Vitamin D

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 ›

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

• 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 studies²⁰⁶Tao 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(OH)D levels treated with high-dose vitamin D 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 vitamin D 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 design²⁰⁷Sheean 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 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 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 660 mg 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 effects²⁰⁸Haidari 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 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

• 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 RCT²⁰⁹Inglis 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 design²¹⁰Van 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.

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? ›

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 less loss of bone mineral density during hormone therapy among people treated with high amounts of vitamin D

• Less loss of bone mineral density during androgen deprivation therapy among people with prostate cancer treated with 50,000 IU vitamin D per week for 24 weeks compared to placebo, especially among people with low baseline serum 25-hydroxyvitamin D levels 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 effects²¹¹Peppone LJ, Kleckner AS et al. High-dose vitamin D to attenuate bone loss in patients with prostate cancer on androgen deprivation therapy: a phase 2 RCT. Cancer. 2024 Jul 15;130(14):2538-2551.
• 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 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 RCT²¹²Rastelli 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 RCT²¹³Peppone 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 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 lower markers of cardiotoxicity after adjuvanttreatment applied after initial treatment for cancer, especially to suppress secondary tumor formation chemotherapy among women newly diagnosed with breast cancer treated with vitamin D

• Lower markers of cardiotoxicity (lactate dehydrogenase and cardiac troponin T) after adjuvant doxorubicin-based chemotherapy among women newly diagnosed with breast cancer treated with 0.5 µg of oral vitamin D once a day throughout chemotherapy compared to chemotherapy 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 effects²¹⁴El-Bassiouny NA, Helmy MW, Hassan MAE, Khedr GA. The cardioprotective effect of vitamin D in breast cancer patients receiving adjuvant doxorubicin based chemotherapy. Clinical Breast Cancer. 2022 Jun;22(4):359-366.

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 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 effects²¹⁵Helde 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

• Higher incidence of grade 3 or higher chemotherapy-induced peripheral neuropathy during paclitaxel treatment among people with vitamin D insufficiency (less than 20 ng/mL) compared to sufficiency (20 ng/mL or higher) 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 study²¹⁶Chen CS, Zirpoli G et al. Vitamin D insufficiency as a risk factor for paclitaxel-induced peripheral neuropathy in SWOG S0221. Journal of the National Comprehensive Cancer Network. 2023 Nov;21(11):1172-1180.e3.
• 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 observational studies analyzed in a review²¹⁷Tofthagen 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 effects²¹⁸Bakr 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.

General cancer pain: 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 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 effects²¹⁹Helde 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 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 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 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 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 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 effects²²⁰Khan 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 RCT²²¹Rastelli 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.
• 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 study²²²Prieto-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.
• 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 RCT²²³Khan 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.
• 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 trial²²⁴Van 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 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

• 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 (50 nmol/L) or lower treated with an intramuscular injection of 300,000 IU vitamin D before surgery compared to no treatment in a small RCT²²⁵Hajimohammadebrahim-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.

Preliminary evidence of less pain after colorectal cancer surgery among people with sufficient vitamin D levels

• 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 50 nmol/L or higher) compared to deficient levels (less than 20 ng/mL) in a mid-sized observational study²²⁶Xia J, Li D 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.

Modest evidencesignificant effects in at least three small but well-designed randomized controlled trials (RCTs), or one or more well-designed, mid-sized clinical studies of reasonably good quality (RCTs or observational studies), or several small studies aggregated into a meta-analysis (this is the CancerChoices definition; other researchers and studies may define this differently) of higher 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 study²²⁷Andersen 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 study²²⁸Andersen 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 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 less frailty but no evidence of an effect on other measures of physical function during androgen deprivation therapy among people with prostate cancer treated with high-dose vitamin D

• A marker of less frailty (phase angle values) but no evidence of an effect on other measures of physical function (handgrip strength, standing balance, walking speed, chair stand, and such) during androgen deprivation therapy among people with prostate cancer treated with high-dose vitamin D (600 IU per day plus 50,000 IU per week) for 24 weeks compared to low-dose (600 IU/day plus weekly 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 effects²²⁹Inglis 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.

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 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 effects²³⁰Keshavarzi 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 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 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 study²³¹Ghorbanzadeh-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.

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 lower mortality but no evidence of an effect on incidence of graft-versus-host disease or veno-occlusive disease after stem cell transplant among pediatric patients with either malignant or nonmalignant diseases with higher vitamin D levels

• Lower mortality but no evidence of an effect on incidence of graft-versus-host disease or veno-occlusive disease after autologous and allogeneic hematopoietic stem cell transplant among pediatric patients with both malignant and nonmalignant diseases with higher vitamin D levels either before or after transplant 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 study²³²Bhandari R, Malvar J et al. Association between vitamin D and risk for early and late post-transplant complications. Biology of Blood and Marrow Transplantation. 2020 Feb;26(2):343-350.

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 effects²³³Witham 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 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 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 study²³⁴Ghahremani 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 RCTs²³⁵Cheng 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 RCTs²³⁶Vellekkatt 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 RCTs²³⁷Shaffer 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 RCT²³⁸Nowak 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 RCT²³⁹Witham 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 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 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 RCT²⁴⁰Karonova 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 RCT²⁴¹Wu 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.

Modest evidence of higher average joint pain scores among postmenopausal women with the lowest 25(OH)D levels

• Higher average joint pain scores among postmenopausal women with the lowest 25(OH)D levels compared to higher levels in a large observational study²⁴²Chlebowski RT, Johnson KC et al. 25-hydroxyvitamin D concentration, vitamin D intake and joint symptoms in postmenopausal women. Maturitas. 2011 Jan;68(1):73-8.

Reproductive side effects: good evidence of higher ovulation rates and pregnancy rates among people with polycystic ovary syndrome treated with vitamin D

• Higher ovulation rates (9 studies) and pregnancy rates (18 studies) among people with polycystic ovary syndrome treated with vitamin D compared to controls in meta-analyses of RCTs²⁴³Yang M, Shen X et al. Effects of vitamin D supplementation on ovulation and pregnancy in women with polycystic ovary syndrome: a systematic review and meta-analysis. Frontiers in Endocrinology (Lausanne). 2023 Aug 1;14:1148556.

