapse-free survival among people with lung cancer taking vitamin D compared to non-users in a meta-analysis of 10 observational studies54Qian M, Lin J et al. The role of vitamin D intake on the prognosis and incidence of lung cancer: a systematic review and meta-analysis. Journal of Nutritional Science and Vitaminology (Tokyo). 2021;67(5):273-282.
- Better 5-year relapse-free survival and overall survival among people with both early stage lung adenocarcinoma and low 25(OH)D levels, but no evidence of an effect on survival among the full group of people with resected non-small cell lung cancer treated with 1200 IU/day vitamin D compared to placebo 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 effects55Akiba T, Morikawa T et al. Vitamin D supplementation and survival of patients with non-small cell lung cancer: a randomized, double-blind, placebo-controlled trial. Clinical Cancer Research. 2018 Sep 1;24(17):4089-4097.
Modest evidence of higher overall mortality among people with skin cancer with low 25(OH)D levels
Weak evidence of higher cancer-specific mortality among people with skin cancer with low 25(OH)D levels
Preliminary and conflicting evidence of lower progression among people with melanoma with higher 25(OH)D levels in a combined analysis of studies
Preliminary evidence of lower risk of relapse among people with melanoma with tumor thickness 0.75 mm or more with increases in 25(OH)D levels
Preliminary evidence of lower risk of advanced tumors at diagnosis among people with melanoma with higher 25(OH)D3 levels
Also see outcomes regarding advanced melanoma in Advanced cancer above.
Vitamin D levels
Modest evidence of higher overall mortality among people with skin cancer with low 25(OH)D levels
- 56% higher mortality among people with melanoma with vitamin D deficiency (undefined) compared to sufficiency 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 25 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 studies56Tsai TY, Kuo CY, Huang YC. The association between serum vitamin D level and risk and prognosis of melanoma: a systematic review and meta-analysis. Journal of the European Academy of Dermatology and Venereology. 2020 Aug;34(8):1722-1729.
Weak evidence of higher cancer-specific mortality among people with skin cancer with low 25(OH)D levels
- 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 lower cancer-specific mortality among people with skin cancer with 25(OH)D levels higher than about 20 ng/L compared to lower levels in a meta-analysis of 2 observational studies57Vaughan-Shaw PG, O’Sullivan F et al. The impact of vitamin D pathway genetic variation and circulating 25-hydroxyvitamin D on cancer outcome: systematic review and meta-analysis. British Journal of Cancer. 2017 Apr 11;116(8):1092-1110.
Preliminary and conflicting evidence of lower progression among people with melanoma with higher 25(OH)D levels in a combined analysis of studies
- Moderately lower cancer progression among people with skin cancer with higher 25(OH)D levels compared to lower levels in a meta-analysis of 2 observational studies58Vaughan-Shaw PG, O’Sullivan F et al. The impact of vitamin D pathway genetic variation and circulating 25-hydroxyvitamin D on cancer outcome: systematic review and meta-analysis. British Journal of Cancer. 2017 Apr 11;116(8):1092-1110.
- No evidence of an effect on Breslow thickness, tumor ulceration, or disease stage a year or more after diagnosis among people with resected stage 2B–3C melanoma with higher 25(OH)D levels compared to lower levels in a mid-sized observational study59Lipplaa A, Fernandes R et al. 25-hydroxyvitamin D serum levels in patients with high risk resected melanoma treated in an adjuvant bevacizumab trial. British Journal of Cancer. 2018 Oct;119(7):793-800.
Preliminary evidence of lower risk of relapse among people with melanoma with tumor thickness 0.75 mm or more with increases in 25(OH)D levels
- Lower risk of relapse among people with melanoma with tumor thickness 0.75 mm or more with each 8 ng/mL (20 nmol/L) increase in 25(OH)D levels, with stronger effects January to March than in other months, in a mid-sized observational study60Newton-Bishop JA, Beswick S et al. Serum 25-hydroxyvitamin D3 levels are associated with Breslow thickness at presentation and survival from melanoma. Journal of Clinical Oncology. 2009 Nov 10;27(32):5439-44.
Preliminary evidence of lower risk of advanced tumors at diagnosis among people with melanoma with higher 25(OH)D3 levels
- Lower risk of advanced tumors (smaller Breslow thickness) at diagnosis among people with melanoma with higher 25(OH)D3 levels compared to lower levels in a mid-sized observational study61Newton-Bishop JA, Beswick S et al. Serum 25-hydroxyvitamin D3 levels are associated with Breslow thickness at presentation and survival from melanoma. Journal of Clinical Oncology. 2009 Nov 10;27(32):5439-44.
Vitamin D intake: weak evidence of lower risk of relapse and better overall survival among people with melanoma taking vitamin D supplements
- Weak trends toward lower risk of relapse and better overall survival among people with melanoma taking vitamin D supplements compared to no supplements in a mid-sized observational study62Newton-Bishop JA, Beswick S et al. Serum 25-hydroxyvitamin D3 levels are associated with Breslow thickness at presentation and survival from melanoma. Journal of Clinical Oncology. 2009 Nov 10;27(32):5439-44.
Modest evidence of slightly longer survival among people with ovarian cancer with higher 25(OH)D levels at diagnosis, but no evidence of an effect on progression-free survival after treatment
- Slightly longer survival among people with ovarian cancer with higher 25(OH)D levels at diagnosis, but no evidence of an effect on progression-free survival from higher levels after primary treatment 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 study63Webb PM, de Fazio A et al; Australian Ovarian Cancer Study Group. Circulating 25-hydroxyvitamin D and survival in women with ovarian cancer. American Journal of Clinical Nutrition. 2015 Jul;102(1):109-14.
Modest evidence of lower mortality among people with pancreatic cancer with higher 25(OH)D levels
Also see outcomes regarding advanced ovarian cancer in Advanced cancer above.
- 19% lower mortality among people with pancreatic cancer with higher 25(OH)D levels compared to lower 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 5 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 studies64Zhang X, Huang XZ et al. Plasma 25-hydroxyvitamin D levels, vitamin D intake, and pancreatic cancer risk or mortality: a meta-analysis. Oncotarget. 2017 Jun 29;8(38):64395-64406.
Modest evidence of lower mortality among people with prostate cancer with higher vitamin D levels
Weak evidence of less progression (better PSA response proportionthe percentage of people who achieved a defined reduction in PSA, typically set at 50% reduction or more indicating a reduction in serum PSA levels, or positive coresbiopsy samples testing positive for cancer ) among people with prostate cancer treated with vitamin D supplements
Also see outcomes regarding advanced prostate cancer in Advanced cancer above.
Vitamin D levels: modest evidence of lower mortality among people with prostate cancer with higher vitamin D levels
- 9% lower all-cause mortality and prostate cancer-specific mortality with each 8 ng/mL (20 nmol/L) increase in circulating vitamin D levels among people with prostate cancer 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 7 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 studies65Song ZY, Yao Q, Zhuo Z, Ma Z, Chen G. Circulating vitamin D level and mortality in prostate cancer patients: a dose-response meta-analysis. Endocrine Connections. 2018 Dec 1;7(12):R294-R303.
- 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 lower cancer-specific mortality among people with prostate cancer with higher vitamin D levels compared to low levels (generally below 20 ng/mL) in a meta-analysis of 4 observational studies66Vaughan-Shaw PG, O’Sullivan F et al. The impact of vitamin D pathway genetic variation and circulating 25-hydroxyvitamin D on cancer outcome: systematic review and meta-analysis. British Journal of Cancer. 2017 Apr 11;116(8):1092-1110.
Vitamin D intake
Weak evidence of less progression (better PSA response proportion indicating a reduction in serum PSA levels, or positive cores) among people with prostate cancer treated with vitamin D supplements
- No evidence of an effect on mortality or PSA change from baseline, but a weak trend toward higher PSA response proportion among people with prostate cancer treated with vitamin D supplements compared to controls in a meta-analysis of 6 RCTsrandomized 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 effects67Shahvazi S, Soltani S, Ahmadi SM, de Souza RJ, Salehi-Abargouei A. The effect of vitamin D supplementation on prostate cancer: a systematic review and meta-analysis of clinical trials. Hormone and Metabolic Research. 2019 Jan;51(1):11-21.
- 19% better PSA response proportion among people with prostate cancer taking oral vitamin D, either with or without chemotherapy treatment, in a meta-analysis of 16 uncontrolled trialsa study in which a therapy is used, but without a comparison group against which to judge outcomes; an uncontrolled trial is considered a weak study design68Shahvazi S, Soltani S, Ahmadi SM, de Souza RJ, Salehi-Abargouei A. The effect of vitamin d supplementation on prostate cancer: a systematic review and meta-analysis of clinical trials. Hormone and Metabolic Research. 2019 Jan;51(1):11-21.
- Fewer positive cores at repeat biopsy among people with early stage, low-risk prostate cancer under active surveillance treated with 4000 IU vitamin D daily for 1 year compared to baseline in a small uncontrolled trial69Hollis BW, Marshall DT et al. Vitamin D3 supplementation, low-risk prostate cancer, and health disparities. Journal of Steroid Biochemistry and Molecular Biology. 2013 Jul;136:233-7.
Weak evidence of less tumor progression among people with colorectal adenoma treated with vitamin D and calcium
No evidence of an effect on mortality among people with blood cancer (hematologic malignancy) treated with calcium and vitamin D supplements
Preliminary evidence of better overall survival among people with acute myeloid leukemia and NPM1 mutations but no evidence of an effect among people with wild-type NPM1 treated with supplemental vitamin C and vitamin D
Weak evidence of complete remission in a single person with high grade, non-muscle involved bladder cancer refractory to Bacillus Calmette-Guerin treated with intravenous pharmacological ascorbate and subcutaneous mistletoe along with several supplements
Weak evidence of lower prostate specific antigen (PSA) among some men with biochemically recurrent prostate cancer with rising PSA treated with Prostate Health Cocktail (PHC)
Vitamin D and calcium
Weak evidence of less tumor progression among people with colorectal adenoma treated with vitamin D and calcium
No evidence of an effect on mortality among people with blood cancer (hematologic malignancy) treated with calcium and vitamin D supplements
- 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 or marginally significant biomarkera chemical or substance, such as certain proteins or genetic material, that are associated with the presence of cancer or a change in status or prognosis; these markers can be detected in blood, urine, or tissue. Tumor markers are not direct measures of clinical outcomes such as survival or metastasis, and if a therapy or treatment shows an impact only on tumor markers, we cannot surmise that it will affect survival. changes toward less tumor progression 1 year after biopsy among people with colorectal adenoma treated with 1,000 IU vitamin D and 1,200 mg calcium per day, but not either supplement alone, compared to placebo in a mid-sized study sample of participants from a 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 effects70Gao Y, Um CY et al. Effects of supplemental vitamin D and calcium on markers of proliferation, differentiation, and apoptosis in the normal colorectal mucosa of colorectal adenoma patients. Public Library of Science One. 2018 Dec 17;13(12):e0208762.
- No evidence of an effect on mortality among people with hematologic malignancy treated with calcium and vitamin D supplements compared to no supplements in a very large RCT71Ammann EM, Drake MT et al. Incidence of hematologic malignancy and cause-specific mortality in the Women’s Health Initiative randomized controlled trial of calcium and vitamin D supplementation. Cancer. 2017 Nov 1;123(21):4168-4177.
Vitamin D supplements and vitamin C: preliminary evidence of better overall survival among people with acute myeloid leukemia and NPM1 mutations but no evidence of an effect among people with wild-type NPM1 treated with supplemental vitamin C and vitamin D
- Better overall survival among people with acute myeloid leukemia and NPM1 mutations but no evidence of an effect among people with wild-type NPM1, and no evidence of any effect on response rate, or relapse incidence among those treated with supplemental vitamin C and vitamin D from day 10 of chemotherapy until hematologic recovery from induction and consolidation compared to no supplementation 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 study72Mouchel PL, Bérard E et al. Vitamin C and D supplementation in acute myeloid leukemia. Blood Advances. 2023 Sep 6:bloodadvances.2023010559.
Vitamin D supplements with mistletoe, pharmacological ascorbate, probiotics, and several other supplements: weak evidence of complete remission in a single person with high grade, non-muscle involved bladder cancer refractory to Bacillus Calmette-Guerin treated with intravenous pharmacological ascorbate and subcutaneous mistletoe along with several supplements
- Complete remission (no evidence of disease) in a nonsmoking woman with high grade, non-muscle involved bladder cancer (carcinoma in situ) refractory to Bacillus Calmette-Guerin treated with intravenous pharmacological ascorbate and subcutaneous mistletoe 3 times a week, and also intravenous and intravesical mistletoe once a week for an 8-week induction treatment using a dose-escalation protocol and then maintenance therapy of the same protocol for 3 weeks every 3 months for 2 years; plus the supplements below in a case studya descriptive and exploratory analysis of a person, group, or event regarding changes observed over time; because changes due to treatment are not compared to similar changes over time without treatment, a case study is considered a weak study design:73Davis D, Seely D et al. Complete remission of BCG-refractory high-grade bladder CIS with pharmacologic ascorbate and mistletoe. Alternative Therapies in Health and Medicine. 2023 May;29(4):6-17.
- Daily: turmeric, vitamin D, omega-3 fatty acids, coenzyme Q10, chaga mushroom, and melatonin at night
- During induction: probiotics
- During maintenance: probiotics, melatonin 4 times a day, and a fiber supplement made of flaxseed, probiotics, and L-glutamine
Prostate Health Cocktail (PHC), a combination of vitamin D3 (cholecalciferol), vitamin E (alpha tocopherol), selenium (L-selenomethionine), green tea extract (epigallocatechin), saw palmetto berry (permixon), soy isoflavones (genistein and daidzein), and lycopene: weak evidence of lower prostate specific antigen (PSA) among some men with biochemically recurrent prostate cancer with rising PSA treated with PHC
- Lower PSA at 12 weeks among 22.5% of men but rising PSA among 77.8% of men with biochemically recurrent prostate cancer with rising PSA but no radiographic metastases treated with 3 capsules of PHC a day for 4 weeks compared to baseline in a small uncontrolled triala study in which a therapy is used, but without a comparison group against which to judge outcomes; an uncontrolled trial is considered a weak study design74Dorff TB, Groshen S et al. A phase II trial of a combination herbal supplement for men with biochemically recurrent prostate cancer. Prostate Cancer and Prostatic Diseases. 2014 Dec;17(4):359-65.
Optimizing your body terrain
Does vitamin D promote an environment within your body that is less supportive of cancer development, growth, or spread? We present the evidence.
See Optimizing Your Body Terrain ›
Find medical professionals who specialize in managing body terrain factors: Finding Integrative Oncologists and Other Practitioners ›
We also recommend that you share with your doctor the information here about how vitamin D might affect these terrain factors if you have any imbalances.
Good evidence of a link between overweight or larger waist circumference and lower 25(OH)D levels
Modest evidence of a link between metabolic health and 25(OH)D levels among people with obesity
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. on body weight among postmenopausal women treated with vitamin D in a small study
Vitamin D levels: good evidence of a link between overweight or larger waist circumference and lower 25(OH)D levels
- Smaller waist circumference among people with 25(OH)D levels 30 ng/mL (75 nmol/L) or higher compared to levels less than 12 ng/mL (30 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 study75Ganji V, Tangpricha V, Zhang X. Serum vitamin D concentration ≥75 nmol/L is related to decreased cardiometabolic and inflammatory biomarkers, metabolic syndrome, and diabetes; and increased cardiorespiratory fitness in US adults. Nutrients. 2020 Mar 10;12(3):730.
- A higher level of obesity and truncal fat mass among people with obesity with the lowest 25(OH)D levels compared to the highest in a mid-sized observational study76Bellia A, Garcovich C et al. Serum 25-hydroxyvitamin D levels are inversely associated with systemic inflammation in severe obese subjects. Internal and Emergency Medicine. 2013 Feb;8(1):33-40.
- Higher 25(OH)D levels among people with metabolically healthy obesity compared to metabolically unhealthy obesity in a large observational study77Esteghamati A, Aryan Z, Esteghamati A, Nakhjavani M. Differences in vitamin D concentration between metabolically healthy and unhealthy obese adults: associations with inflammatory and cardiometabolic markers in 4391 subjects. Diabetes & Metabolism. 2014 Nov;40(5):347-55.
- Higher risk of low vitamin D levels among people with high body mass index compared to other people in a meta-analysis of 4 observational studies78Xu J, Yuan X et al. Association of circulating 25-hydroxyvitamin D levels with colorectal cancer: an updated meta-analysis. Journal of Nutritional Science and Vitaminology (Tokyo). 2018;64(6):432-444.
Vitamin D intake: no evidence of an effect on body weight among postmenopausal women treated with vitamin D in a small study
- No evidence of an effect on body weight among postmenopausal women treated with 2000 IU vitamin D3 daily, 0.25 micrograms l alpha OHD3 daily for 2 years, or 0.25-0.50 micrograms 1,25 (OH)2D3 daily for 1 year compared to placebo 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 effects79Nilas L, Christiansen C. Treatment with vitamin D or its analogues does not change body weight or blood glucose level in postmenopausal women. International Journal of Obesity. 1984;8(5):407-11.
