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 evidence of more lymphoma-related symptoms among people with low levels of 25(OH)D

• A weak trendan apparent change due to a therapy, close to but not achieving full statistical significance (this is the CancerChoices definition; other researchers and studies may define this differently toward higher incidence of lymphoma-related symptoms among people with previously untreated lymphoma with low levels of 25(OH)D (variably defined across studies) compared to higher levels in a meta-analysisa statistical analysis that combines the results of two or more research studies; the results of smaller research studies addressing the same or similar questions can be analyzed as though they are one bigger, more powerful study of 3 observationala type of study in which individuals are observed or certain outcomes are measured, but no attempt is made to affect the outcome (for example, no treatment is given); an example is a study that records people’s diets, but doesn’t try to alter their diets, and looks for patterns of disease or other outcomes related to different foods studies¹⁴⁵Tao Y, Chen H, Zhou Y, Shi Y. Meta-analysis of the prognostic and clinical value of serum 25-hydroxyvitamin D levels in previously untreated lymphoma. Future Oncology. 2021 May;17(14):1825-1838.

Weak evidence of fewer endocrine symptoms and less bone pain and fatigue among clinically stable women with estrogen receptor-positive metastatic breast cancer and insufficient serum 25-hydroxyvitamin D levels treated with high-dose repletion therapy

• Weak trendsan apparent change due to a therapy, close to but not achieving full statistical significance (this is the CancerChoices definition; other researchers and studies may define this differently) toward fewer endocrine symptoms and less bone pain and fatigue among clinically stable women with estrogen receptor-positive metastatic breast cancer and insufficient serum 25-hydroxyvitamin D levels treated with high-dose repletion therapy for 8 weeks compared to baseline in a small uncontrolled triala study in which a therapy is used, but without a comparison group against which to judge outcomes; an uncontrolled trial is considered a weak study design¹⁴⁶Sheean PM, Robinson P et al. Associations between cholecalciferol supplementation and self-reported symptoms among women with metastatic breast cancer and vitamin d deficiency: a pilot study. Oncology Nursing Forum. 2021 May 1;48(3):352-360.

Weak evidence of increased weight, body mass index (BMI), and fat-free mass (FFM) during chemotherapy among people with colorectal cancer treated with vitamin D

• Increased weight, body mass index (BMI), and fat-free mass (FFM) during chemotherapy among people with colorectal cancer treated with 50,000 IU vitamin D3 soft gel weekly, either with or without 660mg omega-3 fatty acid supplements daily, for 8 weeks compared to baseline in an uncontrolled analysisan analysis in which a therapy is used, but without a comparison group against which to judge outcomes within a small RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects¹⁴⁷Haidari F, Abiri B, Iravani M, Ahmadi-Angali K, Vafa M. Randomized study of the effect of vitamin D and omega-3 fatty acids cosupplementation as adjuvant chemotherapy on inflammation and nutritional status in colorectal cancer patients. Journal of Dietary Supplements. 2020;17(4):384-400.

Preliminary evidence of better muscle function among people with prostate cancer treated with vitamin D

• A better marker of muscle health (bioelectrical impedance) among people aged 60 or older with prostate cancer treated with 600 IU/day plus 50,000 IU/week vitamin D compared to 600 IU/day plus placebo weekly for 24 weeks in a small RCT¹⁴⁸Inglis JE, Fernandez ID et al. Effects of High-Dose Vitamin D Supplementation on Phase Angle and Physical Function in Patients with Prostate Cancer on ADT. Nutrition and Cancer. 2021;73(10):1882-1889.
• Better muscle strength among 37% of people with advanced hormone refractory prostate cancer treated with 2,000 units oral vitamin D daily for 12 weeks compared to baseline in a small uncontrolled triala study in which a therapy is used, but without a comparison group against which to judge outcomes; an uncontrolled trial is considered a weak study design¹⁴⁹Van Veldhuizen PJ, Taylor SA, Williamson S, Drees BM. Treatment of vitamin D deficiency in patients with metastatic prostate cancer may improve bone pain and muscle strength. Journal of Urology. 2000 Jan;163(1):187-90.

Loss of bone density and impacts on teeth and bones is a common side effect of treatment with systemic corticosteroids, exemestane, or androgen deprivation therapy. Also see clinical practice guidelines relating to bone health in Are you a health professional? ›

• A weak trend toward less loss of bone mineral density at the femoral neck during treatment with adjuvant anastrozole among women with early breast cancer and aromatase inhibitor-induced musculoskeletal symptoms treated with 50,000 IU vitamin D2 capsules weekly, converting to monthly depending on baseline 25(OH)D levels, compared to placebo in a small RCT¹⁵⁰Rastelli AL, Taylor ME et al. Vitamin D and aromatase inhibitor-induced musculoskeletal symptoms (AIMSS): a phase II, double-blind, placebo-controlled, randomized trial. Breast Cancer Research and Treatment. 2011 Aug;129(1):107-16.
• Substantially lower total hip bone loss and a weak trend toward less femoral neck and trochanter bone loss, but no evidence of an effect on lumbar spine bone loss, within 6 months of starting androgen deprivation therapy (ADT) and with 6 more planned months of ADT among people 60 years or older with prostate cancer and with 25(OH)D levels below 32 ng/ml treated with supplemental 600 IU/daily vitamin D plus 1,000 mg/day calcium further treated with high-dose 50,000 IU/weekly vitamin D compared to placebo for 24 weeks in a small RCT¹⁵¹Peppone LJ, Mustian KM et al. A phase II RCT of high-dose vitamin D supplementation for androgen deprivation therapy (ADT)-induced bone loss among older prostate cancer (PCa) patients.  Journal of Clinical Oncology 35, 10113–10113, 2017.