Length of hospital stay: preliminary evidence of shorter ICU and hospital stays among people with benign brain tumors and low serum vitamin D levels treated with an intramuscular injection of high-dose vitamin D3 before surgery

• Shorter ICU and hospital stays among people with benign brain tumors and serum 25(OH)D levels of 20 ng/mL or less treated with an intramuscular injection of 300,000 IU vitamin D3 prior to surgery compared to surgery alone in a small RCT²⁴⁴Hajimohammadebrahim-Ketabforoush M, Shahmohammadi M, Keikhaee M, Eslamian G, Vahdat Shariatpanahi Z. Single high-dose vitamin D3 injection and clinical outcomes in brain tumor resection: a randomized, controlled clinical trial. Clinical Nutrition ESPEN. 2021 Feb;41:153-159.

Vitamin D and calcium

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 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 cancer²⁴⁵Datta 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 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 effects²⁴⁶Orgel 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 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 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

People treated with hormonal therapy for prostate cancer, such as in this study, are at great risk for bone loss, osteoporosis, and bone fractures.²⁴⁷Suarez-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.

• 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 RCT²⁴⁸Khriguian 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.

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 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 RCT²⁴⁹Cauley 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.

Exercise, whey protein, calcium, and 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 preserved femoral neck bone density and better total body lean mass, leg muscle strength, and dynamic mobility during androgen deprivation therapy among men treated with weekly progressive resistance training plus weight-bearing impact exercise 3 times a week with daily supplementation of whey protein, calcium, and vitamin D

• Preserved femoral neck bone density and better total body lean mass, leg muscle strength, and dynamic mobility during androgen deprivation therapy among men treated with weekly progressive resistance training plus weight-bearing impact exercise 3 times a week with daily supplementation of whey protein, calcium, and vitamin D compared to usual care in a small RCT²⁵⁰Dalla Via J, Owen PJ et al. Musculoskeletal responses to exercise plus nutrition in men with prostate cancer on androgen deprivation: a 12-month RCT. Medicine and Science in Sports and Exercise. 2021 Oct 1;53(10):2054-2065.

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 RCT²⁵¹Solmaz 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.

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 study²⁵²Mouchel 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 RCT²⁵³Okereke 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 RCT²⁵⁴Brown 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.

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 RCT²⁵⁵Chous 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 RCT²⁵⁶Valensi 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.

Vitamin D and metformin: 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 a lower marker of insulin resistance (HOMA-IR), lower body weight and testosterone, and more regular menstrual cycles among people with polycystic ovary syndrome treated with metformin and vitamin D

• A lower marker of insulin resistance (HOMA-IR), lower body weight and testosterone, and more regular menstrual cycles among people with polycystic ovarian syndrome treated with metformin and vitamin D compared to controls in a meta-analysis of 9 RCTs²⁵⁷Xiang L, Liao M, Su Y. Efficacy of metformin combined with vitamin D in the treatment of polycystic ovarian syndrome: a meta-analysis. African Journal of Reproductive Health. 2024 Feb 28;28(2):43-54.

Also see evidence of higher risk of cancer mortality among men with the levels of vitamin D above 40 ng/mL (100 nmol/L) in Safety and precautions ›

Vitamin 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 higher risk of cancer among people with low 25(OH)D levels

• 20% lower risk of cancer as a whole among people with high vitamin D blood levels compared to low levels in 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 18 meta-analyses including both 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 and 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 studies²⁵⁸Arayici ME, Basbinar Y, Ellidokuz H. Vitamin D intake, serum 25-hydroxyvitamin-D (25(OH)D) levels, and cancer risk: a comprehensive meta-meta-analysis including meta-analyses of randomized controlled trials and observational epidemiological studies. Nutrients. 2023 Jun 12;15(12):2722.

Good but somewhat conflicting evidence of lower cancer mortality among people without cancer at baseline with higher 25(OH)D levels

• 26% lower risk of cancer mortality among people with high vitamin D blood levels compared to low levels in meta-analyses of 8 meta-analyses including both RCTs and observational studies²⁵⁹Arayici ME, Basbinar Y, Ellidokuz H. Vitamin D intake, serum 25-hydroxyvitamin-D (25(OH)D) levels, and cancer risk: a comprehensive meta-meta-analysis including meta-analyses of randomized controlled trials and observational epidemiological studies. Nutrients. 2023 Jun 12;15(12):2722.
• No evidence of an effect on cancer-specific mortality among people without cancer at baseline with the lowest 25-hydroxyvitamin D levels compared to the highest in a large meta-analysis of 8 observational studies²⁶⁰Schöttker B, Jorde R et al; Consortium on Health and Ageing: Network of Cohorts in Europe and the United States. Vitamin D and mortality: meta-analysis of individual participant data from a large consortium of cohort studies from Europe and the United States. BMJ. 2014 Jun 17;348:g3656.

Vitamin D intake

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

• 11% lower cancer mortality among people without cancer at baseline with high vitamin D intake compared to low intake in meta-analyses of 7 meta-analyses of RCTs²⁶¹Arayici ME, Basbinar Y, Ellidokuz H. Vitamin D intake, serum 25-hydroxyvitamin-D (25(OH)D) levels, and cancer risk: a comprehensive meta-meta-analysis including meta-analyses of randomized controlled trials and observational epidemiological studies. Nutrients. 2023 Jun 12;15(12):2722.
• 24% lower risk of cancer as a whole among normal-weight people treated with a daily vitamin D supplement compared to controls (2 studies) but no evidence of an effect on risk among overweight or obese people (3 studies) in meta-analyses of RCTs²⁶²Keum N, Chen QY, Lee DH, Manson JE, Giovannucci E. Vitamin D supplementation and total cancer incidence and mortality by daily vs. infrequent large-bolus dosing strategies: a meta-analysis of randomised controlled trials. British Journal of Cancer. 2022 Sep;127(5):872-878.
• 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 effects²⁶³Zhang Y, 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 among people without cancer at baseline taking supplements and attaining 25(OH)D levels of 22-54 ng/mL (54–135  nmol/L) compared to controls not taking supplements, with effects from daily dosing but not from infrequent bolus dosing in a meta-analysis of 5 RCTs²⁶⁴Keum 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.
• Lower cancer mortality during more than 12 years among people aged 50-75 years with low vitamin D levels (deficiency or insufficiency) treated with vitamin D, but no evidence of an effect among people with sufficient vitamin D levels (20 ng/mL or 50 nmol/L) treated with vitamin D in a large observational study²⁶⁵Brenner H, Jansen L, Saum KU, Holleczek B, Schöttker B. Vitamin D supplementation trials aimed at reducing mortality have much higher power when focusing on people with low serum 25-hydroxyvitamin D concentrations. Journal of Nutrition. 2017 Jul;147(7):1325-1333.
• Slightly lower cancer mortality but no evidence of an effect on cancer risk among people without cancer at baseline treated with vitamin D3 compared to controls in a large meta-analysis of 56 RCTs²⁶⁶Bjelakovic G, Gluud LL et al. Vitamin D supplementation for prevention of mortality in adults. Cochrane Database of Systematic Reviews. 2014 Jan 10;(1):CD007470.