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 higher insulin sensitivity and better blood glucose levels among people at risk for type 2 diabetes with higher 25(OH)D levels
Preliminary evidence of lower 25(OH)D levels among people with diabetes
Weak (conflicting) 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 an effect on glycemic control (HbA1c), fasting blood glucose, insulin levels, and other measures of blood glucose and insulin balance among people with diabetes or insulin resistance
Preliminary evidence of lower insulin resistance and better insulin sensitivity among people with diabetes or insulin resistance treated with vitamin D3
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 type 2 diabetes among people with lower 25(OH)D levels
Good evidence of better markers of glycemic control and lower risk of insulin resistance among people without diabetes with higher 25(OH)D levels
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 lower fasting glucose among women with polycystic ovary syndrome treated with vitamin D
Weak evidence of lower insulin levels among women with polycystic ovary syndrome taking vitamin D supplements, but only when used in combination with calcium, vitamin K, zinc, or magnesium
Modest evidence of lower insulin resistance and higher insulin sensitivity among people treated with vitamin D
Modest evidence of a slightly lower risk of type 2 diabetes among women with the highest vitamin D intake from supplements
Among people with diabetes or at high risk of diabetes
Vitamin D levels
Preliminary evidence of higher insulin sensitivity and better glycemic control (HbA1c) among people at risk for type 2 diabetes with higher 25(OH)D levels
- Higher insulin sensitivity and lower HOMA-IR among people at risk for type 2 diabetes with higher 25(OH)D levels compared to lower 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 study80Kayaniyil S, Vieth R et al. Association of vitamin D with insulin resistance and beta-cell dysfunction in subjects at risk for type 2 diabetes. Diabetes Care. 2010 Jun;33(6):1379-81,
- A higher risk of more insulin resistance and higher levels of fasting and post-challenge glucose among people with obesity with the lowest 25(OH)D levels compared to the highest in a mid-sized observational study81Bellia A, Garcovich C et al. Serum 25-hydroxyvitamin D levels are inversely associated with systemic inflammation in severe obese subjects. Internal and Emergency Medicine. 2013 Feb;8(1):33-40.
Preliminary evidence of lower 25(OH)D levels among people with diabetes
- Lower 25(OH)D3 levels among people with diabetes compared to controls, and a weak trend toward lower HbA1c among people with diabetes with higher 25(OH)D3 levels in a mid-sized observational study82Kostoglou-Athanassiou I, Athanassiou P, Gkountouvas A, Kaldrymides P. Vitamin D and glycemic control in diabetes mellitus type 2. Therapeutic Advances in Endocrinology and Metabolism. 2013 Aug;4(4):122-8.
Vitamin D intake
Weak (conflicting) evidence of an effect on glycemic control (HbA1c), fasting blood glucose, insulin levels, and other measures of blood glucose and insulin balance among people with diabetes or insulin resistance treated with vitamin D3
- 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. on HbA1c among people with type 2 diabetes mellitus with stable glycemic control and with vitamin D levels less than 20 ng/mL treated with 1000 IU daily of cholecalciferol combined with 100 mg of elemental calcium twice a day for 24 weeks compared to calcium alone 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 effects83Ryu OH, Lee S et al. A prospective randomized controlled trial of the effects of vitamin D supplementation on long-term glycemic control in type 2 diabetes mellitus of Korea. Endocrine Journal. 2014;61(2):167-76.
- Lower HbA1c, but no other change in glucose indices (FBS, insulin, and IR) among people with type 2 diabetes treated with 50,000 IU vitamin D per week for 8 weeks compared to placebo in a small RCT84Safarpour P, Daneshi-Maskooni M et al. Vitamin D supplementation improves SIRT1, Irisin, and glucose indices in overweight or obese type 2 diabetic patients: a double-blind randomized placebo-controlled clinical trial. BMC Family Practice. 2020 Feb 7;21(1):26.
- No evidence of an effect on fasting glucose, insulin, or HbA1c levels among people with type 2 diabetes but without vitamin D deficiency treated with 40,000 IU cholecalciferol per week for 6 months compared to placebo in a small RCT85Jorde R, Figenschau Y. Supplementation with cholecalciferol does not improve glycaemic control in diabetic subjects with normal serum 25-hydroxyvitamin D levels. European Journal of Nutrition. 2009 Sep;48(6):349-54.
- No evidence of an effect on glucose homeostasis parameters among people with type 2 diabetes treated with 1000 units vitamin D per day for 12 months compared to placebo in a small RCT86Breslavsky A, Frand J et al. Effect of high doses of vitamin D on arterial properties, adiponectin, leptin and glucose homeostasis in type 2 diabetic patients. Clinical Nutrition. 2013 Dec;32(6):970-5.
Preliminary evidence of lower insulin resistance and better insulin sensitivity among people with diabetes or insulin resistance treated with vitamin D3
- Lower insulin resistance (HOMA-IR) levels among people with diabetes drinking a yogurt drink fortified with 500 IU vitamin D3 twice a day for 12 weeks compared to an unfortified drink in a small RCT87Neyestani TR, Nikooyeh B et al. Improvement of vitamin D status via daily intake of fortified yogurt drink either with or without extra calcium ameliorates systemic inflammatory biomarkers, including adipokines, in the subjects with type 2 diabetes. Journal of Clinical Endocrinology and Metabolism. 2012 Jun;97(6):2005-11.
- Better insulin sensitivity and insulin resistance and lower fasting insulin among insulin-resistant women with 25(OH)D levels less than 20 ng/mL (50 nmol/L) treated with 4000 IU vitamin D3 per day for 6 months compared to placebo in a small RCT88von Hurst PR, Stonehouse W, Coad J. Vitamin D supplementation reduces insulin resistance in South Asian women living in New Zealand who are insulin resistant and vitamin D deficient—a randomised, placebo-controlled trial. British Journal of Nutrition. 2010 Feb;103(4):549-55.
Among people without diabetes
Vitamin D levels
Good evidence of higher risk of type 2 diabetes among people with lower 25(OH)D levels
Good evidence of better markers of glycemic control and lower risk of insulin resistance among people without diabetes with higher 25(OH)D levels
- 38% lower risk of type 2 diabetes among people with the highest 25(OH)D levels compared to the lowest, and a 4% lower risk of type 2 diabetes with each increase of 4 ng/mL (10 nmol/L) 25(OH)D 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 observational studies89Song Y, Wang L et al. Blood 25-hydroxy vitamin D levels and incident type 2 diabetes: a meta-analysis of prospective studies. Diabetes Care. 2013 May;36(5):1422-8.
- Moderately lower prevalence of type 2 diabetes among non-blacks with the highest 25(OH)D levels compared to the lowest in a meta-analysis of 4 observational studies90Pittas AG, Lau J, Hu FB, Dawson-Hughes B. The role of vitamin D and calcium in type 2 diabetes. A systematic review and meta-analysis. Journal of Clinical Endocrinology and Metabolism. 2007 Jun;92(6):2017-29.
- Lower 25(OH)D levels at baseline among people who developed type 2 diabetes during 5 years compared to people who didn’t develop diabetes, with a 24% reduced risk of diabetes with each 10 ng/mL (25 nmol/L) increase in serum 25OHD in a large observational study91Gagnon C, Lu ZX et al. Serum 25-hydroxyvitamin D, calcium intake, and risk of type 2 diabetes after 5 years: results from a national, population-based prospective study (the Australian Diabetes, Obesity and Lifestyle study). Diabetes Care. 2011 May;34(5):1133-8.
Good evidence of better markers of glycemic control and lower risk of insulin resistance among people without diabetes with higher 25(OH)D levels
- Substantially higher risk of insulin resistance and glycated hemoglobin (HbA1c) among people with less than 12 ng/mL (30 nmol/L) vitamin D compared to 30 ng/mL (75 nmol/L) or higher in a very large observational study92Ganji V, Tangpricha V, Zhang X. Serum vitamin D concentration ≥75 nmol/L is related to decreased cardiometabolic and inflammatory biomarkers, metabolic syndrome, and diabetes; and increased cardiorespiratory fitness in US adults. Nutrients. 2020 Mar 10;12(3):730.
- Lower HbA1c levels among people with rising 25(OH)D3 levels in a mid-sized observational study93Kostoglou-Athanassiou I, Athanassiou P, Gkountouvas A, Kaldrymides P. Vitamin D and glycemic control in diabetes mellitus type 2. Therapeutic Advances in Endocrinology and Metabolism. 2013 Aug;4(4):122-8.
- Lower HbA1c and higher basal and oral glucose tolerance test (OGTT)-stimulated insulin levels with rising 25(OH)D3 levels among people with obesity in a mid-sized observational study94Bellan M, Guzzaloni G et al. Altered glucose metabolism rather than naive type 2 diabetes mellitus (T2DM) is related to vitamin D status in severe obesity. Cardiovascular Diabetology. 2014 Mar 11;13:57.
- Lower fasting plasma glucose and HbA1c among people with metabolically healthy obesity with higher 25(OH)D compared to lower levels, but no evidence of an effect among people with metabolically unhealthy obesity in a large observational study95Esteghamati A, Aryan Z, Esteghamati A, Nakhjavani M. Differences in vitamin D concentration between metabolically healthy and unhealthy obese adults: associations with inflammatory and cardiometabolic markers in 4391 subjects. Diabetes & Metabolism. 2014 Nov;40(5):347-55.
Vitamin D intake
Modest evidence of lower fasting glucose among women with polycystic ovary syndrome treated with vitamin D
- Lower fasting glucose concentration, with stronger effects at higher doses, but no evidence of an effect on fasting insulin concentration or HOMA-IR among women with polycystic ovary syndrome treated with vitamin D in a meta-analysis of 10 RCTs96Wang L, Wen X et al. Effects of vitamin D supplementation on metabolic parameters of women with polycystic ovary syndrome: a meta-analysis of randomized controlled trials. Gynecological Endocrinology. 2021 May;37(5):446-455.
Weak evidence of lower insulin levels among women with polycystic ovary syndrome taking vitamin D supplements, but only when used in combination with calcium, vitamin K, zinc, or magnesium
- A weak trend toward lower glucose concentrations among women with polycystic ovary syndrome taking vitamin D supplements, with stronger effects when used in combination with calcium, vitamin K, zinc, or magnesium (3 studies) compared to vitamin D alone (7 studies) in a meta-analysis of 10 RCTs97Łagowska K, Bajerska J, Jamka M. The role of vitamin D oral supplementation in insulin resistance in women with polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled trials. Nutrients. 2018 Nov 2;10(11):1637.
Modest evidence of lower insulin resistance and higher insulin sensitivity among people treated with vitamin D
- No evidence of an effect on insulin concentrations among women with polycystic ovary syndrome taking vitamin D supplements, although a weak trend toward lower insulin when used in combination with calcium, vitamin K, zinc, or magnesium (3 studies) compared to vitamin D alone (7 studies) in a meta-analysis of 10 RCTs98Łagowska K, Bajerska J, Jamka M. The role of vitamin D oral supplementation in insulin resistance in women with polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled trials. Nutrients. 2018 Nov 2;10(11):1637.
- Lower HOMA-IR indices among women with polycystic ovary syndrome taking less than 4000 IU vitamin D per day but not with higher doses or weekly dosing, and stronger effects when used in combination with calcium, vitamin K, zinc, or magnesium (3 studies) compared to vitamin D alone (7 studies) in a meta-analysis of 10 RCTs99Łagowska K, Bajerska J, Jamka M. The role of vitamin D oral supplementation in insulin resistance in women with polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled trials. Nutrients. 2018 Nov 2;10(11):1637.
- Lower HOMA-IR but no evidence of an effect on fasting glucose or fasting insulin among women with polycystic ovarian syndrome treated with vitamin D compared to placebo in a meta-analysis of 9 RCTs100Pergialiotis V, Karampetsou N, Panagopoulos P, Trakakis E, Papantoniou N. The effect of Vitamin D supplementation on hormonal and glycaemic profile of patients with PCOS: a meta-analysis of randomised trials. International Journal of Clinical Practice. 2017 Jun;71(6).
- Comparable effects on fasting blood glucose or HOMA-IR among older adults treated with either 800 or 2000 IU vitamin D3 per day for 2 years in a mid-sized RCT101Grübler MR, Gängler S, Egli A, Bischoff-Ferrari HA. Effects of vitamin D3 on glucose metabolism in patients with severe osteoarthritis: a randomized double-blind trial comparing daily 2000 with 800 IU vitamin D3. Diabetes, Obesity and Metabolism. 2021 Apr;23(4):1011-1019.
- Lower fasting blood glucose and higher insulin sensitivity among women with grade 2 or 3 cervical intraepithelial neoplasia treated with 50,000 IU vitamin D3 every 2 weeks for 6 months compared to placebo in a small RCT102Vahedpoor Z, Mahmoodi S et al. Long-term vitamin D supplementation and the effects on recurrence and metabolic status of cervical intraepithelial neoplasia grade 2 or 3: a randomized, double-blind, placebo-controlled trial. Annals of Nutrition and Metabolism. 2018;72(2):151-160.
- No evidence of an effect on blood glucose levels among postmenopausal women treated with 2000 IU vitamin D3 daily, or 0.25 micrograms l alpha OHD3 daily for 2 years, or 0.25-0.50 micrograms 1,25(OH)2D3 daily for 1 year, compared to placebo in a mid-sized RCT103Nilas L, Christiansen C. Treatment with vitamin D or its analogues does not change body weight or blood glucose level in postmenopausal women. International Journal of Obesity. 1984;8(5):407-11.
Modest evidence of a slightly lower risk of type 2 diabetes among women with the highest vitamin D intake from supplements
- Slightly lower risk of type 2 diabetes during 20 years of follow-up among women with no history of diabetes, cardiovascular disease, or cancer at baseline with the highest vitamin D intake from supplements compared with the lowest, but no evidence of an effect with overall vitamin D intake in a very large observational study104Pittas AG, Dawson-Hughes B et al. Vitamin D and calcium intake in relation to type 2 diabetes in women. Diabetes Care. 2006 Mar;29(3):650-6.
Changes in hormone levels seen in the studies here may not be beneficial in every situation. Your oncology team needs to determine whether any changes would be favorable for your condition.
Preliminary evidence of higher incidence of early onset of menstruation (menarche) among girls with low 25(OH)D levels
Preliminary (conflicting) evidence of better balance of some sex hormones among people with imbalances treated with vitamin D
Insufficient evidencepreclinical evidence only OR clinical studies with such poor or unclear methodology that no conclusion can be drawn OR conflicting findings across clinical studies with no preponderance of evidence in one direction; conflicting evidence occurs when studies find conflicting effects (positive effect vs no effect or negative effect) with the same treatment and the same general study population (same cancer type, for example) (this is the CancerChoices definition; other researchers and studies may define this differently) of an effect on parathyroid hormone among people with low 25(OH)D levels treated with vitamin D
Preliminary evidence of a substantial increase in leptin, which inhibits hunger responses, among people with type 2 diabetes treated with vitamin D
Sex hormones
Vitamin D levels: preliminary evidence of higher incidence of early onset of menstruation (menarche) among girls with low 25(OH)D levels
- Earlier menarche among girls with 25(OH)D levels below 20 ng/mL (50 nmol/L) compared to 30 ng/mL (75 nmol/L) or higher 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 study105Villamor E, Marin C, Mora-Plazas M, Baylin A. Vitamin D deficiency and age at menarche: a prospective study. American Journal of Clinical Nutrition. 2011 Oct;94(4):1020-5.
Vitamin D intake: preliminary (conflicting) evidence of better balance of some sex hormones among people with imbalances treated with vitamin D
- Lower dehydroepiandrosterone sulfate (DHEAS) but no evidence of an effect on serum testosterone or luteinizing hormone (LH) among women with polycystic ovarian syndrome treated with vitamin D compared to placebo 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 9 RCTsrandomized 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 effects;106Pergialiotis V, Karampetsou N, Panagopoulos P, Trakakis E, Papantoniou N. The effect of Vitamin D supplementation on hormonal and glycaemic profile of patients with PCOS: a meta-analysis of randomised trials. International Journal of Clinical Practice. 2017 Jun;71(6). high blood levels of dehydroepiandrosterone have been associated with increased risk of breast, ovarian cancers, and DHEA supplementation also resulted in flare-up of prostate cancer107Dehydroepiandrosterone. Memorial Sloan Kettering Cancer Center. March 5, 2020. Viewed July 12, 2022.
- Better serum total testosterone but no evidence of an effect on free testosterone, dehydroepiandrosterone sulfate (DHEA-S), sex hormone-binding globulin (SHBG), or free androgen index (FAI) among people with polycystic ovary syndrome treated with vitamin D compared to controls in a meta-analysis of 18 RCTs108Zhao JF, Li BX, Zhang Q. Vitamin D improves levels of hormonal, oxidative stress and inflammatory parameters in polycystic ovary syndrome: a meta-analysis study. Annals of Palliative Medicine. 2021 Jan;10(1):169-183.
- Lower levels of total testosterone and free androgen index, and higher levels of sex hormone binding globulin among overweight females aged 18–49 years with vitamin D deficiency and polycystic ovary syndrome treated with 50,000 IU vitamin D3 per week for 12 weeks compared to placebo in a small RCT;109Al-Bayyari N, Al-Domi H, Zayed F, Hailat R, Eaton A. Androgens and hirsutism score of overweight women with polycystic ovary syndrome improved after vitamin D treatment: a randomized placebo controlled clinical trial. Clinical Nutrition. 2021 Mar;40(3):870-878. higher levels of sex hormone binding globulin is associated with decreased risk of breast cancer in postmenopausal women110He XY, Liao YD, Yu S, Zhang Y, Wang R. Sex hormone binding globulin and risk of breast cancer in postmenopausal women: a meta-analysis of prospective studies. Hormone and Metabolic Research. 2015 Jun;47(7):485-90.
Other hormones
Insufficient evidence of an effect on parathyroid hormone (PTH) among people with low 25(OH)D levels treated with vitamin D; PTH manages blood calcium levels and may possibly promote some types of cancer111McCarty MF. Parathyroid hormone may be a cancer promoter—an explanation for the decrease in cancer risk associated with ultraviolet light, calcium, and vitamin D. Medical Hypotheses. 2000 Mar;54(3):475-82.
- 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. on levels of parathyroid hormone among people with type 2 diabetes with stable glycemic control and with vitamin D levels less than 20 ng/mL treated with 1000 IU daily of cholecalciferol combined with 100 mg of elemental calcium twice a day for 24 weeks compared to calcium alone in a mid-sized RCT112Ryu OH, Lee S et al. A prospective randomized controlled trial of the effects of vitamin D supplementation on long-term glycemic control in type 2 diabetes mellitus of Korea. Endocrine Journal. 2014;61(2):167-76.
- Lower levels of parathyroid hormone among overweight females aged 18–49 years with vitamin D deficiency and polycystic ovary syndrome treated with 50,000 IU vitamin D3 per week for 12 weeks compared to placebo in a small RCT113Al-Bayyari N, Al-Domi H, Zayed F, Hailat R, Eaton A. Androgens and hirsutism score of overweight women with polycystic ovary syndrome improved after vitamin D treatment: a randomized placebo controlled clinical trial. Clinical Nutrition. 2021 Mar;40(3):870-878.
- 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 parathyroid hormone (PTH) at 12 months and significantly lower PTH at 24 months among premenopausal women at high risk breast of cancer with a baseline 25(OH)D level of 32 ng/mL or lower treated with 20,000 IU vitamin D per week for a year compared to placebo in a mid-sized RCT114Crew KD, Anderson GL et al. Randomized double-blind placebo-controlled biomarker modulation study of vitamin D supplementation in premenopausal women at high risk for breast cancer (SWOG S0812). Cancer Prevention Research (Philadelphia). 2019 Jul;12(7):481-490.
Preliminary evidence of a substantial increase in leptin, which inhibits hunger responses, among people with type 2 diabetes treated with vitamin D
- A substantial increase in leptin among people with type 2 diabetes treated with 400 IU vitamin D per day for 14 weeks compared to placebo in a small RCT115Ghavamzadeh S, Mobasseri M, Mahdavi R. The effect of vitamin D supplementation on adiposity, blood glycated hemoglobin, serum leptin and tumor necrosis factor-α in type 2 diabetic patients. International Journal of Preventive Medicine. 2014 Sep;5(9):1091-8.
Increased immune system activation is not always beneficial, so your oncology team needs to determine whether immune activation would be favorable in your situation.
Preliminary evidence of balanced immune function among people with higher vitamin D levels
Preliminary evidence of balanced immune function among people treated with vitamin D
Vitamin D levels: preliminary evidence of balanced immune function among people with higher vitamin D levels
- Better response to influenza vaccines among people with prostate cancer with higher 25(OH)D3 levels compared to lower levels in a small 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 study116Chadha MK, Fakih M, Muindi J. Effect of 25-hydroxyvitamin D status on serological response to influenza vaccine in prostate cancer patients. Prostate. 2011 Mar 1;71(4):368-72.
- Down-regulation of the cytokine response, indicating an innate immune response, among healthy volunteers with seasonally elevated 1,25(OH)2D3 levels in summer compared to winter in a small observational study117Khoo AL, Chai LY et al. Regulation of cytokine responses by seasonality of vitamin D status in healthy individuals. Clinical & Experimental Immunology. 2011 Apr;164(1):72-9.
Vitamin D intake: preliminary evidence of balanced immune function among people treated with vitamin D
- Regulation of serum levels of a molecule that suppresses immune function (PD-L1) toward a midpoint after surgery among people with stage 1–3 digestive tract cancers treated with 2000 IU vitamin D3 per day compared to placebo in an additional analysis within 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 effects118Morita M, Okuyama M et al. Vitamin D supplementation regulates postoperative serum levels of PD-L1 in patients with digestive tract cancer and improves survivals in the highest quintile of PD-L1: a post hoc analysis of the AMATERASU randomized controlled trial. Nutrients. 2021 Jun 9;13(6):1987.
Good evidence of higher markers of inflammation among people with low 25(OH)D levels, typically below 10 ng/mL
Strong evidenceconsistent, significant effects in several large (or at least one very large) well designed clinical studies or at least two meta-analyses of clinical studies of moderate or better quality (or one large meta-analysis) finding similar results (this is the CancerChoices definition; other researchers and studies may define this differently) of lower markers of inflammation among people treated with vitamin D
Vitamin D levels: good evidence of higher markers of inflammation among people with low 25(OH)D levels, typically below 10 ng/mL
- A higher marker of inflammation (C-reactive protein, or CRP) among people with less than 12 ng/mL (30 nmol/L) 25(OH)D levels compared to 30 ng/mL (75 nmol/L) or higher 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 study119Ganji V, Tangpricha V, Zhang X. Serum vitamin D concentration ≥75 nmol/L is related to decreased cardiometabolic and inflammatory biomarkers, metabolic syndrome, and diabetes; and increased cardiorespiratory fitness in US adults. Nutrients. 2020 Mar 10;12(3):730.
- A lower marker of inflammation (CRP) with each 10 ng/mL increase in 25(OH)D among people with 25(OH)D levels below 21 ng/mL, but no evidence of an effect once 21 ng/mL was achieved and even an increase in CRP with each 10 ng/mL increase in 25(OH)D among people with 25(OH)D levels about 21 ng/mL in a very large observational study120Amer M, Qayyum R. Relation between serum 25-hydroxyvitamin D and C-reactive protein in asymptomatic adults (from the continuous National Health and Nutrition Examination Survey 2001 to 2006). American Journal of Cardiology. 2012 Jan 15;109(2):226-30.
- Higher markers of inflammation among people aged 51 to 77 years with low 25(OH)D3 levels compared to higher levels in a mid-sized observational study121Ngo DT, Sverdlov AL, McNeil JJ, Horowitz JD. Does vitamin D modulate asymmetric dimethylarginine and C-reactive protein concentrations? The American Journal of Medicine. 2010 Apr;123(4):335-41.
- Higher markers of inflammation (IL-6, CRP, and the ratios of IL-6 to IL-10 and CRP to IL-10) among people over age 60 with 25(OH)D levels below 10 ng/mL (25 nmol/L) compared to higher than 30 ng/mL (75 nmol/L) in a mid-sized observational study122Laird E, McNulty H et al. Vitamin D deficiency is associated with inflammation in older Irish adults. Journal of Clinical Endocrinology & Metabolism. 2014 May;99(5):1807-15.
- A higher marker of inflammation (CRP) among people with liver cancer (hepatocellular carcinoma) with lower 25(OH)D3 levels compared to higher levels in a mid-sized observational study123Finkelmeier F, Kronenberger B et al. Severe 25-hydroxyvitamin D deficiency identifies a poor prognosis in patients with hepatocellular carcinoma—a prospective cohort study. Alimentary Pharmacology & Therapeutics. 2014 May;39(10):1204-12.
- Lower markers of inflammation (hs-CRP, IL-6 and TNF-α) among people with obesity with higher 25(OH)D levels compared to lower levels in a mid-sized observational study124Bellia A, Garcovich C et al. Serum 25-hydroxyvitamin D levels are inversely associated with systemic inflammation in severe obese subjects. Internal and Emergency Medicine. 2013 Feb;8(1):33-40.
Vitamin D intake: strong evidence of lower markers of inflammation among people treated with vitamin D
- A lower marker of inflammation—high sensitivity C-reactive protein (hs-CRP)—among people with polycystic ovary syndrome treated with vitamin D compared to controls 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 18 RCTsrandomized 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 effects125Zhao JF, Li BX, Zhang Q. Vitamin D improves levels of hormonal, oxidative stress and inflammatory parameters in polycystic ovary syndrome: a meta-analysis study. Annals of Palliative Medicine. 2021 Jan;10(1):169-183.
- Lower levels of hs-CRP among people treated with vitamin D compared to controls in a meta-analysis of 10 RCTs126Chen N, Wan Z et al. Effect of vitamin D supplementation on the level of circulating high-sensitivity C-reactive protein: a meta-analysis of randomized controlled trials. Nutrients. 2014 Jun 10;6(6):2206-16.
- A very 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 lower CRP, 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. on TNF-α or IL-6 concentrations among people with overweight or obesity with vitamin D deficiency or insufficiency (undefined) treated with vitamin D compared to controls in a meta-analysis of 13 RCTs127Jamka M, Woźniewicz M et al. The effect of vitamin D supplementation on selected inflammatory biomarkers in obese and overweight subjects: a systematic review with meta-analysis. European Journal of Nutrition. 2016 Sep;55(6):2163-76.
- Lower hs-CRP among women with polycystic ovary syndrome treated with vitamin D compared to controls in a meta-analysis of 7 RCTs128Akbari M, Ostadmohammadi V et al. The effects of vitamin D supplementation on biomarkers of inflammation and oxidative stress among women with polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled trials. Hormone and Metabolic Research. 2018 Apr;50(4):271-279.
- A lower marker of inflammation (CRP) among people with a variety of health conditions treated with supplemental vitamin D compared to no supplementation in a review of 9 systematic reviews129Corrao S, Mallaci Bocchio R et al. Does evidence exist to blunt inflammatory response by nutraceutical supplementation during COVID-19 pandemic? An overview of systematic reviews of vitamin D, vitamin C, melatonin, and zinc. Nutrients. 2021;13(4):1261.
- A substantial decrease in a marker of inflammation (TNF-α) among people with type 2 diabetes treated with 400 IU vitamin D per day for 14 weeks compared to placebo in a small RCT130Ghavamzadeh S, Mobasseri M, Mahdavi R. The effect of vitamin D supplementation on adiposity, blood glycated hemoglobin, serum leptin and tumor necrosis factor-α in type 2 diabetic patients. International Journal of Preventive Medicine. 2014 Sep;5(9):1091-8.
- A lower marker of inflammation (hs-CRP) among women with grade 2 or 3 cervical intraepithelial neoplasia treated with 50,000 IU vitamin D3 every 2 weeks for 6 months compared to placebo in a small RCT131Vahedpoor Z, Mahmoodi S et al. Long-term vitamin D supplementation and the effects on recurrence and metabolic status of cervical intraepithelial neoplasia grade 2 or 3: a randomized, double-blind, placebo-controlled trial. Annals of Nutrition and Metabolism. 2018;72(2):151-160.
- A lower marker of inflammation (IL-6) during chemotherapy among people with colorectal cancer treated with 50,000 IU vitamin D3 in soft gel form weekly, either with or without 2 omega-3 fatty acids capsules daily, for 8 weeks compared to baseline in an uncontrolled analysisan analysis in which a therapy is used, but without a comparison group against which to judge outcomes within a small RCT132Haidari F, Abiri B, Iravani M, Ahmadi-Angali K, Vafa M. Randomized study of the effect of vitamin D and omega-3 fatty acids cosupplementation as adjuvant chemotherapy on inflammation and nutritional status in colorectal cancer patients. Journal of Dietary Supplements. 2020;17(4):384-400.
Strong evidence of lower markers of oxidative stressan imbalance between free radicals and antioxidants in your body; this imbalance can cause harmful oxidation reactions in your body chemistry among people, mostly with polycystic ovary syndrome, treated with vitamin D
- Better total antioxidant capacity (TAC), and malondialdehyde (MDA) levels among people with polycystic ovary syndrome treated with vitamin D compared to controls 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 18 RCTsrandomized 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 effects133Zhao JF, Li BX, Zhang Q. Vitamin D improves levels of hormonal, oxidative stress and inflammatory parameters in polycystic ovary syndrome: a meta-analysis study. Annals of Palliative Medicine. 2021 Jan;10(1):169-183.
- Lower markers of oxidative stress (MDA and TAC) among women with polycystic ovary syndrome treated with vitamin D compared to controls in a meta-analysis of 7 RCTs134Akbari M, Ostadmohammadi V et al. The effects of vitamin D supplementation on biomarkers of inflammation and oxidative stress among women with polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled trials. Hormone and Metabolic Research. 2018 Apr;50(4):271-279.
- Higher total antioxidant capacity among women with grade 2 or 3 cervical intraepithelial neoplasia treated with 50,000 IU vitamin D3 every 2 weeks for 6 months compared to placebo in a small RCT135Vahedpoor Z, Mahmoodi S et al. Long-term vitamin D supplementation and the effects on recurrence and metabolic status of cervical intraepithelial neoplasia grade 2 or 3: a randomized, double-blind, placebo-controlled trial. Annals of Nutrition and Metabolism. 2018;72(2):151-160.
Weak evidence of lower mammographic density among premenopausal women at high risk breast of cancer with a low baseline 25(OH)D level treated with vitamin D
Preliminary evidence of lower levels of a signaling protein related to the formation of new blood vessels among women with polycystic ovary syndrome treated with vitamin D
Mammographic density, a risk factor for breast cancer: weak evidence of lower mammographic density among premenopausal women at high risk breast of cancer with a low baseline 25(OH)D level treated with vitamin D
- 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 lower mammographic density at 24 months among premenopausal women at high risk breast of cancer with a baseline 25(OH)D level of 32 ng/mL or lower treated with 20,000 IU vitamin D per week for a year compared to placebo 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 effects136Crew KD, Anderson GL et al. Randomized double-blind placebo-controlled biomarker modulation study of vitamin D supplementation in premenopausal women at high risk for breast cancer (SWOG S0812). Cancer Prevention Research (Philadelphia). 2019 Jul;12(7):481-490.
VEGF levels, related to the formation of new blood vessels: preliminary evidence of lower levels of a signaling protein related to the formation of new blood vessels among women with polycystic ovary syndrome treated with vitamin D
- Lower VEGF levels, related to the formation of new blood vessels, among women with polycystic ovary syndrome treated with 50,000 IU oral vitamin D3 once a week for 8 weeks compared to placebo in a small RCT137Irani M, Seifer DB et al. Vitamin D decreases serum VEGF correlating with clinical improvement in vitamin D-deficient women with PCOS: a randomized placebo-controlled trial. Nutrients. 2017 Mar 28;9(4):334.
Preliminary evidence of lower markers of blood glucose, insulin imbalance, or inflammation among people treated with vitamin D and omega-3 fatty acids
Modest evidence of better blood sugar and insulin balance among people treated with both vitamin D and calcium
Weak evidence of better biomarkers of intestinal barrier function, which is related to risk of colorectal cancer, among people treated with calcium, with stronger effects among people with low 25(OH)D levels
Preliminary evidence of better markers of blood glucose and insulin among vitamin D-deficient women diagnosed with polycystic ovary syndrome treated with vitamin D, vitamin K, and calcium
No evidence of an effect on markers of blood glucose and insulin resistance during participation in progressive resistance training among adults aged 50–75 years with overweight or obesity and with type 2 diabetes treated with whey protein vitamin D3
Vitamin D and omega-3 fatty acids: preliminary evidence of lower markers of blood glucose, insulin imbalance, or inflammation among people treated with vitamin D and omega-3 fatty acids
- Lower fasting blood glucose, fasting insulin, and HOMA-IR among people with gestational diabetes treated with 40,000 IU vitamin D and 8,000 mg omega-3 fatty acids twice a day compared to placebo for 6 weeks 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 effects138Huang S, Fu J et al. The effect of combined supplementation with vitamin D and omega-3 fatty acids on blood glucose and blood lipid levels in patients with gestational diabetes. Annals of Palliative Medicine. 2021 May;10(5):5652-5658.
- Lower markers of inflammation (CRP and TNF-α) during chemotherapy among people with colorectal cancer treated with combined 50,000 IU vitamin D3 soft gel weekly and 2 omega-3 fatty acids capsules daily for 8 weeks compared to either vitamin D alone, omega-3s alone, or placebo in a small RCT139Haidari F, Abiri B, Iravani M, Ahmadi-Angali K, Vafa M. Randomized study of the effect of vitamin D and omega-3 fatty acids cosupplementation as adjuvant chemotherapy on inflammation and nutritional status in colorectal cancer patients. Journal of Dietary Supplements. 2020;17(4):384-400.
Vitamin D and calcium
Modest evidence of better blood sugar and insulin balance among people treated with both vitamin D and calcium
- Lower incidence of type 2 diabetes among people with the highest combined vitamin D and calcium 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 4 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 studies140Pittas AG, Lau J, Hu FB, Dawson-Hughes B. The role of vitamin D and calcium in type 2 diabetes. A systematic review and meta-analysis. Journal of Clinical Endocrinology and Metabolism. 2007 Jun;92(6):2017-29.