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 cancer as a whole among people with high vitamin D intake

• No evidence of an effect on risk of cancer as a whole among people with high vitamin D intake compared to low intake in a meta-analysis of 8 meta-analyses of RCTs²⁶⁷Arayici ME, Basbinar Y, Ellidokuz H. Vitamin D intake, serum 25-hydroxyvitamin-D (25(OH)D) levels, and cancer risk: a comprehensive meta-meta-analysis including meta-analyses of randomized controlled trials and observational epidemiological studies. Nutrients. 2023 Jun 12;15(12):2722.
• No evidence of an effect on cancer incidence among people without cancer at baseline taking supplements and attaining 25(OH)D levels of 22-54 ng/mL (55–135 nmol/L) compared to controls not taking supplements in a meta-analysis of 10 RCTs²⁶⁸Keum 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.

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

• 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 RCT²⁶⁹Bischoff-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 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 risk of metastatic or fatal cancer among people without cancer and not overweight or obese at baseline treated with vitamin D

• 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 effects²⁷⁰Chandler 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.

Vitamin 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 risk of bladder cancer among people with higher vitamin D levels

• Lower risk of bladder cancer among people with serum 25-hydroxyvitamin D levels above 30 ng/mL (75 nmol/L) 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 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 studies²⁷¹Zhao Y, Chen C et al. Comparative efficacy of vitamin D status in reducing the risk of bladder cancer: a systematic review and network meta-analysis. Nutrition. 2016 May;32(5):515-23.
• 32% higher risk of bladder cancer among people with the lowest serum levels of vitamin D compared to the highest levels in a large meta-analysis of 5 observational studies²⁷²Zhang H, Zhang H et al. Vitamin D deficiency and increased risk of bladder carcinoma: a meta-analysis. Cell Physiology and Biochemistry. 2015;37(5):1686-92.
• 25% lower risk of bladder cancer among people with circulating vitamin D levels above 20 ng/mL (50 nmol/L) compared to the lowest levels in a large meta-analysis of 4 observational studies²⁷³Chen F, Li Q, Yu Y, Yang W, Shi F, Qu Y. Association of vitamin C, vitamin D, vitamin E and risk of bladder cancer: a dose-response meta-analysis. Scientific Reports. 2015 Apr 23;5:9599.
• 25% lower risk of bladder cancer among people with high serum 25-hydroxyvitamin D levels compared to low levels in a large meta-analysis of observational studies²⁷⁴Liao Y, Huang JL, Qiu MX, Ma ZW. Impact of serum vitamin D level on risk of bladder cancer: a systemic review and meta-analysis. Tumour Biology. 2015 Mar;36(3):1567-72.

Vitamin D intake: insufficient (conflicting) evidenceconflicting 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 vitamin D intake across many studies

• No evidence of an effect on risk of bladder cancer among people with high dietary vitamin D intake alone compared to low intake in a very large meta-analysis of 10 observational studies;²⁷⁵Boot IWA, Wesselius A et al. Dietary vitamin D intake and the bladder cancer risk: a pooled analysis of prospective cohort studies. Clinical Nutrition. 2023 Aug;42(8):1462-1474. see findings from this study that high dietary vitamin D intake combined with low calcium intake and moderate phosphorus intake was linked to lower risk below in “Vitamin D combined with other therapies”
• 32% higher risk of bladder cancer among people with the lowest intake of vitamin D compared to the highest in a large meta-analysis of 7 observational studies²⁷⁶Zhang H, Zhang H et al. Vitamin D deficiency and increased risk of bladder carcinoma: a meta-analysis. Cell Physiology and Biochemistry. 2015;37(5):1686-92.
• No evidence of an effect on risk of bladder cancer among people with the highest vitamin D intake from diet and supplements compared to the lowest intake in a large meta-analysis of 3 observational studies²⁷⁷Chen F, Li Q, Yu Y, Yang W, Shi F, Qu Y. Association of vitamin C, vitamin D, vitamin E and risk of bladder cancer: a dose-response meta-analysis. Scientific Reports. 2015 Apr 23;5:9599.

Also see evidence of higher risk of invasive breast cancer among postmenopausal women with vitamin D intakes higher than 600 IU/day along with calcium in Safety and precautions ›

Vitamin D levels

Recurrence: 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 risk of recurrence among people with breast cancer with higher 25(OH)D levels

• 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 studies²⁷⁸Li 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.
• 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 study²⁷⁹Yao 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.
• 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 studies²⁸⁰Li 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.
• 113% higher risk of recurrence among people with breast cancer with low vitamin D levels compared to high levels in a meta-analysis of 6 observational studies²⁸¹Rose AA, Elser C, Ennis M, Goodwin PJ. Blood levels of vitamin D and early stage breast cancer prognosis: a systematic review and meta-analysis. Breast Cancer Research and Treatment. 2013 Oct;141(3):331-9.

Cancer diagnosis: good evidence of higher risk of breast cancer among people with low 25(OH)D levels, and especially among premenopausal women

• Lower risk of breast cancer among people with serum vitamin D concentration higher than 40 ng/mL (100 nmol/mL) compared to lower levels in an average of results from 16 meta-analyses and observational studies²⁸²Torres A, Cameselle C, Otero P, Simal-Gandara J. The impact of vitamin D and its dietary supplementation in breast cancer prevention: an integrative review. Nutrients. 2024 Feb 20;16(5):573.
• Higher risk of breast cancer among people with 25(OH)D levels below either 20 ng/mL or 30 ng/mL (50 or 75 nmol/L) compared to higher levels in a meta-analysis of 25 observational studies²⁸³Voutsadakis 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.
• 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 studies²⁸⁴Song 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.
• Almost double the risk of breast cancer among women with 25(OH)D levels less than 10 ng/mL (25 nmol/L) compared to higher levels in a meta-analysis of 22 observational studies²⁸⁵Hossain 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 studies²⁸⁶Estébanez 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.
• 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 studies²⁸⁷Kim 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.