- Lower rise in fasting plasma glucose and a lower increase in HOMA-IR at 3 years among people with impaired fasting glucose but without diabetes at baseline treated with 500 mg calcium citrate and 700 IU vitamin D3 compared to placebo, but no evidence of an effect among people with normal fasting glucose at baseline in a mid-sized RCT141Pittas AG, Harris SS, Stark PC, Dawson-Hughes B. The effects of calcium and vitamin D supplementation on blood glucose and markers of inflammation in nondiabetic adults. Diabetes Care. 2007 Apr;30(4):980-6.
Weak evidence of better biomarkers of intestinal barrier function, which is related to risk of colorectal cancer, among people treated with calcium, with stronger effects among people with low 25(OH)D levels
- 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 better biomarkers of intestinal barrier function among people no more than 120 days after surgery for removal of a colorectal adenoma and with no remaining polyps after colonoscopy treated with 1,200 mg calcium daily for 1 year, whether with or without 1,000 IU vitamin D3, compared to no calcium, with stronger effects among people with 25(OH)D levels below 22.69 ng/mL compared to higher levels, in mid-sized analysis from an RCT142Mandle HB, Jahan FA et al. Effects of supplemental calcium and vitamin D on tight-junction proteins and mucin-12 expression in the normal rectal mucosa of colorectal adenoma patients. Molecular Carcinogenesis. 2019 Jul;58(7):1279-1290.
Vitamin D, vitamin K, and calcium: preliminary evidence of better markers of blood glucose and insulin balance among vitamin D-deficient women diagnosed with polycystic ovary syndrome treated with vitamin D, vitamin K, and calcium
- Better markers of blood glucose and insulin balance (serum insulin, homeostasis model of assessment-estimated insulin resistance, quantitative insulin sensitivity check index) among vitamin D-deficient women diagnosed with polycystic ovary syndrome aged 18-40 years treated with 500 mg calcium, 200 IU vitamin D, and 90 µg vitamin K for 8 weeks compared to placebo in a small RCT143Karamali M, Ashrafi M et al. The effects of calcium, vitamins D and K co-supplementation on markers of insulin metabolism and lipid profiles in vitamin D-deficient women with polycystic ovary syndrome. Experimental and Clinical Endocrinology & Diabetes. 2017 May;125(5):316-321.
Vitamin D and whey protein: no evidence of an effect on markers of blood glucose and insulin resistance during participation in progressive resistance training among adults aged 50–75 years with overweight or obesity and with type 2 diabetes treated with whey protein and vitamin D3 in one trial
- No evidence of an effect on markers of blood glucose and insulin resistance (HbA1c and HOMA2-IR) 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 RCT144Miller 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.
Managing side effects and promoting wellness
Is vitamin D linked to fewer or less severe side effects or symptoms? Is it linked to less toxicity from cancer treatment? Does it support your quality of life or promote general well-being? We present the evidence.
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 more lymphoma-related symptoms among people with low levels of 25(OH)D
Weak evidence of fewer endocrine symptoms and less bone pain and fatigue among clinically stable women with estrogen receptor-positive metastatic breast cancer and insufficient serum 25-hydroxyvitamin D levels treated with high-dose repletion therapy
Weak evidence of more lymphoma-related symptoms among people with low levels of 25(OH)D
- 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 incidence of lymphoma-related symptoms among people with previously untreated lymphoma with low levels of 25(OH)D (variably defined across studies) compared to higher 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 studies145Tao Y, Chen H, Zhou Y, Shi Y. Meta-analysis of the prognostic and clinical value of serum 25-hydroxyvitamin D levels in previously untreated lymphoma. Future Oncology. 2021 May;17(14):1825-1838.
Weak evidence of fewer endocrine symptoms and less bone pain and fatigue among clinically stable women with estrogen receptor-positive metastatic breast cancer and insufficient serum 25-hydroxyvitamin D levels treated with high-dose repletion therapy
- 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 fewer endocrine symptoms and less bone pain and fatigue among clinically stable women with estrogen receptor-positive metastatic breast cancer and insufficient serum 25-hydroxyvitamin D levels treated with high-dose repletion therapy for 8 weeks compared to baseline in a small uncontrolled triala study in which a therapy is used, but without a comparison group against which to judge outcomes; an uncontrolled trial is considered a weak study design146Sheean PM, Robinson P et al. Associations between cholecalciferol supplementation and self-reported symptoms among women with metastatic breast cancer and vitamin d deficiency: a pilot study. Oncology Nursing Forum. 2021 May 1;48(3):352-360.
Weak evidence of increased weight, body mass index (BMI), and fat-free mass (FFM) during chemotherapy among people with colorectal cancer treated with vitamin D
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 better muscle function among people with prostate cancer treated with vitamin D
Weak evidence of increased weight, body mass index (BMI), and fat-free mass (FFM) during chemotherapy among people with colorectal cancer treated with vitamin D
- Increased weight, body mass index (BMI), and fat-free mass (FFM) during chemotherapy among people with colorectal cancer treated with 50,000 IU vitamin D3 soft gel weekly, either with or without 660mg omega-3 fatty acid supplements daily, for 8 weeks compared to baseline in an uncontrolled analysisan analysis in which a therapy is used, but without a comparison group against which to judge outcomes within a small 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 effects147Haidari F, Abiri B, Iravani M, Ahmadi-Angali K, Vafa M. Randomized study of the effect of vitamin D and omega-3 fatty acids cosupplementation as adjuvant chemotherapy on inflammation and nutritional status in colorectal cancer patients. Journal of Dietary Supplements. 2020;17(4):384-400.
Preliminary evidence of better muscle function among people with prostate cancer treated with vitamin D
- A better marker of muscle health (bioelectrical impedance) among people aged 60 or older with prostate cancer treated with 600 IU/day plus 50,000 IU/week vitamin D compared to 600 IU/day plus placebo weekly for 24 weeks in a small RCT148Inglis JE, Fernandez ID et al. Effects of High-Dose Vitamin D Supplementation on Phase Angle and Physical Function in Patients with Prostate Cancer on ADT. Nutrition and Cancer. 2021;73(10):1882-1889.
- Better muscle strength among 37% of people with advanced hormone refractory prostate cancer treated with 2,000 units oral vitamin D daily for 12 weeks compared to baseline in a small uncontrolled triala study in which a therapy is used, but without a comparison group against which to judge outcomes; an uncontrolled trial is considered a weak study design149Van Veldhuizen PJ, Taylor SA, Williamson S, Drees BM. Treatment of vitamin D deficiency in patients with metastatic prostate cancer may improve bone pain and muscle strength. Journal of Urology. 2000 Jan;163(1):187-90.
Preliminary evidence of less loss of bone mineral density during hormone therapy among people with cancer treated with high amounts of vitamin D
Loss of bone density and impacts on teeth and bones is a common side effect of treatment with systemic corticosteroids, exemestane, or androgen deprivation therapy. Also see clinical practice guidelines relating to bone health in Are you a health professional? ›
- A weak trend toward less loss of bone mineral density at the femoral neck during treatment with adjuvant anastrozole among women with early breast cancer and aromatase inhibitor-induced musculoskeletal symptoms treated with 50,000 IU vitamin D2 capsules weekly, converting to monthly depending on baseline 25(OH)D levels, compared to placebo in a small RCT150Rastelli AL, Taylor ME et al. Vitamin D and aromatase inhibitor-induced musculoskeletal symptoms (AIMSS): a phase II, double-blind, placebo-controlled, randomized trial. Breast Cancer Research and Treatment. 2011 Aug;129(1):107-16.
- Substantially lower total hip bone loss and a weak trend toward less femoral neck and trochanter bone loss, but no evidence of an effect on lumbar spine bone loss, within 6 months of starting androgen deprivation therapy (ADT) and with 6 more planned months of ADT among people 60 years or older with prostate cancer and with 25(OH)D levels below 32 ng/ml treated with supplemental 600 IU/daily vitamin D plus 1,000 mg/day calcium further treated with high-dose 50,000 IU/weekly vitamin D compared to placebo for 24 weeks in a small RCT151Peppone LJ, Mustian KM et al. A phase II RCT of high-dose vitamin D supplementation for androgen deprivation therapy (ADT)-induced bone loss among older prostate cancer (PCa) patients. Journal of Clinical Oncology 35, 10113–10113, 2017.
Preliminary evidence of less fatigue among people with advanced cancer treated with vitamin D
- Less fatigue among people with advanced cancer admitted to palliative care and with 25(OH)D levels less than 20 ng/mL (50 nmol/L) treated with 4000 IU vitamin D/day for 12 weeks compared to placebo 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 effects152Helde Frankling M, Klasson C et al. ‘Palliative-D’—vitamin D supplementation to palliative cancer patients: a double blind, randomized placebo-controlled multicenter trial. Cancers (Basel). 2021 Jul 23;13(15):3707.
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 a link between lower 25(OH)D levels and more chemotherapy-induced peripheral neuropathy (CIPN) among people with cancer
- Lower 25(OH)D levels among people with cancer with more severe (grade 2–3) chemotherapy-induced peripheral neuropathy (CIPN) compared to grade 0–1 CIPN in all 4 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 analyzed in a review153Tofthagen C, Tanay M et al. A systematic review of nutritional lab correlates with chemotherapy induced peripheral neuropathy. Journal of Clinical Medicine. 2022 Jan 12;11(2):355.
Preliminary evidence of substantially less oral mucositisinflammation and ulceration of the mucous membranes lining the digestive tract, usually as an adverse effect of chemotherapy and radiotherapy treatment for cancer during radiotherapy among people with head and neck cancer treated with a topical oral vitamin D gel
- Substantially less oral mucositis during radiotherapy among people with head and neck cancer treated with a topical oral vitamin D gel, either with or without conventional treatment for oral mucositis, compared to no vitamin D in a small 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 effects154Bakr IS, Zaki AM, El-Moslemany RM, Elsaka RO. Vitamin D oral gel for prevention of radiation-induced oral mucositis: a randomized clinical trial. Oral Diseases. 2021 Jul;27(5):1197-1204.
Preliminary evidence of less opioid use among people with advanced cancer with 25(OH)D levels less than 20 ng/mL treated with vitamin D
Modest evidence of lower pain during hormone therapy among people treated with vitamin D, and especially among people starting with lower 25(OH)D levels
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. on pain after brain tumor surgery among people with vitamin D serum levels of 20 ng/dL or lower treated with vitamin D before surgery in a small study
Preliminary evidence of less pain after colorectal cancer surgery among people with sufficient vitamin D levels
General cancer pain: preliminary evidence of less opioid use among people with advanced cancer with 25(OH)D levels less than 20 ng/mL treated with vitamin D
- Moderately smaller increase of opioid (fentanyl) use among people with advanced cancer admitted to palliative care and with 25(OH)D levels less than 20 ng/mL (50 nmol/L) treated with 4000 IU vitamin D/day for 12 weeks compared to placebo 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 effects155Helde Frankling M, Klasson C et al. ‘Palliative-D’—vitamin D supplementation to palliative cancer patients: a double blind, randomized placebo-controlled multicenter trial. Cancers (Basel). 2021 Jul 23;13(15):3707.
Pain related to hormone therapy: modest evidence of lower pain during hormone therapy among people treated with vitamin D, and especially among people starting with lower 25(OH)D levels
- Lower scores on Brief Pain Inventory and a weak trend toward fewer aromatase inhibitor-associated musculoskeletal symptoms among women with stage 1–3 breast cancer starting adjuvant letrozole and with 25(OH)D levels of 40 ng/mL or lower treated with standard daily supplement of 1200 mg calcium and 600 IU vitamin D3 further receiving 30,000 IU oral vitamin D compared to the standard supplement and placebo in a mid-sized RCT156Khan QJ, Kimler BF, et al. Randomized trial of vitamin D3 to prevent worsening of musculoskeletal symptoms in women with breast cancer receiving adjuvant letrozole. The VITAL trial. Breast Cancer Research and Treatment. 2017 Nov;166(2):491-500.
- Lower measures of pain and pain interference at 2 months during treatment with adjuvant anastrozole, with stronger effects among women with lower baseline 25(OH)D levels, among women with early breast cancer and aromatase inhibitor-induced musculoskeletal symptoms treated with 50,000 IU vitamin D2 capsules weekly, converting to monthly treatment depending on baseline 25(OH)D levels, compared to placebo in a small RCT157Rastelli AL, Taylor ME et al. Vitamin D and aromatase inhibitor-induced musculoskeletal symptoms (AIMSS): a phase II, double-blind, placebo-controlled, randomized trial. Breast Cancer Research and Treatment. 2011 Aug;129(1):107-16.
- Less disability from joint pain after 16 weeks of letrozole among women initiating adjuvant letrozole for breast cancer with baseline 25(OH)D levels of 40 ng/mL or less treated for 4 weeks with standard dose calcium and vitamin D, then further treated with 50,000 IU per week for 12 weeks and achieving 25(OH)D levels higher than 66 ng/mL compared to lower levels in a small RCT158Khan QJ, Reddy PS et al. Effect of vitamin D supplementation on serum 25-hydroxy vitamin D levels, joint pain, and fatigue in women starting adjuvant letrozole treatment for breast cancer. Breast Cancer Research and Treatment. 2010 Jan;119(1):111-8.
- A smaller increase in joint pain among women starting aromatase inhibitor therapy who attained concentrations of 25(OH)D of 40 ng/mL or higher through supplementation compared to lower 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 study159Prieto-Alhambra D, Javaid MK et al. Vitamin D threshold to prevent aromatase inhibitor-induced arthralgia: a prospective cohort study. Breast Cancer Research and Treatment. 2011 Feb;125(3):869-78.
- Comparable effects on aromatase inhibitor-associated musculoskeletal symptoms including general musculoskeletal pain, joint pain, and muscle stiffness among postmenopausal women with stage 1–3a breast cancer treated with either 600 IU or 4000 IU vitamin D3 daily for 6 months, and so no evidence of added benefit from the higher dose, in a mid-sized uncontrolled trial160Shapiro AC, Adlis SA et al. Randomized, blinded trial of vitamin D3 for treating aromatase inhibitor-associated musculoskeletal symptoms (AIMSS). Breast Cancer Research and Treatment. 2016 Feb;155(3):501-12.
- No evidence of an effect on development of joint pain (arthralgia), although higher serum vitamin D levels were achieved, during adjuvant aromatase inhibitor therapy among postmenopausal women treated with 50,000 IU vitamin D3 weekly for 12 weeks followed by 2000 IU daily for 40 weeks compared to 800 IU daily for 52 weeks in a small RCT161Niravath P, Hilsenbeck SG et al. Randomized controlled trial of high-dose versus standard-dose vitamin D3 for prevention of aromatase inhibitor-induced arthralgia. Breast Cancer Research and Treatment. 2019 Sep;177(2):427-435.
- Lower pain scores among 25% of people with advanced hormone refractory prostate cancer treated with 2,000 units oral vitamin D daily for 12 weeks compared to baseline in a small uncontrolled trial162Van Veldhuizen PJ, Taylor SA, Williamson S, Drees BM. Treatment of vitamin D deficiency in patients with metastatic prostate cancer may improve bone pain and muscle strength. Journal of Urology. 2000 Jan;163(1):187-90.
Pain related to surgery
No evidence of an effect on pain after brain tumor surgery among people with vitamin D serum levels of 20 ng/dL or lower treated with vitamin D before surgery in a small study
Preliminary evidence of less pain after colorectal cancer surgery among people with sufficient vitamin D levels
- No evidence of an effect on pain, although higher serum vitamin D levels were achieved, after brain tumor surgery among people with vitamin D serum levels of 20 ng/dL or lower treated with an intramuscular injection of 300,000 IU vitamin D before surgery compared to no treatment in a small RCT163Hajimohammadebrahim-Ketabforoush M, Shahmohammadi M, Khoundabi B, Shariatpanahi ZV. Effect of vitamin D supplementation on postcraniotomy pain after brain tumor surgery: a randomized clinical trial. World Neurosurgery. 2019 Oct;130:e105-e111.
- Lower pain threshold, opioid and analgesic use, and pain scores after colorectal cancer surgery among people with sufficient vitamin D levels (20 ng/mL or higher) compared to deficient levels (less than 20 ng/mL) in a mid-sized observational study164Xia J, Li D, Yu G, et al. Effects of hypovitaminosis D on preoperative pain threshold and perioperative opioid use in colorectal cancer surgery: a cohort study. Pain Physician. 2022;25(7):E1009-E1019.
Preliminary evidence of higher levels of self-reported health-related quality of life among women with breast cancer either taking vitamin D supplements or with sufficient vitamin D levels
- Higher levels of self-reported health-related quality of life at study enrollment and 6 months later among women with breast cancer taking vitamin D supplements compared to no supplements 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 study165Andersen MR, Sweet E et al. Effects of vitamin D use on health-related quality of life of breast cancer patients in early survivorship. Integrative Cancer Therapies. 2019 Jan-Dec;18:1534735418822056.
- Higher levels of self-reported health-related quality of life 6 months after study enrollment among women with breast cancer with sufficient vitamin D levels (30 ng/mL or higher) compared to lower levels in a mid-sized observational study166Andersen MR, Sweet E et al. Effects of vitamin D use on health-related quality of life of breast cancer patients in early survivorship. Integrative Cancer Therapies. 2019 Jan-Dec;18:1534735418822056.