Vitamin D intake

Recurrence: 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 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 studies²⁸⁸Poole 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: Insufficient (conflicting) evidenceconflicting 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  risk of breast cancer among people with higher vitamin D intake

• 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 breast cancer among people treated with vitamin D supplements compared to controls in a large meta-analysis of 6 RCTs²⁸⁹Zhou L, Chen B, Sheng L, Turner A. The effect of vitamin D supplementation on the risk of breast cancer: a trial sequential meta-analysis. Breast Cancer Research and Treatment. 2020 Jul;182(1):1-8.
• 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 studies²⁹⁰Song 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.
• 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 studies²⁹¹Hossain 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 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 studies²⁹²Kim 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.
• 9% lower risk of breast cancer among people with the highest intake of vitamin D compared to the lowest in a meta-analysis of 11 observational studies²⁹³Chen P, Hu P et al. Meta-analysis of vitamin D, calcium and the prevention of breast cancer. Breast Cancer Research and Treatment. 2010 Jun;121(2):469-77.

Breast density, a risk factor for breast cancer

No evidence of an effect on breast density among women (mostly postmenopausal) with higher 25(OH)D levels in two studies

• No evidence of an effect on breast density among women (about ⅔ were postmenopausal) with higher 25(OH)D levels compared to lower levels in a mid-sized observational study²⁹⁴Knight JA, Vachon CM et al. No association between 25-hydroxyvitamin D and mammographic density. Cancer Epidemiology, Biomarkers & Prevention. 2006 Oct;15(10):1988-92.

Preliminarysignificant 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) and somewhat conflicting evidence of lower breast density among younger (under age 60) or premenopausal women with higher dietary vitamin D intake, but less evidence of an effect among older women

• No evidence of an effect on breast density among women with a mean age of 43 treated with 2,000 IU vitamin D 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 effects²⁹⁵Wood ME, Liu H et al. The influence of vitamin D on mammographic density: results from CALGB 70806 (Alliance) a randomized clinical trial. Cancer Prevention Research (Philadelphia). 2021 Jul;14(7):753-762.
• Lower mammographic density among women aged 50-59 treated with higher dietary vitamin D intake compared to low intake, but no evidence of an effect among older women in a mid-sized observational study²⁹⁶Bertone-Johnson ER, Chlebowski RT et al. Dietary vitamin D and calcium intake and mammographic density in postmenopausal women. Menopause. 2010 Nov-Dec;17(6):1152-60.
• No evidence of an effect on mammographic density among women around age 50 with higher dietary intakes of vitamin D compared to lower intakes in a large observational study²⁹⁷Mishra G, McCormack Vet al. Dietary calcium and vitamin D intakes in childhood and throughout adulthood and mammographic density in a British birth cohort. British Journal of Cancer. 2008 Nov 4;99(9):1539-43.
• Lower breast density among premenopausal women with higher intakes of vitamin D compared to low levels, but no evidence of an effect among postmenopausal women in a large observational study²⁹⁸Bérubé S, Diorio C et al. Vitamin D and calcium intakes from food or supplements and mammographic breast density. Cancer Epidemiology, Biomarkers & Prevention. 2005 Jul;14(7):1653-9.
• Lower breast density among women aged 40-60 with higher dietary intake of vitamin D compared to the lowest intake in a mid-sized observational study²⁹⁹Bérubé S, Diorio C, Verhoek-Oftedahl W, Brisson J. Vitamin D, calcium, and mammographic breast densities. Cancer Epidemiology, Biomarkers & Prevention. 2004 Sep;13(9):1466-72.

Preliminary evidence of lower breast density among women with a strong family history of breast cancer with the highest dietary intake of vitamin D

• Lower breast density among women with a strong family history of breast cancer with the highest dietary intake of vitamin D compared to the lowest in a mid-sized observational study³⁰⁰Tseng M, Byrne C, Evers KA, Daly MB. Dietary intake and breast density in high-risk women: a cross-sectional study. Breast Cancer Research. 2007;9(5):R72.

Preliminary evidence of lower breast density among premenopausal women with higher insulin-like growth factor (IGF)-1 levels and higher intake of vitamin D, but no evidence of an effect among women with lower IGF-1 levels

• Lower mammographic breast density among premenopausal women with higher insulin-like growth factor (IGF)-1 levels and higher intake of vitamin D compared to lower intake, but no evidence of an effect among women with lower IGF-1 levels in a mid-sized observational study³⁰¹Diorio C, Bérubé S et al. Influence of insulin-like growth factors on the strength of the relation of vitamin D and calcium intakes to mammographic breast density. Cancer Research. 2006 Jan 1;66(1):588-97.

Also see evidence of higher risk of advanced conventional adenomas among older adults treated with vitamin D3 and omega-3 fatty acids in Safety and precautions ›

Vitamin 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 risk of colorectal cancer incidence or mortality among people with higher 25(OH)D levels

• 20–39% lower risk of colorectal cancer among women with higher 25(OH)D levels compared to lower levels, but no evidence of an effect in men 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 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 studies³⁰²Hernández-Alonso P, Boughanem H et al. Circulating vitamin D levels and colorectal cancer risk: a meta-analysis and systematic review of case-control and prospective cohort studies. Critical Reviews in Food Science and Nutrition. 2023;63(1):1-17.
• 35% lower risk of colorectal cancer among people with high 25(OH)D levels compared to low levels in a meta-analysis of 4 meta-analyses of clinical trials³⁰³Arayici ME, Basbinar Y, Ellidokuz H. Vitamin D intake, serum 25-hydroxyvitamin-D (25(OH)D) levels, and cancer risk: a comprehensive meta-meta-analysis including meta-analyses of randomized controlled trials and observational epidemiological studies. Nutrients. 2023 Jun 12;15(12):2722.
• 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-analysis of 30 observational studies³⁰⁴Huang 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 (11 studies) and 20% lower risk of colorectal adenomas (22 studies) among people without cancer at baseline with higher 25(OH)D levels compared to lower levels in meta-analyses of observational studies³⁰⁵Huang 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.
• 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), with stronger effects among women than men, but no further benefit at higher levels in a large meta-analysis of 17 observational studies³⁰⁶McCullough 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 the highest 25(OH)D levels compared to the lowest in meta-analyses of 15,³⁰⁷Garland 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. 9,³⁰⁸Ma 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. 8,³⁰⁹Zhang 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. 5³¹⁰Touvier 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. and 15³¹¹Choi YJ, Kim YH, Cho CH, Kim SH, Lee JE. Circulating levels of vitamin D and colorectal adenoma: a case-control study and a meta-analysis. World Journal of Gastroenterology. 2015 Aug 7;21(29):8868-77. observational studies