Preliminary evidence of less vaginal atrophy during tamoxifen treatment among women with breast cancer treated with vaginal vitamin D suppositories
- Less vaginal atrophy during tamoxifen treatment among women with breast cancer treated with vaginal vitamin D suppositories every evening before bedtime for 8 weeks compared to placebo 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 effects167Keshavarzi Z, Janghorban R, Alipour S, Tahmasebi S, Jokar A. The effect of vitamin D and E vaginal suppositories on tamoxifen-induced vaginal atrophy in women with breast cancer. Supportive Care in Cancer. 2019 Apr;27(4):1325-1334
Preliminary evidence of higher severity of radiation-induced acute proctitis among people with vitamin D deficiency
- Higher severity of radiation-induced acute proctitis after 5 weeks of radiation therapy among people with vitamin D deficiency (less than 14 ng/mL or 35 nmol/L for males and less than 16 ng/mL or 40 nmol/L in for females) compared to higher levels in a small 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 study168Ghorbanzadeh-Moghaddam A, Gholamrezaei A, Hemati S. Vitamin D deficiency is associated with the severity of radiation-induced proctitis in cancer patients. International Journal of Radiation Oncology, Biology, Physics. 2015 Jul 1;92(3):613-8.
No evidence of an effect on markers of vascular health among people with chronic fatigue syndrome treated with vitamin D
Modest evidence of lower incidence of dementia and longer dementia-free survival among people taking vitamin D supplements prior to dementia onset
Strong evidence of less negative emotion or fewer symptoms of depression among people with clinically significant depressive symptoms or depressive disorder treated with vitamin D
Insufficient (conflicting) evidence of an effect on fatigue among people with fatigue treated with vitamin D
Preliminary evidence of less severe peripheral neuropathy among people with diabetes and neuropathy treated with vitamin D
Good evidence of fewer requests for pain medication but no evidence of an effect on pain scores overall among people with vitamin D levels below 20 ng/mL treated with vitamin D
Cardiovascular symptoms: 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. on markers of vascular health among people with chronic fatigue syndrome treated with vitamin D
- No evidence of an effect on markers of vascular health (stiffness measured using carotid-femoral pulse wave velocity, dilatation of the brachial artery, blood pressure, or cholesterol) among people with chronic fatigue syndrome treated with 100,000 IU oral vitamin D3 every 2 months for 6 months compared to placebo in a small 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 effects169Witham MD, Adams F et al. Effect of intermittent vitamin D3 on vascular function and symptoms in chronic fatigue syndrome–a randomised controlled trial. Nutrition, Metabolism & Cardiovascular Diseases. 2015 Mar;25(3):287-94.
Cognitive difficulties: modest evidence of lower incidence of dementia and longer dementia-free survival among people taking vitamin D supplements prior to dementia onset
- Lower incidence of dementia and longer dementia-free survival among people taking vitamin D supplements prior to dementia onset 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 study170Ghahremani M, Smith EE et al. Vitamin D supplementation and incident dementia: effects of sex, APOE, and baseline cognitive status. Alzheimers & Dementia (Amsterdam). 2023 Mar 1;15(1):e12404.
Depression or negative emotions: strong evidenceconsistent, significant effects in several large (or at least one very large) well designed clinical studies or at least two meta-analyses of clinical studies of moderate or better quality (or one large meta-analysis) finding similar results (this is the CancerChoices definition; other researchers and studies may define this differently) of less negative emotion or fewer symptoms of depression among people with clinically significant depressive symptoms or depressive disorder treated with vitamin D
- Less negative emotion among people with major depressive disorder or with 25(OH)D levels less than 20 ng/mL (50 nmol/L) treated with up to 4,000 IU vitamin D per day for 8 weeks or longer compared to controls 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 25 RCTsrandomized 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 effects171Cheng YC, Huang YC, Huang WL. The effect of vitamin D supplement on negative emotions: a systematic review and meta-analysis. Depression and Anxiety. 2020 Jun;37(6):549-564.
- Moderately lower depressive symptom ratings among people with major depression treated with vitamin D compared to controls in a meta-analysis of 4 RCTs172Vellekkatt F, Menon V. Efficacy of vitamin D supplementation in major depression: a meta-analysis of randomized controlled trials. Journal of Postgraduate Medicine. Apr-Jun 2019;65(2):74-80.
- Moderately fewer depressive symptoms among people with clinically significant depressive symptoms or depressive disorder, but no evidence of an effect among people without clinically significant depression, treated with vitamin D compared to controls in a meta-analysis of 2 RCTs173Shaffer JA, Edmondson D et al. Vitamin D supplementation for depressive symptoms: a systematic review and meta-analysis of randomized controlled trials. Psychosomatic Medicine. 2014 Apr;76(3):190-6.
Fatigue: insufficient evidencepreclinical evidence only OR clinical studies with such poor or unclear methodology that no conclusion can be drawn OR conflicting findings across clinical studies with no preponderance of evidence in one direction; conflicting evidence occurs when studies find conflicting effects (positive effect vs no effect or negative effect) with the same treatment and the same general study population (same cancer type, for example) (this is the CancerChoices definition; other researchers and studies may define this differently) of an effect on fatigue among people with fatigue treated with vitamin D
- Lower fatigue scores 4 weeks after treatment among people with fatigue and 25(OH)D levels less than 8 ng/mL (20 nmol/L) treated with a single 100,000 IU oral dose of vitamin D3 compared to placebo, and lower fatigue scores related to rises in 25(OH)D levels, in a mid-sized RCT174Nowak A, Boesch L et al. Effect of vitamin D3 on self-perceived fatigue: a double-blind randomized placebo-controlled trial. Medicine (Baltimore). 2016 Dec;95(52):e5353.
- No evidence of an effect on fatigue scores among people with chronic fatigue syndrome treated with 100,000 IU oral vitamin D3 every 2 months for 6 months compared to placebo in a small RCT175Witham MD, Adams F et al. Effect of intermittent vitamin D3 on vascular function and symptoms in chronic fatigue syndrome–a randomised controlled trial. Nutrition, Metabolism & Cardiovascular Diseases. 2015 Mar;25(3):287-94.
Neurological symptoms: preliminary evidence of less severe peripheral neuropathy among people with diabetes and neuropathy treated with vitamin D
- Less severe peripheral neuropathy among people with diabetes and neuropathy treated with 40,000 IU vitamin D (cholecalciferol) per week for 24 weeks compared to 5000 IU per week in a small RCT176Karonova T, Stepanova A, Bystrova A, Jude EB. High-dose vitamin D supplementation improves microcirculation and reduces inflammation in diabetic neuropathy patients. Nutrients. 2020 Aug 20;12(9):2518.
Pain: 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 fewer requests for pain medication but no evidence of an effect on pain scores overall among people with vitamin D levels below 20 ng/mL treated with vitamin D
- No evidence of an effect on pain scores among people treated with monthly 100,000-IU capsules of vitamin D3 over roughly 3 years compared to placebo, but fewer requests for nonsteroidal anti-inflammatory drugs among people with vitamin D levels below 20 ng/mL (50 nmol/L) compared to higher levels in a very large RCT177Wu Z, Camargo CA Jr et all. Monthly vitamin D supplementation, pain, and pattern of analgesic prescription: secondary analysis from the randomized, double-blind, placebo-controlled Vitamin D Assessment study. Pain. 2018 Jun;159(6):1074-1082.
No evidence of an effect on bone mineral density during androgen deprivation therapy among people with prostate cancer or among adolescents with acute lymphoblastic leukemia treated with vitamin D and calcium in several clinical trials
Weak evidence of only slight decline in bone mineral density during conventional or hypofractionated radiation therapy among people with prostate cancer treated with luteinizing hormone-releasing hormone agonist, calcium, and vitamin D3
Good evidence of lower incidence of vertebral fractures but no evidence of an effect on incidence of hip fracture among postmenopausal women treated with calcium plus vitamin D
Preliminary evidence of lower rates of fungal infection, hemorrhage, or macrophage activation syndrome among people with acute myeloid leukemia treated with supplemental vitamin C and vitamin D
No evidence of an effect on mood scores, risk of depression incidence or recurrence, or clinically relevant depressive symptoms among people without depression treated with vitamin D and fish oil in a very large study
Preliminary evidence of better mood and less depression among women with symptoms of mild to moderate depression treated with a brisk 20-minute outdoor walk at target heart rate of 60% of maximum heart rate, increased light exposure throughout the day, and a vitamin regimen
Preliminary evidence of better markers of bone metabolism during chemotherapy among children with acute lymphoblastic leukemia treated with vitamin K2 and vitamin D3
Preliminary evidence of less diabetic peripheral neuropathy among people treated with DiVFuSS formulation
Preliminary evidence of less severe numbness, jolting pain, and irritation among people with diabetic peripheral neuropathy treated with QR-333
Vitamin D and calcium
No evidence of an effect on bone mineral density during androgen deprivation therapy among people with prostate cancer or among adolescents with acute lymphoblastic leukemia treated with vitamin D and calcium in several clinical trials
- No evidence of an effect on loss of bone mineral density during androgen deprivation therapy among men with prostate cancer treated the doses commonly recommended—500-1,000 mg calcium and 200-500 IU vitamin D per day—compared to no vitamin D, no calcium, or neither, in a review of 12 clinical trials. Study authors’ note: “high levels of dietary calcium and calcium supplement use are associated with higher risks for cardiovascular disease and advanced prostate cancer,” and so higher supplementation cannot currently be recommended for men in treatment for prostate cancer178Datta M, Schwartz GG. Calcium and vitamin D supplementation during androgen deprivation therapy for prostate cancer: a critical review. Oncologist. 2012;17(9):1171-9.
- No evidence of an effect on bone density among adolescents with acute lymphoblastic leukemia treated with intermittent high-dose vitamin D3 and 1,000mg daily oral calcium citrate compared to placebo in a small RCT179Orgel E, Mueske NM et al. A randomized controlled trial testing an adherence-optimized Vitamin D regimen to mitigate bone change in adolescents being treated for acute lymphoblastic leukemia. Leukemia and Lymphoma. 2017 Oct;58(10):2370-2378.
Weak evidence of only slight decline in bone mineral density during conventional or hypofractionated radiation therapy among people with prostate cancer treated with luteinizing hormone-releasing hormone agonist, calcium, and vitamin D3
- Slight (3.2%) declines in bone mineral density at 30 months, with no decline in bone mineral density category in 83% of people, during conventional or hypofractionated radiation therapy among people with localized high-risk prostate cancer treated with 28 months of luteinizing hormone-releasing hormone agonist, 500 mg calcium, and 400 IU vitamin D3 twice a day compared to baseline in an uncontrolled analysisan analysis in which a therapy is used, but without a comparison group against which to judge outcomes of 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 effects;180Khriguian J, Tsui JMG et al. The clinical significance of bone mineral density changes following long-term androgen deprivation therapy in localized prostate cancer patients. Journal of Urology. 2021 Jun;205(6):1648-1654. people treated with hormonal therapy for prostate cancer, such as in this study, are at great risk for bone loss, osteoporosis, and bone fractures181Suarez-Almazor ME, Pundole X et al. Association of bone mineral density testing with risk of major osteoporotic fractures among older men receiving androgen deprivation therapy to treat localized or regional prostate cancer. JAMA Network Open. 2022 Apr 1;5(4):e225432; Hormone Therapy for Prostate Cancer. What are the side effects of hormone therapy for prostate cancer? National Cancer Institute. February 22, 2021. Viewed July 20, 2022.
Good evidence of lower incidence of vertebral fractures but no evidence of an effect on incidence of hip fracture among postmenopausal women treated with calcium plus vitamin D
- Lower incidence of vertebral fractures but no evidence of an effect on incidence of hip fracture among postmenopausal women treated with calcium plus vitamin D compared to placebo in a very large RCT182Cauley 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.
Vitamin C and vitamin D supplements: preliminary evidence of lower rates of fungal infection, hemorrhage, or macrophage activation syndrome among people with acute myeloid leukemia treated with supplemental vitamin C and vitamin D
- Lower rates of fungal infection, hemorrhage, or macrophage activation syndrome among those treated with supplemental vitamin C and vitamin D from day 10 of chemotherapy until hematologic recovery from induction and consolidation compared to no supplementation 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 study183Mouchel PL, Bérard E et al. Vitamin C and D supplementation in acute myeloid leukemia. Blood Advances. 2023 Sep 6:bloodadvances.2023010559.
Vitamin D and omega-3 fatty acids: no evidence of an effect on mood scores, risk of depression incidence or recurrence, or clinically relevant depressive symptoms among people without depression treated with vitamin D and fish oil in a very large study
- No evidence of an effect on mood scores, risk of depression incidence or recurrence, or clinically relevant depressive symptoms over more than 5 years among people without depression treated with 2000 IU cholecalciferol and fish oil per day compared to placebo in a very large RCT184Okereke OI, Reynolds CF 3rd et al. Effect of long-term vitamin D3 supplementation vs placebo on risk of depression or clinically relevant depressive symptoms and on change in mood scores: a randomized clinical trial. Journal of the American Medical Association. 2020 Aug 4;324(5):471-480.
Vitamin D with outdoor walking, light exposure, and several other vitamins: preliminary evidence of better mood and less depression among women with symptoms of mild to moderate depression treated with a brisk 20-minute outdoor walk at target heart rate of 60% of maximum heart rate, increased light exposure throughout the day, and a vitamin regimen
- Higher measures of overall mood, self-esteem, and general sense of well-being and fewer symptoms on two measures of depression among women with symptoms of mild to moderate depression not taking any mood-altering medication and treated with a brisk 20-minute outdoor walk, increased light exposure throughout the day, and a vitamin regimen of vitamin B1 (thiamine), vitamin B6 (pyroxidine), vitamin B2 (riboflavin), folic acid, selenium, and 400 IU vitamin D compared to a placebo vitamin in a mid-sized RCT185Brown MA, Goldstein-Shirley J, Robinson J, Casey S. The effects of a multi-modal intervention trial of light, exercise, and vitamins on women’s mood. Women Health. 2001;34(3):93-112.
Vitamin D and vitamin K: preliminary evidence of better markers of bone metabolism during chemotherapy among children with acute lymphoblastic leukemia treated with vitamin K2 and vitamin D3
- Better markers of bone metabolism during chemotherapy among children with acute lymphoblastic leukemia treated with 100 mcg vitamin K2 (menaquinone-7) and 10 mcg vitamin D3 (calcitriol) compared to chemotherapy alone in a small RCT186Solmaz I, Ozdemir MA et al. Effect of vitamin K2 and vitamin D3 on bone mineral density in children with acute lymphoblastic leukemia: a prospective cohort study. Journal of Pediatric Endocrinology & Metabolism. 2021 Feb 25;34(4):441-447.
DiVFuSS formulation of vitamins C, D3, and E (d-α tocopherol), zinc oxide, eicosapentaenoic acid, docosahexaenoic acid, α-lipoic acid (racemic mixture), coenzyme Q10, mixed tocotrienols/tocopherols, zeaxanthin, lutein, benfotiamine, N-acetyl cysteine, grape seed extract, resveratrol, turmeric root extract, green tea leaf, and Pycnogenol: preliminary evidence of less diabetic peripheral neuropathy among people treated with DiVFuSS formulation
- Less diabetic peripheral neuropathy among people treated with DiVFuSS formulation for 6 months compared to placebo in a small RCT187Chous AP, Richer SP, Gerson JD, Kowluru RA. The Diabetes Visual Function Supplement Study (DiVFuSS). British Journal of Ophthalmology. 2016 Feb;100(2):227-34.
QR-333, a topical compound containing quercetin, ascorbyl palmitate, and vitamin D3: preliminary evidence of less severe numbness, jolting pain, and irritation among people with diabetic peripheral neuropathy treated with QR-333
- Less severe numbness, jolting pain, and irritation among people with diabetic peripheral neuropathy treated with QR-333 3 times daily for 4 weeks compared to placebo in a small RCT188Valensi P, Le Devehat C et al. A multicenter, double-blind, safety study of QR-333 for the treatment of symptomatic diabetic peripheral neuropathy. A preliminary report. Journal of Diabetes Complications. 2005 Sep-Oct;19(5):247-53.
Reducing cancer risk
Is vitamin D linked to lower risks of developing cancer or of recurrence? We present the evidence.
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 lower risk of cancer among people with higher 25(OH)D levels
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 lower cancer mortality among people without cancer at baseline with higher 25(OH)D levels
Strong evidenceconsistent, significant effects in several large (or at least one very large) well designed clinical studies or at least two meta-analyses of clinical studies of moderate or better quality (or one large meta-analysis) finding similar results (this is the CancerChoices definition; other researchers and studies may define this differently) of slightly lower cancer mortality among people without cancer at baseline taking vitamin D supplements
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 lower risk of cancer among healthy adults aged 70 years or older taking vitamin D supplements
Vitamin D levels
Weak evidence of lower risk of cancer among people with higher 25(OH)D levels
- 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 lower risk of cancer among people with higher 25(OH)D levels compared to lower levels, and a 7% lower risk with each 8 ng/mL (20 nmol/L) increase of 25(OH)D 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 8 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 studies189Han J, Guo X et al. 25-hydroxyvitamin D and total cancer incidence and mortality: a meta-analysis of prospective cohort studies. Nutrients. 2019 Sep 26;11(10):2295.