Vitamin D intake as a whole

Good evidence of lower risk of colorectal cancer among people with higher total vitamin D intake

• 4% lower risk of colorectal cancer with each increase of 100 IU of vitamin D per day in a large meta-analysis of 23 observational studies³¹²Lopez-Caleya JF, Ortega-Valín L et al. The role of calcium and vitamin D dietary intake on risk of colorectal cancer: systematic review and meta-analysis of case-control studies. Cancer Causes & Control. 2022 Feb;33(2):167-182.
• 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 studies³¹³Boughanem 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.
• 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 very large meta-analyses of studies³¹⁴Huang 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 studies³¹⁵Huang 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.
• 13% lower risk of colorectal cancer among people with the highest intake of vitamin D compared to the lowest in a meta-analysis of 14 observational studies³¹⁶Liu Y, Yu Q et al. Vitamin and multiple-vitamin supplement intake and incidence of colorectal cancer: a meta-analysis of cohort studies. Medical Oncology. 2015 Jan;32(1):434.

Vitamin D from diet only: 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 slightly lower risk of colorectal cancer as a whole with each increase of 100 IU dietary vitamin D intake

• Slightly lower risk of colorectal cancer 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 studies³¹⁷Touvier 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

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 colorectal cancer among people taking vitamin D supplements

• No evidence of an effect on risk of colorectal cancer among people treated with vitamin D compared to placebo in a network meta-analysis of 32 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 effects³¹⁸Ma Y, You W et al. Chemoprevention of colorectal cancer in general population and high-risk population: a systematic review and network meta-analysis. Chinese Medical Journal (English). 2023 Apr 5;136(7):788-798.
• No evidence of an effect on risk of colorectal cancer among people treated with vitamin D supplements compared to placebo in a large meta-analysis of 9 RCTs³¹⁹Emmanouilidou G, Kalopitas G. Vitamin D as a chemopreventive agent in colorectal neoplasms. A systematic review and meta-analysis of randomized controlled trials. Pharmacology & Therapeutics. 2022 Sep;237:108252.

No evidence of an effect on risk of advanced metachronous neoplasia among people with previous colorectal neoplasia treated with vitamin D

• No evidence of an effect on reducing risk of advanced metachronous neoplasia among people with previous colorectal neoplasia treated with vitamin D compared to placebo in a network meta-analysis of 10 RCTs³²⁰Dulai PS, Singh S et al. Chemoprevention of colorectal cancer in individuals with previous colorectal neoplasia: systematic review and network meta-analysis. BMJ. 2016 Dec 5;355:i6188.

Esophageal cancer

Also see evidence of higher risk of adenocarcinoma or squamous cell carcinoma among people with higher 25(OH)D levels in Safety and precautions ›

Vitamin D intake

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 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 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 study³²¹Wang 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 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 esophageal neoplasia among people with higher vitamin D intake

• No evidence of an effect on risk of esophageal neoplasia, including adenocarcinoma, squamous cell carcinoma (SCC), Barrett’s esophagus, and squamous dysplasia, among people with higher vitamin D intake compared to low intake 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 observational studies³²²Zgaga L, O’Sullivan F et al. Markers of vitamin D exposure and esophageal cancer risk: a systematic review and meta-analysis. Cancer Epidemiology, Biomarkers & Prevention. 2016 Jun;25(6):877-86.

Liver cancer

Vitamin 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 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-analysis of 11 observational studies³²³Yi 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 studies³²⁴Guo 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 studies³²⁵Zhang 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.

Stomach cancer

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 serum vitamin D levels among people with gastric cancer compared to people without cancer and lower levels among people with more advanced cancer

• Lower serum vitamin D levels among people with gastric cancer compared to people without cancer, and lower levels among people with stage 3 or 4 cancer compared to stage 1 or 2, among people with with low differentiation of gastric cancer compared to well or moderately differentiated cancer, and among people with lymph node metastasis compared to without lymph node metastasis in a very large observational study³²⁶Zhao X, Wang J, Zou L. Vitamin D and gastric cancer—a systematic review and meta-analysis. Nutrición Hospitalaria. 2023 Oct 6;40(5):1080-1087. English.
• Lower serum 25(OH)D levels and higher risk of vitamin D deficiency among people with gastric cancer compared to controls, and lower levels among people with low differentiation of gastric cancer compared to well differentiated or moderately differentiated cancer in a meta-analysis of 9 observational studies³²⁷Liu X, Zhou Y, Zou X. Correlation between serum 25-hydroxyvitamin D levels and gastric cancer: a systematic review and meta-analysis. Current Oncology. 2022 Nov 2;29(11):8390-8400.

Vitamin D intake: no evidence of an effect on risk of stomach cancer among people with the highest intake of vitamin D in a combined analysis of studies

• No evidence of an effect on risk of stomach (gastric) cancer among people with the highest intake of vitamin D compared to the lowest in a meta-analysis of 4 observational studies³²⁸Chen X, Li L et al. Relationship of vitamin D intake, serum 25(OH) D, and solar ultraviolet-B radiation with the risk of gastric cancer: a meta-analysis. Journal of Cancer Research and Therapeutics. 2022 Sep;18(5):1417-1424.

Gynecologic cancer as a whole

Vitamin 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 risk of gynecologic cancer among people with higher serum vitamin D levels

• No evidence of an effect on risk of gynecologic cancer (female reproductive tumors) among people with higher serum vitamin 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 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 studies³²⁹Yan L, Gu Y et al. Associations between serum vitamin D and the risk of female reproductive tumors: a meta-analysis with trial sequential analysis. Medicine (Baltimore). 2018 Apr;97(15):e0360.

Cervical cancer

Vitamin D intake: 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 lower risk of recurrence of grade 1–3 disease among women with grade 2 or 3 cervical intraepithelial neoplasia treated with high-dose 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 effects³³⁰Vahedpoor 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.