Good evidence of lower cancer mortality among people without cancer at baseline with higher 25(OH)D levels
- Lower cancer mortality among people without cancer at baseline with higher 25(OH)D levels compared to lower levels, and 2% lower mortality with each 8 ng/mL (20 nmol/L) increase of 25(OH)D levels, in a very large meta-analysis of 16 observational studies190Han J, Guo X et al. 25-hydroxyvitamin D and total cancer incidence and mortality: a meta-analysis of prospective cohort studies. Nutrients. 2019 Sep 26;11(10):2295.
Vitamin D intake
Strong evidence of slightly lower cancer mortality among people without cancer at baseline taking vitamin D supplements
- 15% lower cancer mortality among people without cancer at baseline taking vitamin D supplements compared to no supplements in a large meta-analysis of 50 RCTsrandomized 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 effects191Zhang Yu, Fang F et al. Association between vitamin D supplementation and mortality: systematic review and meta-analysis. British Medical Journal. 2019 Aug 12;366:l4673.
- Slightly lower cancer mortality but no evidence of lower risk of cancer among people without cancer at baseline taking vitamin D supplements compared to placebo in a large meta-analysis of 10 RCTs192Zhang X, Niu W. Meta-analysis of randomized controlled trials on vitamin D supplement and cancer incidence and mortality. Bioscience Reports. 2019 Nov 29;39(11).
- Slightly lower cancer mortality (5 studies), but no evidence of an effect on cancer incidence (10 studies) among people without cancer at baseline taking supplements and attaining 25(OH)D levels of 22-54 ng/mL (54–135 of nmol/L) compared to controls not taking supplements, with effects from daily dosing but not from infrequent bolus dosing in meta-analyses of RCTs193Keum N, Lee DH, Greenwood DC, Manson JE, Giovannucci E. Vitamin D supplementation and total cancer incidence and mortality: a meta-analysis of randomized controlled trials. Annals of Oncology. 2019 May 1;30(5):733-743.
- A weak trend toward lower cancer mortality after the study period ended among people without cancer at baseline taking vitamin D supplements, but otherwise no evidence of an effect of supplementation on cancer mortality in a large meta-analysis of 30 RCTs194Goulão B, Stewart F, Ford JA, MacLennan G, Avenell A. Cancer and vitamin D supplementation: a systematic review and meta-analysis. American Journal of Clinical Nutrition. 2018 Apr 1;107(4):652-663.
- Slightly lower cancer mortality but no evidence of an effect on cancer risk among people without cancer at baseline taking vitamin D3 compared to controls in a large meta-analysis of 56 RCTs195Bjelakovic G, Gluud LL et al. Vitamin D supplementation for prevention of mortality in adults. Cochrane Database of Systematic Reviews. 2014 Jan 10;(1):CD007470.
- A weak trend toward lower cancer mortality, with larger effects at longer latencies, but no evidence of an effect on risk of invasive cancer, among people without cancer at baseline taking vitamin D supplements compared to no supplements in a very large RCT196Manson 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. Journal of Steroid Biochemistry and Molecular Biology. 2020 Apr;198:105522.
Modest evidence of lower risk of cancer among healthy adults aged 70 years or older taking vitamin D supplements
- 26% lower risk of cancer as a whole among healthy community-dwelling adults aged 70 years or older taking 2000 IU supplemental vitamin D3 per day compared to placebo in a large RCT; even greater reductions were found when vitamin D was combined with “a simple home strength exercise program (SHEP)” (44% lower risk), omega-3 fatty acids (47% lower risk), or both SHEP and omega-3s (61% lower risk)197Bischoff-Ferrari HA, Willett WC et al. Combined vitamin D, omega-3 fatty acids, and a simple home exercise program may reduce cancer risk among active adults aged 70 and older: a randomized clinical trial. Frontiers in Aging. 2022 Apr 25;3.
Good evidence of lower risk of metastatic or fatal cancer among people without cancer and not overweight or obese at baseline treated with vitamin D3
- Lower risk of metastatic or fatal cancer among people without cancer at baseline treated with vitamin D3, with effects mostly among people with body mass index (BMI) below 25 and no evidence of an effect among people with higher BMI 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 effects198Chandler PD, Chen WY et al. Effect of vitamin D3 supplements on development of advanced cancer: a secondary analysis of the VITAL randomized clinical trial. Journal of the American Medical Association Network Open. 2020 Nov 2;3(11):e2025850.
Good evidence of lower risk of recurrence among people with breast cancer with higher 25(OH)D levels at diagnosis
Good evidence of higher risk of breast cancer among people with low 25(OH)D levels, and especially among premenopausal women
Modest evidence of moderately lower risk of recurrence among people taking vitamin D supplements after a diagnosis of ER positive but not ER negative breast cancer
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 slightly lower risk of breast cancer among people with higher vitamin D intake
Vitamin D levels
Recurrence: good evidence of lower risk of recurrence among people with breast cancer with higher 25(OH)D levels at diagnosis
- Substantially lower risk of recurrence (better disease-free survivalthe time during and after successful treatment of a disease during which there are no signs and symptoms of the disease that was treated; this is the same as recurrence-free survival) among women with breast cancer with the highest 25(OH)D levels 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 12 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 studies199Li C, Li H, Zhong H, Li X. Association of 25-hydroxyvitamin D level with survival outcomes in female breast cancer patients: a meta-analysis. Journal of Steroid Biochemistry and Molecular Biology. 2021 Sep;212:105947.
- 58% lower risk of recurrence (better disease-free survival) among people with breast cancer with the highest 25(OH)D levels at diagnosis compared to the lowest in a meta-analysis of 4 studies200Li M, Chen P et al. Review: the impacts of circulating 25-hydroxyvitamin D levels on cancer patient outcomes: a systematic review and meta-analysis. Journal of Clinical Endocrinology and Metabolism. 2014 Jul;99(7):2327-36.
- 21% lower risk of recurrence and 18% lower risk of invasive disease recurrence across almost 10 years among people with breast cancer with 25(OH)D levels of 30 ng/ml or higher compared to less than 20 ng/ml at the time of diagnosis in a large observational study201Yao S, Sheng H et al. Clinically sufficient vitamin D levels at breast cancer diagnosis and survival outcomes in a prospective cohort of 3,995 patients after a median follow-up of 10 years. Poster presentation at the ASCO 2021 Annual Meeting. Viewed June 15, 2021.
Cancer diagnosis: good evidence of higher risk of breast cancer among people with low 25(OH)D levels, and especially among premenopausal women
- 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 lower risk of breast cancer among people with the highest 25(OH)D levels compared to the lowest in a large meta-analysis of 30 observational studies202Kim Y, Je Y. Vitamin D intake, blood 25(OH)D levels, and breast cancer risk or mortality: a meta-analysis. British Journal of Cancer. 2014 May 27;110(11):2772-84.
- Almost double the risk of breast cancer among women with 25(OH)D levels less than 10 ng/mL compared to higher levels in a meta-analysis of 22 observational studies203Hossain S, Beydoun MA et al. Vitamin D and breast cancer: a systematic review and meta-analysis of observational studies. Clinical Nutrition ESPEN. 2019 Apr;30:170-184.
- Lower risk of breast cancer among people with higher 25(OH)D levels compared to lower levels, especially among premenopausal women, in a meta-analysis of 68 observational studies204Estébanez N, Gómez-Acebo I, Palazuelos C, Llorca J, Dierssen-Sotos T. Vitamin D exposure and risk of breast cancer: a meta-analysis. Scientific Reports. 2018 Jun 13;8(1):9039.
- 6% lower risk of breast cancer with each 2 ng/mL (5 nmol/L) increase in blood vitamin D levels in a meta-analysis of 50 observational studies205Song D, Deng Y et al. Vitamin D intake, blood vitamin D levels, and the risk of breast cancer: a dose-response meta-analysis of observational studies. Aging (Albany NY). 2019 Dec 28;11(24):12708-12732.
- Higher risk of breast cancer among people with 25(OH)D levels below either 20 ng/mL or 30 ng/mL compared to higher levels in a meta-analysis of 25 observational studies206Voutsadakis IA. Vitamin D baseline levels at diagnosis of breast cancer: a systematic review and meta-analysis. Hematology/Oncology and Stem Cell Therapy. 2021 Mar;14(1):16-26.
- Substantially lower risk of breast cancer among premenopausal women with the highest 25(OH)D levels compared to the lowest, but no evidence of an effect among postmenopausal women in a mid-sized observational study207Jamshidinaeini Y, Akbari ME, Abdollahi M, Ajami M, Davoodi SH. Vitamin D status and risk of breast cancer in Iranian women: a case-control study. Journal of the American College of Nutrition. 2016 Sep-Oct;35(7):639-646.
- More than double the risk of breast cancer among women with 25(OH)D levels less than 20ng/mL compared to higher levels in a mid-sized observational study208Sofi NY, Jain M et al. Reproductive factors, nutritional status and serum 25(OH)D levels in women with breast cancer: a case control study. Journal of Steroid Biochemistry and Molecular Biology. 2018 Jan;175:200-204.
Vitamin D intake
Recurrence: modest evidence of moderately lower risk of recurrence among people taking vitamin D supplements after a diagnosis of ER positive but not ER negative breast cancer
- Moderately lower risk of recurrence among people taking vitamin D supplements after a diagnosis of ER positive but not ER negative breast cancer compared to no vitamin D in a large meta-analysis of 4 observational studies209Poole EM, Shu X et al. Postdiagnosis supplement use and breast cancer prognosis in the After Breast Cancer Pooling Project. Breast Cancer Research and Treatment. 2013 Jun;139(2):529-37.
Cancer diagnosis: preliminary evidence of slightly lower risk of breast cancer among people with higher vitamin D intake
- A weak trend toward slightly lower risk of breast cancer among people with the highest vitamin D intake compared to the lowest in a large meta-analysis of 30 observational studies210Kim Y, Je Y. Vitamin D intake, blood 25(OH)D levels, and breast cancer risk or mortality: a meta-analysis. British Journal of Cancer. 2014 May 27;110(11):2772-84.
- Slightly lower risk of breast cancer among women with each 100 IU vitamin D per day increase in intake, either from supplements alone or supplements and diet, in a meta-analysis of 22 observational studies211Hossain S, Beydoun MA et al. Vitamin D and breast cancer: a systematic review and meta-analysis of observational studies. Clinical Nutrition ESPEN. 2019 Apr;30:170-184.
- A weak trend toward lower risk in cohort studies but no evidence of an effect in case-control studies on risk of breast cancer with an increase of 400 IU vitamin D per day in a meta-analysis of 20 observational studies212Song D, Deng Y et al. Vitamin D intake, blood vitamin D levels, and the risk of breast cancer: a dose-response meta-analysis of observational studies. Aging (Albany NY). 2019 Dec 28;11(24):12708-12732.
Good evidence of lower risk of colorectal cancer incidence or mortality among people with higher 25(OH)D levels
Good evidence of lower risk of colorectal cancer among people with higher total vitamin D intake
Modest evidence of slightly lower risk of CRC as a whole with each increase of 100 IU dietary vitamin D intake
Good evidence of slightly lower risk of colorectal cancer among people taking vitamin D supplements
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. on risk of adenoma after colorectal adenoma surgery among people treated with vitamin D3 in a large study
Vitamin D levels: good evidence of lower risk of colorectal cancer incidence or mortality among people with higher 25(OH)D levels
- Substantially lower risk of colorectal cancer among people with higher 25(OH)D levels compared to lower levels, with higher effects among women compared to men, among people with higher intake of calcium, and among European and American populations compared to Asian populations, in a very 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 30 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 studies213Huang D, Lei S et al. Additively protective effects of vitamin D and calcium against colorectal adenoma incidence, malignant transformation and progression: a systematic review and meta-analysis. Clinical Nutrition. 2020 Aug;39(8):2525-2538.
- Moderately lower colorectal cancer-specific mortality among people without cancer at baseline with higher 25(OH)D levels compared to lower levels in a meta-analysis of 11 observational studies214Huang D, Lei S et al. Additively protective effects of vitamin D and calcium against colorectal adenoma incidence, malignant transformation and progression: a systematic review and meta-analysis. Clinical Nutrition. 2020 Aug;39(8):2525-2538.
- 31% higher risk of colorectal cancer among people with 25(OH)D levels less than 12 ng/mL (30 nmol/L) compared to levels between 20 and 25 ng/mL (50 and 62.5 nmol/L) in a large meta-analysis of 17 observational studies215McCullough ML, Zoltick ES et al. Circulating vitamin D and colorectal cancer risk: an international pooling project of 17 cohorts. JNCI: Journal of the National Cancer Institute. 2019 Feb 1;111(2):158-169.
- 19% lower risk of colorectal cancer among people with 25(OH)D levels between 75 and 87.5 nmol/L compared to levels between 30 and 35 ng/mL (75 and 87.5 nmol/L) compared to levels between 20 and 25 ng/mL (50 and 62.5 nmol/L), and 27% lower risk with levels between 35 and 40 ng/mL (87.5 and 100 nmol/L), but no further benefit at higher levels in a large meta-analysis of 17 observational studies216McCullough ML, Zoltick ES et al. Circulating vitamin D and colorectal cancer risk: an international pooling project of 17 cohorts. JNCI: Journal of the National Cancer Institute. 2019 Feb 1;111(2):158-169.
- Moderately lower risk of colorectal cancer among people with highest 25(OH)D levels compared to lowest in meta-analyses of 14,217Ekmekcioglu C, Haluza D, Kundi M. 25-hydroxyvitamin D status and risk for colorectal cancer and type 2 diabetes mellitus: a systematic review and meta-analysis of epidemiological studies. International Journal of Environmental Research and Public Health. 2017 Jan 28;14(2):127. 15,218Garland CF, Gorham ED. Dose-response of serum 25-hydroxyvitamin D in association with risk of colorectal cancer: a meta-analysis. Journal of Steroid Biochemistry and Molecular Biology. 2017 Apr;168:1-8. 9,219Ma Y, Zhang P et al. Association between vitamin D and risk of colorectal cancer: a systematic review of prospective studies. Journal of Clinical Oncology. 2011 Oct 1;29(28):3775-82. 8,220Zhang L, Zou H et al. Association between blood circulating vitamin D and colorectal cancer risk in Asian countries: a systematic review and dose-response meta-analysis. British Medical Journal Open. 2019 Dec 23;9(12):e030513. and 5221Touvier M, Chan DS et al. Meta-analyses of vitamin D intake, 25-hydroxyvitamin D status, vitamin D receptor polymorphisms, and colorectal cancer risk. Cancer Epidemiology, Biomarkers & Prevention. 2011 May;20(5):1003-16. observational studies
- Lower risk of colorectal cancer, with stronger effects for rectal cancer compared to colon cancer, among people with the highest 25(OH)D levels compared to lowest in a meta-analysis of 8 observational studies222Lee JE, Li H et al. Circulating levels of vitamin D and colon and rectal cancer: the Physicians’ Health Study and a meta-analysis of prospective studies. Cancer Prevention Research (Philadelphia). 2011 May;4(5):735-43.
- 20% lower risk of colorectal adenomas among people with higher 25(OH)D levels compared to lower levels in a meta-analysis of 22 observational studies223Huang D, Lei S et al. Additively protective effects of vitamin D and calcium against colorectal adenoma incidence, malignant transformation and progression: a systematic review and meta-analysis. Clinical Nutrition. 2020 Aug;39(8):2525-2538.
Vitamin D intake: good evidence of lower risk of colorectal cancer among people with higher total vitamin D intake
- Moderately lower risk of colorectal cancer among people with higher total vitamin D intake (16 studies) compared to lower intake, and slightly lower risk with higher dietary intake (34 studies), or supplement intake (16 studies) compared to lower intake in a very large meta-analysis of studies224Huang D, Lei S et al. Additively protective effects of vitamin D and calcium against colorectal adenoma incidence, malignant transformation and progression: a systematic review and meta-analysis. Clinical Nutrition. 2020 Aug;39(8):2525-2538.
- Lower risk of colorectal adenomas among people with higher total vitamin D intake compared to lower intake (10 studies), but not dietary intake alone (10 studies) nor supplement intake alone (5 studies) in a meta-analysis of studies225Huang D, Lei S et al. Additively protective effects of vitamin D and calcium against colorectal adenoma incidence, malignant transformation and progression: a systematic review and meta-analysis. Clinical Nutrition. 2020 Aug;39(8):2525-2538.
- 25% lower risk of colorectal cancer among people with the highest total vitamin D intake compared to the lowest in a meta-analysis of 5 meta-analyses of case-control observational studies mostly of good quality, but no evidence of an effect in a separate meta-analysis of prospective observational studies226Boughanem H, Canudas S et al. Vitamin D intake and the risk of colorectal cancer: an updated meta-analysis and systematic review of case-control and prospective cohort studies. Cancers (Basel). 2021 Jun 4;13(11):2814.
- Slightly lower risk of colorectal cancer among people with highest vitamin D intake compared to the lowest in a very large meta-analysis of observational studies227Ma Y, Zhang P et al. Association between vitamin D and risk of colorectal cancer: a systematic review of prospective studies. Journal of Clinical Oncology. 2011 Oct 1;29(28):3775-82.