Endometrial cancer: 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 a link between low vitamin D levels and polycystic ovary syndrome, a risk factor for endometrial cancer

• Lower serum 25(OH)D levels among people with polycystic ovary syndrome (PCOS) compared to people without PCOS in a meta-analysis of 14 observational studies³³¹Bacopoulou F, Kolias E, Efthymiou V, Antonopoulos CN, Charmandari E. Vitamin D predictors in polycystic ovary syndrome: a meta-analysis. European Journal of Clinical Investigation. 2017 Oct;47(10):746-755.
• Lower serum 25(OH)D levels among people with polycystic ovary syndrome compared to people without PCOS in a meta-analysis of 17 observational studies³³²Jia XZ, Wang YM et al. Effect of vitamin D on clinical and biochemical parameters in polycystic ovary syndrome women: a meta-analysis. Journal of Obstetrics and Gynaecology Research. 2015 Nov;41(11):1791-802.
• Lower serum 25(OH)D levels among people with polycystic ovary syndrome compared to people without PCOS in a meta-analysis of 16 observational studies³³³He C, Lin Z, Robb SW, Ezeamama AE. Serum vitamin D levels and polycystic ovary syndrome: a systematic review and meta-analysis. Nutrients. 2015 Jun 8;7(6):4555-77.

Vitamin 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 higher risk of head and neck cancer among people with low 25(OH)D levels

• 2.5 times the risk of oral cancer among people deficient in vitamin D compared to not deficient 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 studies³³⁴Patini R, Favetti Giaquinto E et al. Malnutrition as a risk factor in the development of oral cancer: a systematic literature review and meta-analyses. Nutrients. 2024 Jan 26;16(3):360.
• Lower risk of head and neck cancer among people with high 25(OH)D levels compared to lower levels in a large meta-analysis of 16 observational studies³³⁵Pu 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 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 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 study³³⁶Yokosawa 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 studies³³⁷Pu 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 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 risk of kidney cancer (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 studies³³⁸Wu 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 studies³³⁹Wu 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 levels

Goodsignificant 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) but somewhat conflicting evidence of higher risk of lung cancer among people with low 25(OH)D levels

Also see evidence that levels above about 35 ng/mL (87.5 nmol/L) are linked to increased mortality or risk of lung cancer in Safety and precautions ›

Because increased risk of lung cancer is seen at both very low and very high 25(OH)D levels, with lower risk at mid-range levels, comparing only the highest to the lowest levels, as in some of the studies here, may not give the whole picture.

• 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 lung cancer among people 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 3 meta-analyses of clinical trials³⁴⁰Arayici ME, Basbinar Y, Ellidokuz H. Vitamin D intake, serum 25-hydroxyvitamin-D (25(OH)D) levels, and cancer risk: a comprehensive meta-meta-analysis including meta-analyses of randomized controlled trials and observational epidemiological studies. Nutrients. 2023 Jun 12;15(12):2722.
• 28% lower risk of lung cancer among people with high circulating 25(OH)D levels compared to low levels in a large meta-analysis of 40 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 studies³⁴¹Sun K, Zuo M et al. Anti-tumor effect of vitamin D combined with calcium on lung cancer: a systematic review and meta-analysis. Nutrition and Cancer. 2021;73(11-12):2633-2642.
• An effect not in a straight line (nonlinear), 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-analysis of 12 observational studies³⁴²Wei 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 studies³⁴³Feng 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 mortality among people without lung cancer at baseline with the highest 25(OH)D levels compared to the lowest in a meta-analysis of 5 observational studies³⁴⁴Feng 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.
• 5% lower risk of lung cancer for each 10 nmol/L increment in 25(OH)D concentrations, with the greatest reductions in risk observed at 25(OH)D of nearly 21 ng/mL (53 nmol/L), and remained protective until approximately 36 ng/mL (90 nmol/L) in a meta-analysis of 10 observational studies³⁴⁵Chen GC, Zhang ZL et al. Circulating 25-hydroxyvitamin D and risk of lung cancer: a dose-response meta-analysis. Cancer Causes and Control. 2015 Dec;26(12):1719-28.
• 17% lower risk of lung cancer among people with the highest 25(OH)D levels compared to the lowest in a meta-analysis of 12 observational studies³⁴⁶Zhang L, Wang S, Che X, Li X. Vitamin D and lung cancer risk: a comprehensive review and meta-analysis. Cell Physiology and Biochemistry. 2015;36(1):299-305.

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 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 studies³⁴⁷Feng 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

• Lower risk of lung cancer among people with the highest vitamin D intake compared to the lowest in a meta-analysis of 3 meta-analyses of clinical trials³⁴⁸Arayici ME, Basbinar Y, Ellidokuz H. Vitamin D intake, serum 25-hydroxyvitamin-D (25(OH)D) levels, and cancer risk: a comprehensive meta-meta-analysis including meta-analyses of randomized controlled trials and observational epidemiological studies. Nutrients. 2023 Jun 12;15(12):2722.
• No evidence of an effect on risk of lung cancer among people treated with vitamin D compared to no vitamin D in a large meta-analysis of 40 observational studies³⁴⁹Sun K, Zuo M et al. Anti-tumor effect of vitamin D combined with calcium on lung cancer: a systematic review and meta-analysis. Nutrition and Cancer. 2021;73(11-12):2633-2642.
• 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 studies³⁵⁰Wei 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 studies³⁵¹Qian 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.

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 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 studies³⁵²Li 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 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 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 studies³⁵³Park 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.
• No evidence of an effect on risk of non-Hodgkin lymphoma or any subtypes (diffuse large B cell lymphoma, follicular lymphoma, small lymphocytic lymphomas/chronic lymphocytic leukemia, and T cell lymphoma) among people with the highest serum 25(OH)D levels compared to the lowest in a meta-analysis of 9 observational studies³⁵⁴Lu D, Chen J, Jin J. Vitamin D status and risk of non-Hodgkin lymphoma: a meta-analysis. Cancer Causes and Control. 2014 Nov;25(11):1553-63.

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 studies³⁵⁵Park 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 blood (hematological) cancer among adults with the highest total vitamin D

• No evidence of an effect on risk of hematological cancer among adults with the highest total vitamin D compared to the lowest in a meta-analysis of 5 observational studies³⁵⁶Psaltopoulou T, Ntanasis-Stathopoulos I et al. Micronutrient intake and risk of hematological malignancies in adults: a systematic review and meta-analysis of cohort studies. Nutrition and Cancer. 2018 Aug-Sep;70(6):821-839.