Vitamin D from diet only: modest evidence of slightly lower risk of CRC as a whole with each increase of 100 IU dietary vitamin D intake
- Slightly lower risk of CRC as a whole with each increase of 100 IU dietary vitamin D intake per day (10 studies), but no significant effect among studies investigating only colon (8 studies) or rectal (6 studies) cancer separately in a meta-analysis of observational studies228Touvier M, Chan DS et al. Meta-analyses of vitamin D intake, 25-hydroxyvitamin D status, vitamin D receptor polymorphisms, and colorectal cancer risk. Cancer Epidemiology, Biomarkers & Prevention. 2011 May;20(5):1003-16.
Vitamin D from supplements only
Good evidence of slightly lower risk of colorectal cancer among people taking vitamin D supplements
- Slightly lower risk of colorectal cancer among people taking vitamin D supplements compared to no supplements in a very large meta-analysis of 21 observational studies229Xu Y, Qian M et al. The effect of vitamin D on the occurrence and development of colorectal cancer: a systematic review and meta-analysis. International Journal of Colorectal Disease. 2021 Jul;36(7):1329-1344.
- 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 lower risk of colorectal cancer among people taking vitamin D compared to no use (5 studies) but no evidence of an effect on risk of colorectal cancer among people taking higher levels of vitamin D compared to lower levels (4 studies), although a lower risk for each 100 mg increase in vitamin D per day (3 studies) in meta-analyses of observational studies230Heine-Bröring RC, Winkels RM et al. Dietary supplement use and colorectal cancer risk: a systematic review and meta-analyses of prospective cohort studies. International Journal of Cancer. 2015 May 15;136(10):2388-401.
No evidence of an effect on risk of adenoma after colorectal adenoma surgery among people treated with vitamin D3 in a large study
- No evidence of an effect on risk of adenoma after colorectal adenoma surgery among people age 45–75 years with vitamin D levels between 12 and 90 ng/ml treated with 1000 IU vitamin D3 per day compared to no vitamin D3 in a 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 effects231Calderwood AH, Baron JA et al. No evidence for posttreatment effects of vitamin D and calcium supplementation on risk of colorectal adenomas in a randomized trial. Cancer Prevention Research (Philadelphia, Pa.). 2019 May;12(5):295-304.
Colorectal cancer and pancreatic cancer are listed separately.
Good evidence of higher risk of liver cancer among people with low levels of vitamin D
Preliminary evidence of lower risk of recurrence after surgery among people with esophageal cancer taking vitamin D supplements
Vitamin D levels: good evidence of higher risk of liver cancer among people with low levels of vitamin D
- More than double the risk of liver cancer among people with vitamin D deficiency (undefined) compared to sufficiency (undefined) 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 11 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 studies232Yi Z, Wang L, Tu X. Effect of vitamin D deficiency on liver cancer risk: a systematic review and meta-analysis. Asian Pacific Journal of Cancer Prevention. 2021 Apr 1;22(4):991-997.
- 22% lower risk of liver cancer among people with highest 25(OH)D levels compared to the lowest, with an 8% lower risk with each 4 ng/mL (10 nmol/L) increase in 25(OH)D levels in a large meta-analysis of 6 observational studies233Guo XF, Zhao T, Han JM, Li S, Li D. Vitamin D and liver cancer risk: a meta-analysis of prospective studies. Asia Pacific Journal of Clinical Nutrition. 2020;29(1):175-182.
- 47% lower risk of liver cancer among people with the highest 25(OH)D levels compared to lowest in a meta-analysis of 6 observational studies234Zhang Y, Jiang X et al. Serum vitamin D levels and risk of liver cancer: a systematic review and dose-response meta-analysis of cohort studies. Nutrition and Cancer. 2021;73(8):1-9.
Vitamin D intake: preliminary evidence of lower risk of recurrence after surgery among people with esophageal cancer taking vitamin D supplements
- Lower risk of recurrence (better disease-free survival) at 24 months after surgery among people with esophageal cancer taking 200–400 IU vitamin D supplements daily compared to no supplements in a mid-sized observational study235Wang L, Wang C, Wang J, Huang X, Cheng Y. Longitudinal, observational study on associations between postoperative nutritional vitamin D supplementation and clinical outcomes in esophageal cancer patients undergoing esophagectomy. Scientific Reports. 2016 Dec 13;6:38962.
Ovarian cancer is listed separately.
Preliminary evidence of lower risk of recurrence among women with grade 2 or 3 cervical intraepithelial neoplasia treated with vitamin D
- Lower risk of recurrence of grade 1–3 disease among women with grade 2 or 3 cervical intraepithelial neoplasia treated with 50,000 IU vitamin D3 every 2 weeks for 6 months compared to placebo, with most of the effect relating to grade 1 disease in a small 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 effects236Vahedpoor Z, Mahmoodi S et al. Long-term vitamin D supplementation and the effects on recurrence and metabolic status of cervical intraepithelial neoplasia grade 2 or 3: a randomized, double-blind, placebo-controlled trial. Annals of Nutrition and Metabolism. 2018;72(2):151-160.
Good evidence of lower risk of head and neck cancer among people with high 25(OH)D levels
Good evidence of lower risk of head and neck cancer among people with high intake of vitamin D in their diet
Preliminary evidence of lower risk of recurrence among people with head and neck cancer with higher total (diet and supplement) intake of vitamin D
Vitamin D levels: good evidence of lower risk of head and neck cancer among people with high 25(OH)D levels
- Lower risk of head and neck cancer among people with high 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 16 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 studies237Pu Y, Zhu G et al. Association between vitamin D exposure and head and neck cancer: a systematic review with meta-analysis. Frontiers in Immunology. 2021 Feb 23;12:627226.
Vitamin D intake
Recurrence: preliminary evidence of lower risk of recurrence among people with head and neck cancer with higher total (diet and supplement) intake of vitamin D
- 53% lower risk of recurrence at 5 years among people with head and neck cancer with total (diet and supplement) intake of vitamin D of 675 IU per day or higher compared to less than 200 IU, but no evidence of effects for vitamin D from diet alone or from supplements alone, in a mid-sized observational study238Yokosawa EB, Arthur AE et al. Vitamin D intake and survival and recurrence in head and neck cancer patients. Laryngoscope. 2018 Nov;128(11):E371-E376.
Cancer risk: good evidence of lower risk of head and neck cancer among people with high intake of vitamin D in their diet
- Lower risk of head and neck cancer among people with high intake of vitamin D in their diet compared to “a regular diet” in a large meta-analysis of 16 observational studies239Pu Y, Zhu G et al. Association between vitamin D exposure and head and neck cancer: a systematic review with meta-analysis. Frontiers in Immunology. 2021 Feb 23;12:627226.
Modest evidence of lower risk of renal cell carcinoma among people, especially women, with the highest circulating vitamin D levels
Modest evidence of lower risk of renal cell carcinoma among people, especially women, with the highest dietary vitamin D intake
Vitamin D levels: modest evidence of lower risk of renal cell carcinoma among people, especially women, with the highest circulating vitamin D levels
- 24% lower risk of renal cell carcinoma among people, especially women, with the highest circulating vitamin D levels 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 4 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 studies240Wu J, Yang N, Yuan M. Dietary and circulating vitamin D and risk of renal cell carcinoma: a meta-analysis of observational studies. International Brazilian Journal of Urology. 2021 Jul-Aug;47(4):733-744.
Vitamin D intake: modest evidence of lower risk of renal cell carcinoma among people, especially women, with the highest dietary vitamin D intake
- 14% lower risk of renal cell carcinoma among people, especially women, with the highest dietary vitamin D intake compared to the lowest in a meta-analysis of 6 observational studies241Wu J, Yang N, Yuan M. Dietary and circulating vitamin D and risk of renal cell carcinoma: a meta-analysis of observational studies. International Brazilian Journal of Urology. 2021 Jul-Aug;47(4):733-744.
Good evidence of lower risk of lung cancer among people with higher 25(OH)D levels, although levels—above about 34 ng/mL—are linked to increased risk
Modest evidence of lower lung-cancer mortality among people without cancer at baseline with higher 25(OH)D levels
Modest evidence of slightly lower risk of lung cancer among people with the highest vitamin D intake from either diet or supplements
Vitamin D levels
Good evidence of lower risk of lung cancer among people with higher 25(OH)D levels, although very high levels—above about 85 nmol/L—are linked to increased risk
- A nonlinear effect, with a suggestion of higher risk of lung cancer among people with 25(OH)D levels either below about 18 ng/mL (45 nmol/L) or above about 34 ng/mL (85 nmol/L) compared to mid-range 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 12 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 studies242Wei H, Jing H, Wei Q, Wei G, Heng Z. Associations of the risk of lung cancer with serum 25-hydroxyvitamin D level and dietary vitamin D intake: a dose-response PRISMA meta-analysis. Medicine (Baltimore). 2018 Sep;97(37):e12282.
- Lower risk of lung cancer among people with higher 25(OH)D levels, with a trend toward lower risk between about 12 and 24 ng/mL (30 and 60 nmol/L) compared to the lower or higher levels, and an 8% lower risk with each 4 ng/mL (10 nmol/L) increase, in a meta-analysis of 9 observational studies243Feng Q, Zhang H, Dong Z, Zhou Y, Ma J. Circulating 25-hydroxyvitamin D and lung cancer risk and survival: a dose-response meta-analysis of prospective cohort studies. Medicine (Baltimore). 2017 Nov;96(45):e8613.
Modest evidence of lower lung-cancer mortality among people without cancer at baseline with higher 25(OH)D levels; see also indications that very high levels may increase mortality in Safety and precautions ›
- Lower risk of lung cancer-specific mortality among people without cancer at baseline with higher 25(OH)D levels compared to lower levels, and 7% lower risk with each 4 ng/mL (10 nmol/L) increase of 25(OH)D levels, in a meta-analysis of 4 observational studies244Feng Q, Zhang H, Dong Z, Zhou Y, Ma J. Circulating 25-hydroxyvitamin D and lung cancer risk and survival: a dose-response meta-analysis of prospective cohort studies. Medicine (Baltimore). 2017 Nov;96(45):e8613.
Vitamin D intake: modest evidence of slightly lower risk of lung cancer among people with the highest vitamin D intake from either diet or supplements
- Slightly lower risk of lung cancer among people with the highest dietary vitamin D intake compared to the lowest in a meta-analysis of 12 observational studies245Wei H, Jing H, Wei Q, Wei G, Heng Z. Associations of the risk of lung cancer with serum 25-hydroxyvitamin D level and dietary vitamin D intake: A dose-response PRISMA meta-analysis. Medicine (Baltimore). 2018 Sep;97(37):e12282.
- Slightly lower risk of lung cancer among people taking vitamin D supplements compared to non-users in a meta-analysis of 6 observational studies246Qian M, Lin J et al. The role of vitamin D intake on the prognosis and incidence of lung cancer: a systematic review and meta-analysis. Journal of Nutritional Science and Vitaminology (Tokyo). 2021;67(5):273-282.
Modest evidence of lower risk of recurrence among people with lymphoma with the highest 25(OH)D levels at diagnosis
No evidence of an effect of 25(OH)D levels on risk of non-Hodgkin lymphoma in a combined analysis of studies
Modest evidence of lower risk of non-Hodgkin lymphoma among people with high levels of exposure to sunlight/ultraviolet radiation
No evidence of an effect on risk of non-Hodgkin lymphoma among people with higher levels of dietary vitamin D intake in a combined analysis of 9 studies
Vitamin D levels
Modest evidence of lower risk of recurrence among people with lymphoma with the highest 25(OH)D levels at diagnosis
- 20% lower risk of recurrence (better disease-free survival) among people with lymphoma with the highest 25(OH)D levels at diagnosis compared to the lowest 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 2 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 studies247Li M, Chen P et al. Review: the impacts of circulating 25-hydroxyvitamin D levels on cancer patient outcomes: a systematic review and meta-analysis. Journal of Clinical Endocrinology and Metabolism. 2014 Jul;99(7):2327-36.
No evidence of an effect of 25(OH)D levels on risk of non-Hodgkin lymphoma in a combined analysis of studies
- No evidence of an effect on risk of non-Hodgkin lymphoma among people with 25(OH)D levels less than 20 ng/mL (50 nmol/L) compared to between 20 and 30 ng/mL (50 and 75 nmol/L) in a meta-analysis of 3 observational studies248Park HY, Hong YC, Lee K, Koh J. Vitamin D status and risk of non-Hodgkin lymphoma: an updated meta-analysis. PLoS One. 2019 Apr 29;14(4):e0216284.
Sunlight/ultraviolet radiation (UVR) exposure: modest evidence of lower risk of non-Hodgkin lymphoma among people with high levels of exposure to sunlight/ultraviolet radiation
- 20% lower risk of non-Hodgkin lymphoma among people with high levels of exposure to sunlight/UV radiation compared to low levels in a meta-analysis of 17 observational studies249Park HY, Hong YC, Lee K, Koh J. Vitamin D status and risk of non-Hodgkin lymphoma: an updated meta-analysis. PLoS One. 2019 Apr 29;14(4):e0216284.
Vitamin D intake: no evidence of an effect on risk of non-Hodgkin lymphoma among people with higher levels of dietary vitamin D intake in a combined analysis of 9 studies
- No evidence of an effect on risk of non-Hodgkin lymphoma among people with dietary vitamin D intake of 200 IU or more per day compared to less in a meta-analysis of 9 observational studies250Park HY, Hong YC, Lee K, Koh J. Vitamin D status and risk of non-Hodgkin lymphoma: an updated meta-analysis. PLoS One. 2019 Apr 29;14(4):e0216284.
Modest evidence of lower risk of melanoma recurrence among people with higher 25(OH)D levels
Modest evidence of a link between vitamin D deficiency and melanoma incidence/stage
Preliminary evidence of higher incidence of greater tumor size at diagnosis and metastasis recurrence among people with Merkel cell carcinoma with low vitamin D levels
Preliminary evidence of lower incidence of past or present melanoma or any type of skin cancer among people regularly using vitamin D supplements
Vitamin D levels
Recurrence: modest evidence of lower risk of melanoma recurrence among people with higher 25(OH)D levels
- Almost 5 times higher risk of recurrence (shorter disease-free survival) at 12 months among people with newly resected stage 2 melanoma with low 25(OH)D levels (below 20 ng/mL from December to July and below 30 ng/mL from August to November) and Breslow score of 3 mm or more compared to those with Breslow score less than 3 mm and/or high levels of 25(OH)D 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 effects251Johansson H, Spadola G et al. Vitamin D supplementation and disease-free survival in stage ii melanoma: a randomized placebo controlled trial. Nutrients. 2021 Jun 4;13(6):1931.
- Lower risk of recurrence (longer disease-free intervals) a year or more after diagnosis among people with resected stage 2 melanoma treated with bevacizumab with higher vitamin D levels compared to lower levels, but no evidence of an effect among people with stage 3 cancer or not treated with bevacizumab, in a mid-sized observational study252Lipplaa A, Fernandes R et al. 25-hydroxyvitamin D serum levels in patients with high risk resected melanoma treated in an adjuvant bevacizumab trial. British Journal of Cancer. 2018 Oct;119(7):793-800.
Cancer risk
Modest evidence of a link between vitamin D deficiency and melanoma incidence/stage; also see evidence of a higher risk of skin cancer among people with high levels of vitamin D in Safety and precautions ›
- Higher prevalence of vitamin D deficiency among people with melanoma compared to no melanoma, and higher vitamin D levels among people with Breslow thickness at or below 1 mm compared to higher thickness 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 25 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 studies253Tsai TY, Kuo CY, Huang YC. The association between serum vitamin D level and risk and prognosis of melanoma: a systematic review and meta-analysis. Journal of the European Academy of Dermatology and Venereology. 2020 Aug;34(8):1722-1729.
Preliminary evidence of higher incidence of greater tumor size at diagnosis and metastasis recurrence among people with Merkel cell carcinoma with low vitamin D levels
- Higher incidence of greater tumor size at diagnosis and metastasis recurrence among people with Merkel cell carcinoma with vitamin D levels below 20 ng/mL (50 nmol/L) within 3 years after diagnosis in a small observational study254Samimi M, Touzé A et al. Vitamin D deficiency is associated with greater tumor size and poorer outcome in Merkel cell carcinoma patients. Journal of the European Academy of Dermatology and Venereology. 2014 Mar;28(3):298-308.
Vitamin D intake: preliminary evidence of lower incidence of past or present melanoma or any type of skin cancer among people regularly using vitamin D supplements
- Lower incidence of past or present melanoma or any type of skin cancer, and no evidence of an effect on photoaging, actinic keratoses, nevi, basal, and squamous cell carcinoma, among people regularly using vitamin D supplements compared to non-users in a mid-sized observational study255Kanasuo E, Siiskonen H, Haimakainen S, Komulainen J, Harvima IT. Regular use of vitamin D supplement is associated with fewer melanoma cases compared to non-use: a cross-sectional study in 498 adult subjects at risk of skin cancers. Melanoma Research. 2023 Apr 1;33(2):126-135.