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 studies³⁵⁷Park 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.
• No evidence of an effect on risk of non-Hodgkin lymphoma or common subtypes (diffuse large B cell lymphoma, follicular lymphoma, small lymphocytic lymphomas/chronic lymphocytic leukemia, and T cell lymphoma) among people with the highest intake of vitamin D compared to the lowest in a meta-analysis of 9 observational studies³⁵⁸Lu D, Chen J, Jin J. Vitamin D status and risk of non-Hodgkin lymphoma: a meta-analysis. Cancer Causes and Control. 2014 Nov;25(11):1553-63.

Vitamin D levels

Recurrence: 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 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 effects³⁵⁹Johansson 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 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 study³⁶⁰Lipplaa 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

Good evidence of higher risk of melanoma incidence or more advanced stage  among people with vitamin D deficiency

Our note: we have seen a U-shaped curve for the effect of vitamin D and cancer outcomes in many studies of other cancer types, which could mean that the benefit from vitamin D blood levels is strongest toward the middle of the range. If that’s true for melanoma or other skin cancers, comparing only the highest level to the lowest may miss the true effect.

See evidence of a higher risk of skin cancer among people with high levels of vitamin D in Safety and precautions ›

• 45% higher risk of cutaneous melanoma and higher risk of more advanced melanoma among people with 25(OH)D levels below 20 ng/mL 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 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 of 14 observational studies³⁶¹Shellenberger RA, Gowda S, Kurn H, Albright J, Mayo MH. Vitamin D insufficiency and serum levels related to the incidence and stage of cutaneous melanoma: a systematic review and meta-analysis. Melanoma Research. 2023 Aug 1;33(4):265-274.
• No evidence of an effect on risk of melanoma among people with the highest vitamin D serum levels compared to the lowest in a large meta-analysis of 6 observational studies³⁶²Song Y, Lu H, Cheng Y. To identify the association between dietary vitamin D intake and serum levels and risk or prognostic factors for melanoma-systematic review and meta-analysis. BMJ Open. 2022 Aug 26;12(8):e052442.
• 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-analysis of 25 observational studies³⁶³Tsai 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.
• No evidence of an effect on risk of melanoma with a decrease of 8 ng/mL (20 ng/L) in a very large observational study³⁶⁴Liyanage UE, Law MH; Melanoma Meta-analysis Consortium; Barrett JH, Iles MM, MacGregor S. Is there a causal relationship between vitamin D and melanoma risk? A Mendelian randomization study. British Journal of Dermatology. 2020 Jan;182(1):97-103.
• 46% higher risk of cutaneous melanoma and 64% higher risk of non-melanoma skin cancer among people with the lowest vitamin D serum levels compared to the highest in a meta-analysis of 20 observational studies³⁶⁵Caini S, Boniol M et al. Vitamin D and melanoma and non-melanoma skin cancer risk and prognosis: a comprehensive review and meta-analysis. European Journal of Cancer. 2014 Oct;50(15):2649-58.

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 study³⁶⁶Samimi 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: insufficient (contradictory) evidenceconflicting 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 incidence of 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 study³⁶⁷Kanasuo 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.
• No evidence of an effect on risk melanoma among people with the highest intake of vitamin D compared to the lowest in a very large meta-analysis of 6 observational studies³⁶⁸Song Y, Lu H, Cheng Y. To identify the association between dietary vitamin D intake and serum levels and risk or prognostic factors for melanoma-systematic review and meta-analysis. BMJ Open. 2022 Aug 26;12(8):e052442.
• No evidence of an effect on risk of basal cell carcinoma or cutaneous squamous cell carcinoma at 8 years of follow-up among people treated with 1000 IU vitamin D3 per day for 3 or 5 years compared to placebo in a very large RCT³⁶⁹Passarelli 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.
• No evidence of an effect on risk of cutaneous melanoma or nonmelanoma skin cancer among people with the highest vitamin D intake compared to the lowest in a meta-analysis of 20 observational studies³⁷⁰Caini S, Boniol M et al. Vitamin D and melanoma and non-melanoma skin cancer risk and prognosis: a comprehensive review and meta-analysis. European Journal of Cancer. 2014 Oct;50(15):2649-58.

Topical vitamin D: preliminary evidence of lower total lesion counts among people with multiple acral actinic keratoses treated with a topical synthetic vitamin D

• Lower total lesion count among people with multiple acral actinic keratoses treated with topical tacalcitol (a synthetic vitamin D) along with photodynamic therapy (PD) with topical 5-aminolevulinic acid (ALA) for 15 consecutive days before PD and ALA compared to PD and ALA alone in a small RCT³⁷¹Borgia F, Riso G et al. Topical tacalcitol as neoadjuvant for photodynamic therapy of acral actinic keratoses: an intra-patient randomized study. Photodiagnosis and Photodynamic Therapy. 2020 Sep;31:101803.

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 higher risk of ovarian cancer among people with low circulating vitamin D levels

• 37% lower risk of ovarian cancer among people with the highest blood 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 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 studies³⁷²Jung S, Jin S, Je Y. Vitamin D intake, blood 25-hydroxyvitamin D, and risk of ovarian cancer: a meta-analysis of observational studies. Journal of Women’s Health (Larchmont). 2023 May;32(5):561-573.
• 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-analysis of 4 observational studies³⁷³Liao 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: insufficient (conflicting) evidenceconflicting 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 risk of ovarian cancer among people with higher dietary vitamin D intake

• 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 ovarian cancer among people with the highest intake of vitamin D compared to the lowest in a meta-analysis of 4 observational studies³⁷⁴Jung S, Jin S, Je Y. Vitamin D intake, blood 25-hydroxyvitamin D, and risk of ovarian cancer: a meta-analysis of observational studies. Journal of Women’s Health (Larchmont). 2023 May;32(5):561-573.
• 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 studies³⁷⁵Xu 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 studies³⁷⁶Liao 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.