Modest evidence of slightly lower risk of ovarian cancer among people with higher circulating vitamin D levels
Weak evidence of a lower risk of ovarian cancer among people with higher dietary vitamin D intake
Insufficient evidence of lower risk of ovarian cancer among people with higher vitamin D intake from supplements
Vitamin D levels: modest evidence of slightly lower risk of ovarian cancer among people with higher circulating vitamin D levels
- Slightly lower risk of ovarian cancer among people with circulating vitamin D levels of about 16 ng/mL (40 nmol/L) or higher compared to about 8 ng/mL (20 nmol/L) 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 4 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 studies256Liao MQ, Gao XP et al. Effects of dairy products, calcium and vitamin D on ovarian cancer risk: a meta-analysis of twenty-nine epidemiological studies. British Journal of Nutrition. 2020 Nov 28;124(10):1001-1012.
Vitamin D intake
Weak evidence of a lower risk of ovarian cancer among people with higher dietary vitamin D intake
Insufficient evidence of slightly lower risk of ovarian cancer among people with higher vitamin D intake from supplements
- 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 a lower risk of ovarian cancer among people with higher dietary vitamin D intake, but no evidence of an effect from supplement intake, whether with or without calcium, in a very large meta-analysis of 21 observational studies257Xu J, Chen K et al. Association between vitamin D/calcium intake and 25-hydroxyvitamin D and risk of ovarian cancer: a dose-response relationship meta-analysis. European Journal of Clinical Nutrition. 2021 Mar;75(3):417-429.
- Slightly lower risk of ovarian cancer among women with higher dietary vitamin D intake compared to lower levels, especially lower than about 200 IU per day, in a meta-analysis of 4 observational studies258Liao MQ, Gao XP et al. Effects of dairy products, calcium and vitamin D on ovarian cancer risk: a meta-analysis of twenty-nine epidemiological studies. British Journal of Nutrition. 2020 Nov 28;124(10):1001-1012.
No evidence of an effect on risk of pancreatic cancer among people with higher 25(OH)D levels in a combined analysis of studies
Insufficient (conflicting) evidencepreclinical evidence only OR clinical studies with such poor or unclear methodology that no conclusion can be drawn OR conflicting findings across clinical studies with no preponderance of evidence in one direction; conflicting evidence occurs when studies find conflicting effects (positive effect vs no effect or negative effect) with the same treatment and the same general study population (same cancer type, for example) (this is the CancerChoices definition; other researchers and studies may define this differently) of an effect of vitamin D intake on risk of pancreatic cancer
Vitamin D levels: no evidence of an effect on risk of pancreatic cancer among people with higher 25(OH)D levels in a combined analysis of studies
- No evidence of an effect on risk of pancreatic cancer among people with higher 25(OH)D levels compared to lower 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 5 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 studies259Zhang X, Huang XZ et al. Plasma 25-hydroxyvitamin D levels, vitamin D intake, and pancreatic cancer risk or mortality: a meta-analysis. Oncotarget. 2017 Jun 29;8(38):64395-64406.
Vitamin D intake: insufficient (conflicting) evidence of an effect of vitamin D intake on risk of pancreatic cancer
- 25% lower risk of pancreatic cancer among people with the highest vitamin D intake levels compared to the lowest in a meta-analysis of 3 prospective observational studies;260Liu 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. also see evidence of higher risk in Safety and precautions ›
- No evidence of an effect on risk of pancreatic cancer among people with higher vitamin D intake compared to lower levels in a meta-analysis of 2 observational studies261Zhang X, Huang XZ et al. Plasma 25-hydroxyvitamin D levels, vitamin D intake, and pancreatic cancer risk or mortality: a meta-analysis. Oncotarget. 2017 Jun 29;8(38):64395-64406.
Good evidence of higher risk of prostate cancer among men with low 25(OH)D levels
Modest evidence of lower risk of aggressive prostate cancer among African-Americans or people with low body mass index taking the highest levels of vitamin D supplements, but not among other people
No evidence of an effect at 3 months on free or total PSA among healthy men taking vitamin D in a small study
Vitamin D levels: good evidence of higher risk of prostate cancer among men with low 25(OH)D levels
- Lower risk of prostate cancer among men with 25(OH)D levels higher than 15 ng/mL (37 nmol/L) compared to lower levels in an observationala type of analysis 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 an analysis 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 analysis within a very large study262Kristal 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.
- Higher risk of prostate cancer among men younger than age 51, but not older men, with 25(OH)D levels below 20 ng/mL (50 nmol/L) compared to higher levels, and higher risk of aggressive prostate cancer among those with the lowest levels in a very large observational study263Tuohimaa P, Lyakhovich A et al. Vitamin D and prostate cancer. Journal of Steroid Biochemistry and Molecular Biology. 2001 Jan-Mar;76(1-5):125-34.
- 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 prostate cancer among people with 25(OH)D levels less than 16 ng/mL (40 nmol/L) compared to 16-24 ng/mL (40–59 nmol/L) in a large observational study264Tuohimaa P, Tenkanen L et al. Both high and low levels of blood vitamin D are associated with a higher prostate cancer risk: a longitudinal, nested case-control study in the Nordic countries. International Journal of Cancer. 2004 Jan 1;108(1):104-8.
Vitamin D intake
Modest evidence of lower risk of aggressive prostate cancer among African-Americans or people with low body mass index taking the highest levels of vitamin D supplements, but not among other people
- 62% lower risk of aggressive prostate cancer among people taking the highest levels of vitamin D supplements compared to the lowest levels, but only among African-Americans and not European-Americans, or among men with low body mass index but not with higher body mass index, in a large observational study265Batai K, Murphy AB et al. Race and BMI modify associations of calcium and vitamin D intake with prostate cancer. BMC Cancer. 2017 Jan 19;17(1):64.
No evidence of an effect at 3 months on free or total PSA among healthy men taking vitamin D in a small study
- No evidence of an effect at 3 months on free or total PSA among healthy men of African-American descent taking 1000, 2000, or 4000 IU vitamin D compared to placebo 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 effects266Chandler PD, Giovannucci EL et al. Null association between vitamin D and PSA levels among black men in a vitamin D supplementation trial. Cancer Epidemiology, Biomarkers & Prevention. 2014 Sep;23(9):1944-7.
Good evidence of higher risk of thyroid cancer among people with low levels of vitamin D
- 30% higher risk of thyroid cancer among people with vitamin D deficiency (variously defined across studies) compared to sufficiency 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 6 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 of high quality267Zhao J, Wang H et al. Vitamin D deficiency as a risk factor for thyroid cancer: a meta-analysis of case-control studies. Nutrition. 2019 Jan;57:5-11.
- Lower 25(OH)D levels among people with thyroid cancer compared to controls in a meta-analysis of 12 observational studies of high quality268Zhao J, Wang H et al. Vitamin D deficiency as a risk factor for thyroid cancer: a meta-analysis of case-control studies. Nutrition. 2019 Jan;57:5-11.
- Higher risk of papillary thyroid cancer among people with the lowest levels of vitamin D compared to the highest, or with vitamin D deficiency (variously defined across studies) compared to sufficiency in a meta-analysis of 11 observational studies269Hu MJ, Zhang Q et al. Association between vitamin D deficiency and risk of thyroid cancer: a case-control study and a meta-analysis. Journal of Endocrinological Investigation. 2018 Oct;41(10):1199-1210.
No evidence of an effect on risk of conventional adenomas and serrated polyps among people treated with vitamin D and fish oil in a very large study
Good evidence of lower risk of cancer as a whole among postmenopausal women treated with vitamin D and calcium
Good evidence of lower risk of blood cancer among people treated with calcium and vitamin D supplements
Modest evidence of lower risk of breast cancer mortality but no evidence of an effect on risk of invasive breast cancer among postmenopausal women treated with calcium plus vitamin D, but see also an increased in risks among women with higher baseline intake of vitamin D in Safety and precautions ›
Weak evidence of a lower risk of colorectal cancer among women not treated with estrogen, but no evidence of an effect on risk across all women treated with vitamin D and calcium
Modest evidence of a slightly lower risk of colorectal adenoma recurrence, including advanced adenomas, among people treated with calcium and with higher 25(OH)D levels
Modest evidence of lower risk of invasive cutaneous squamous cell carcinoma among people with colorectal adenomas treated with vitamin D and calcium
Good evidence of lower risk of melanoma among postmenopausal women aged 50-79 with a history of non-melanoma skin cancer treated with vitamin D and calcium
No evidence of an effect on risk of melanoma among postmenopausal women aged 50-79 without a history of non-melanoma skin cancer treated with vitamin D and calcium
Modest evidence of lower risk of cancer among healthy community-dwelling adults aged 70 years or older treated with vitamin D in combination with strength exercise, omega-3 fatty acids, or both
Vitamin D and omega-3 fatty acids: no evidence of an effect on risk of conventional adenomas and serrated polyps among people treated with vitamin D and fish oil
- No evidence of an effect on risk of conventional adenomas and serrated polyps 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, treated with 2000 IU vitamin D3 and 1 g marine n-3 fatty acid per day compared with placebo, with a very 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 lower risk among people with serum 25(OH)D levels below 30 ng/mL compared to higher levels, 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 effects270Song 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.
Vitamin D and calcium
Cancer as a whole: good evidence of lower risk of cancer as a whole among postmenopausal women treated with vitamin D and calcium
- Lower risk of cancer as a whole at 1 year and a weak trend toward lower risk at 4 years among healthy postmenopausal women in rural counties and aged 55 years or older treated with 2000 IU vitamin D3 and 1500 mg calcium per day compared to placebos in a very large RCT271Lappe J, Watson P et al. Effect of vitamin D and calcium supplementation on cancer incidence in older women: a randomized clinical trial. Journal of the American Medical Association. 2017 Mar 28;317(12):1234-1243.
Blood cancer: good evidence of lower risk of blood cancer (hematologic malignancy) among people treated with calcium and vitamin D supplements
- 20% lower risk of hematologic malignancy (HM) but no evidence of an effect on HM mortality over 10 years among people without HM at baseline treated with calcium and vitamin D supplements compared to no supplements, with lower risks related to lymphoid malignancies, in a very large RCT272Ammann EM, Drake MT et al. Incidence of hematologic malignancy and cause-specific mortality in the Women’s Health Initiative randomized controlled trial of calcium and vitamin D supplementation. Cancer. 2017 Nov 1;123(21):4168-4177.
Breast cancer: modest evidence of lower risk of breast cancer mortality but no evidence of an effect on risk of invasive breast cancer among postmenopausal women treated with calcium plus vitamin D, but see also an increase in risk among women with higher baseline intake of vitamin D in Safety and precautions ›
- 7% lower risk of breast cancer 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;273Thomson 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 higher risk of cardiovascular disease mortality with use of calcium and vitamin D in Safety and precautions ›
- No evidence of an effect on risk of invasive breast cancer overall among postmenopausal women treated with calcium plus vitamin D compared to placebo in a very large RCT274Cauley 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.
Colorectal cancer
Modest evidence of a slightly lower risk of colorectal adenoma recurrence, including advanced adenomas, among people treated with calcium and with higher 25(OH)D levels
- Slightly lower risk of colorectal adenoma recurrence, including advanced adenomas, with each 12 ng/mL increase of 25(OH)D levels among people treated with 3 g calcium carbonate, but no evidence of an effect among people treated with placebo in a large RCT275Grau MV, Baron JA et al. Vitamin D, calcium supplementation, and colorectal adenomas: results of a randomized trial. JNCI: Journal of the National Cancer Institute. 2003;95(23):1765-1771.
Weak evidence of a lower risk of colorectal cancer among women not treated with estrogen, but no evidence of an effect on risk across all women treated with vitamin D and calcium; see also information about an increased risk among women treated with estrogen therapy treated with vitamin D and calcium in Safety and
precautions ›
- No evidence of an effect on risk of colorectal cancer among postmenopausal women treated with calcium plus vitamin D compared to placebo in a very large RCT276Cauley 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.
- A weak trend toward a lower risk of colorectal cancer among women not treated with estrogen therapy treated with 400 IU of vitamin-D3 plus 1000 mg elemental calcium compared to placebo in a secondary analysis of a very large RCT277Ding 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.
Skin cancer
Modest evidence of lower risk of invasive cutaneous squamous cell carcinoma among people with colorectal adenomas treated with vitamin D and calcium
- Lower risk of invasive cutaneous squamous cell carcinoma but not basal cell carcinoma at 8 years among people with colorectal adenomas treated with 1000 IU vitamin D3 and 1200 mg calcium carbonate per day for 3 or 5 years, but not vitamin D alone, compared to placebo in in a secondary analysis of a large RCT278Passarelli MN, Karagas MR et al. Risk of keratinocyte carcinomas with vitamin D and calcium supplementation: a secondary analysis of a randomized clinical trial. American Journal of Clinical Nutrition. 2020 Dec 10;112(6):1532-1539
Good evidence of lower risk of melanoma among postmenopausal women aged 50-79 with a history of non-melanoma skin cancer treated with vitamin D and calcium
No evidence of an effect on risk of melanoma among postmenopausal women aged 50-79 without a history of non-melanoma skin cancer treated with vitamin D and calcium
- Lower risk of melanoma but no evidence of an effect on non-melanoma skin cancer at about 7 years among postmenopausal women aged 50-79 with a history of non-melanoma skin cancer treated with 1,000 mg elemental calcium plus 400 IU vitamin D3 daily compared to placebo, but no evidence of an effect among women without a history of non-melanoma skin cancer, in a subgroup analysis within a very large RCT279Tang JY, Fu T et al. Calcium plus vitamin D supplementation and the risk of nonmelanoma and melanoma skin cancer: post hoc analyses of the women’s health initiative randomized controlled trial. Journal of Clinical Oncology. 2011 Aug 1;29(22):3078-84.
Vitamin D, strength exercise, and omega-3 fatty acids: modest evidence of lower risk of cancer among healthy community-dwelling adults aged 70 years or older treated with vitamin D in combination with strength exercise, omega-3 fatty acids, or both
- Lower risk of cancer as a whole among healthy community-dwelling adults aged 70 years or older taking 2000 IU supplemental vitamin D3 per day combined with “a simple home strength exercise program (SHEP)” (44% lower risk), omega-3 fatty acids (47% lower risk), or both SHEP and omega-3s (61% lower risk) compared to placebo in a large RCT280Bischoff-Ferrari HA, Willett WC et al. Combined vitamin D, omega-3 fatty acids, and a simple home exercise program may reduce cancer risk among active adults aged 70 and older: a randomized clinical trial. Frontiers in Aging. 2022 Apr 25;3:852643.
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Authors
Ms. Hepp is a researcher and communicator who has been writing and editing educational content on varied health topics for more than 20 years. She serves as lead researcher and writer for CancerChoices and also served as the first program manager. Her graduate work in research and cognitive psychology, her master’s degree in instructional design, and her certificate in web design have all guided her in writing and presenting information for a wide variety of audiences and uses. Nancy’s service as faculty development coordinator in the Department of Family Medicine at Wright State University also provided experience in medical research, plus insights into medical education and medical care from the professional’s perspective.
Dr. Ryan served as a research associate for CancerChoices. She is a licensed and board certified naturopathic physician and acupuncturist in Oregon. Dr. Ryan is the founder of Gentle Natural Wellness, a clinic specializing in bridging classical Chinese medicine with naturopathic medicine to provide individualized, compassionate care for people in the community. A Doctorate of Naturopathic Medicine and Master of Science in Oriental Medicine with honors from the National University of Natural Medicine, research in medical anthropology at the University of Hawai’i and George Mason University, language and culture programs at Obirin University (Tokyo) and Sogang University (Seoul), and studies of Chinese herbal medicine and qigong in China have provided a diverse background that has helped form a foundation for her community health and healing path.
Reviewer
Laura Pole is senior clinical consultant for CancerChoices. Laura is an oncology clinical nurse specialist who has been providing integrative oncology clinical care, navigation, consultation, and education services for over 40 years. She is the co-creator and co-coordinator of the Integrative Oncology Navigation Training at Smith Center for Healing and the Arts in Washington, DC. Laura also manages the “Media Watch Cancer News That You Can Use” listserv for Smith Center/Commonweal. In her role as a palliative care educator and consultant, Laura has served as statewide Respecting Choices Faculty for the Virginia POST (Physician Orders for Scope of Treatment) Collaborative as well as provided statewide professional education on palliative and end-of-life care for the Virginia Association for Hospices and Palliative Care.
For CancerChoices, Laura curates content and research, networks with clinical and organizational partners, brings awareness and education of integrative oncology at professional and patient conferences and programs, and translates research into information relevant to the patient experience as well as clinical practice.
Laura sees her work with CancerChoices as a perfect alignment of all her passions, knowledge and skills in integrative oncology care. She is honored to serve you.
Last update: May 30, 2024
Last full literature review: February 2022
CancerChoices provides information about integrative in cancer care, a patient-centered approach combining the best of conventional care, self care and evidence-informed complementary care in an integrated plan cancer care. We review complementaryin cancer care, complementary care involves the use of therapies intended to enhance or add to standard conventional treatments; examples include supplements, mind-body approaches such as yoga or psychosocial therapy, and acupuncture therapies and self-care lifestyle actions and behaviors that may impact cancer outcomes; examples include eating health-promoting foods, limiting alcohol, increasing physical activity, and managing stress practices to help patients and professionals explore and integrate the best combination of conventionalthe cancer care offered by conventionally trained physicians and most hospitals; examples are chemotherapy, surgery, and radiotherapy and complementary therapies and practices for each person.
Our staff have no financial conflicts of interest to declare. We receive no funds from any manufacturers or retailers gaining financial profit by promoting or discouraging therapies mentioned on this site.
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