Also see evidence of higher risk of pancreatic cancer among people with high vitamin D levels in Safety and precautions ›

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 higher mortality from pancreatic cancer 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 risk of pancreatic cancer among people with low 25(OH)D levels in combined analyses of studies

• Moderately lower pancreatic cancer mortality (6 studies) but no evidence of an effect on risk of pancreatic cancer (10 studies) among people with the highest 25(OH)D levels compared to the lowest in large 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 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 studies³⁷⁷Shen Y, Xia J et al. The association between circulating 25-hydroxyvitamin D and pancreatic cancer: a systematic review and meta-analysis of observational studies. European Journal of Nutrition. 2024 Apr;63(3):653-672.
• 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-analysis of 5 observational studies³⁷⁸Zhang 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.
• No evidence of an effect on risk of pancreatic cancer among people with the highest 25(OH)D levels compared to the lowest in a very large meta-analysis of 9 observational studies³⁷⁹Liu SL, Zhao YP et al. Vitamin D status and the risk of pancreatic cancer: a meta-analysis. Chinese Medical Journal (English). 2013;126(17):3356-9.

Vitamin D intake: 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 risk of pancreatic cancer among people with higher vitamin D intake, especially nonsmoking people

• 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 observational studies;³⁸⁰Liu 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.
• 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 studies³⁸¹Zhang 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.
• Lower risk of pancreatic cancer among nonsmoking people with the highest total vitamin D intake (from diet and supplements) compared to no intake but no evidence of an effect among smokers in a very large meta-analysis of 16 observational studies³⁸²Genkinger JM, Wang M et al. Dairy products and pancreatic cancer risk: a pooled analysis of 14 cohort studies. Annals of Oncology. 2014 Jun;25(6):1106-15.

Also see evidence of higher risk of prostate cancer among people with the highest levels of vitamin D in Safety and precautions ›

Vitamin 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 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 study³⁸³Kristal 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.
• 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 prostate cancer with each 10 ng/mL increase in 25(OH)D levels in a meta-analysisa statistical analysis that combines the results of two or more research studies; the results of smaller research studies addressing the same or similar questions can be analyzed as though they are one bigger, more powerful study of 10 observational studies³⁸⁴Yin L, Raum E, Haug U, Arndt V, Brenner H. Meta-analysis of longitudinal studies: serum vitamin D and prostate cancer risk. Cancer Epidemiology. 2009 Dec;33(6):435-45.
• 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 study³⁸⁵Tuohimaa 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 study³⁸⁶Tuohimaa 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 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 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 study³⁸⁷Batai 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 effects³⁸⁸Chandler 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 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 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 quality³⁸⁹Zhao 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 quality³⁹⁰Zhao 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 studies³⁹¹Hu 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.

Vitamin D and calcium

Cancer as a whole: 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 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 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 effects³⁹²Lappe 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.

Bladder cancer: 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 lower risk of bladder cancer among people with high dietary vitamin D intake combined with moderate calcium intake and low phosphorus intake

• 23% lower risk of bladder cancer among people with high dietary vitamin D intake combined with moderate calcium intake and low phosphorus intake compared to other intakes 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 10 observationala type of study in which individuals are observed or certain outcomes are measured, but no attempt is made to affect the outcome (for example, no treatment is given); an example is a study that records people’s diets, but doesn’t try to alter their diets, and looks for patterns of disease or other outcomes related to different foods studies³⁹³Boot IWA, Wesselius A et al. Dietary vitamin D intake and the bladder cancer risk: a pooled analysis of prospective cohort studies. Clinical Nutrition. 2023 Aug;42(8):1462-1474.

Blood cancer: strong 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 RCT³⁹⁴Ammann 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: strong evidence of slightly lower risk of breast cancer mortality but no evidence of an effect on risk of breast cancer among people treated with calcium plus vitamin D, but see also an increased risks 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 RCT³⁹⁵Thomson 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.
• 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 breast cancer among people treated with vitamin D and calcium supplements compared to controls in a large meta-analysis of 6 RCTs³⁹⁶Zhou L, Chen B, Sheng L, Turner A. The effect of vitamin D supplementation on the risk of breast cancer: a trial sequential meta-analysis. Breast Cancer Research and Treatment. 2020 Jul;182(1):1-8.
• 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 RCT³⁹⁷Cauley 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.
• Lowest risk of breast cancer among people with dietary calcium intake of about 600 mg/day, dietary vitamin D intake of about 400 IU/day, and serum vitamin D levels of about 30 ng/ml (75 nmol/L) in a meta-analysis of observational studies³⁹⁸Hong Z, Tian C, Zhang X. Dietary calcium intake, vitamin D levels, and breast cancer risk: a dose-response analysis of observational studies. Breast Cancer Research and Treatment. 2012 Nov;136(1):309-12.

No evidence of an effect on mammographic density—a risk factor for breast cancer—among postmenopausal women treated with calcium plus vitamin D in one study

• No evidence of an effect on mammographic density among postmenopausal women treated with 1000 mg of elemental calcium carbonate plus 400 IU of vitamin D3 a day compared to placebo in a mid-sized RCT³⁹⁹Bertone-Johnson ER, McTiernan A et al. Vitamin D and calcium supplementation and one-year change in mammographic density in the women’s health initiative calcium and vitamin D trial. Cancer Epidemiology, Biomarkers & Prevention. 2012 Mar;21(3):462-73.

Colorectal cancer

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 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 RCT⁴⁰⁰Grau 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 evidencepreclinical evidence only OR 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 (this is the CancerChoices definition; other researchers and studies may define this differently) 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 RCT⁴⁰¹Cauley 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 RCT⁴⁰²Ding 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.

Lung cancer: insufficient (conflicting) evidenceconflicting 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 risk of lung cancer among people treated with vitamin D and calcium

• 19% lower risk of lung cancer among people treated with vitamin D and calcium compared to neither in a large meta-analysis of 40 observational studies⁴⁰³Sun K, Zuo M et al. Anti-tumor effect of vitamin D combined with calcium on lung cancer: a systematic review and meta-analysis. Nutrition and Cancer. 2021;73(11-12):2633-2642.
• No evidence of an effect on risk of lung cancer among postmenopausal women treated with vitamin D and calcium compared to placebo in a meta-analysis of 3 RCTs⁴⁰⁴Cortés-Jofré M, Rueda JR, Asenjo-Lobos C, Madrid E, Bonfill Cosp X. Drugs for preventing lung cancer in healthy people. Cochrane Database of Systematic Reviews. 2020 Mar 4;3(3):CD002141.

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 RCT⁴⁰⁵Passarelli 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

Strong 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, but no evidence of an effect on risk of melanoma among women without a history of non-melanoma skin cancer

• 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 RCT⁴⁰⁶Tang 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 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 effects⁴⁰⁷Song 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, 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 combined 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 RCT⁴⁰⁸Bischoff-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.