• Less fatigue among people with advanced cancer admitted to palliative care and with 25(OH)D levels less than 20 ng/mL (50 nmol/L) treated with 4000 IU vitamin D/day for 12 weeks compared to placebo in a mid-sized RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects¹⁵²Helde Frankling M, Klasson C et al. ‘Palliative-D’—vitamin D supplementation to palliative cancer patients: a double blind, randomized placebo-controlled multicenter trial. Cancers (Basel). 2021 Jul 23;13(15):3707.

• Lower 25(OH)D levels among people with cancer with more severe (grade 2–3) chemotherapy-induced peripheral neuropathy (CIPN) compared to grade 0–1 CIPN in all 4 observationala type of study in which individuals are observed or certain outcomes are measured, but no attempt is made to affect the outcome (for example, no treatment is given); an example is a study that records people’s diets, but doesn’t try to alter their diets, and looks for patterns of disease or other outcomes related to different foods studies analyzed in a review¹⁵³Tofthagen C, Tanay M et al. A systematic review of nutritional lab correlates with chemotherapy induced peripheral neuropathy. Journal of Clinical Medicine. 2022 Jan 12;11(2):355.

• Substantially less oral mucositis during radiotherapy among people with head and neck cancer treated with a topical oral vitamin D gel, either with or without conventional treatment for oral mucositis, compared to no vitamin D in a small RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects¹⁵⁴Bakr IS, Zaki AM, El-Moslemany RM, Elsaka RO. Vitamin D oral gel for prevention of radiation-induced oral mucositis: a randomized clinical trial. Oral Diseases. 2021 Jul;27(5):1197-1204.

General cancer pain: preliminary evidence of less opioid use among people with advanced cancer with 25(OH)D levels less than 20 ng/mL treated with vitamin D

• Moderately smaller increase of opioid (fentanyl) use among people with advanced cancer admitted to palliative care and with 25(OH)D levels less than 20 ng/mL (50 nmol/L) treated with 4000 IU vitamin D/day for 12 weeks compared to placebo in a mid-sized RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects¹⁵⁵Helde Frankling M, Klasson C et al. ‘Palliative-D’—vitamin D supplementation to palliative cancer patients: a double blind, randomized placebo-controlled multicenter trial. Cancers (Basel). 2021 Jul 23;13(15):3707.

Pain related to hormone therapy: modest evidence of lower pain during hormone therapy among people treated with vitamin D, and especially among people starting with lower 25(OH)D levels

• Lower scores on Brief Pain Inventory and a weak trend toward fewer aromatase inhibitor-associated musculoskeletal symptoms among women with stage 1–3 breast cancer starting adjuvant letrozole and with 25(OH)D levels of 40 ng/mL or lower treated with standard daily supplement of 1200 mg calcium and 600 IU vitamin D3 further receiving 30,000 IU oral vitamin D compared to the standard supplement and placebo in a mid-sized RCT¹⁵⁶Khan QJ, Kimler BF, et al. Randomized trial of vitamin D3 to prevent worsening of musculoskeletal symptoms in women with breast cancer receiving adjuvant letrozole. The VITAL trial. Breast Cancer Research and Treatment. 2017 Nov;166(2):491-500.
• Lower measures of pain and pain interference at 2 months during treatment with adjuvant anastrozole, with stronger effects among women with lower baseline 25(OH)D levels, among women with early breast cancer and aromatase inhibitor-induced musculoskeletal symptoms treated with 50,000 IU vitamin D2 capsules weekly, converting to monthly treatment depending on baseline 25(OH)D levels, compared to placebo in a small RCT¹⁵⁷Rastelli AL, Taylor ME et al. Vitamin D and aromatase inhibitor-induced musculoskeletal symptoms (AIMSS): a phase II, double-blind, placebo-controlled, randomized trial. Breast Cancer Research and Treatment. 2011 Aug;129(1):107-16.
• Less disability from joint pain after 16 weeks of letrozole among women initiating adjuvant letrozole for breast cancer with baseline 25(OH)D levels of 40 ng/mL or less treated for 4 weeks with standard dose calcium and vitamin D, then further treated with 50,000 IU per week for 12 weeks and achieving 25(OH)D levels higher than 66 ng/mL compared to lower levels in a small RCT¹⁵⁸Khan QJ, Reddy PS et al. Effect of vitamin D supplementation on serum 25-hydroxy vitamin D levels, joint pain, and fatigue in women starting adjuvant letrozole treatment for breast cancer. Breast Cancer Research and Treatment. 2010 Jan;119(1):111-8.
• A smaller increase in joint pain among women starting aromatase inhibitor therapy who attained concentrations of 25(OH)D of 40 ng/mL or higher through supplementation compared to lower levels in a mid-sized observationala type of study in which individuals are observed or certain outcomes are measured, but no attempt is made to affect the outcome (for example, no treatment is given); an example is a study that records people’s diets, but doesn’t try to alter their diets, and looks for patterns of disease or other outcomes related to different foods study¹⁵⁹Prieto-Alhambra D, Javaid MK et al. Vitamin D threshold to prevent aromatase inhibitor-induced arthralgia: a prospective cohort study. Breast Cancer Research and Treatment. 2011 Feb;125(3):869-78.
• Comparable effects on aromatase inhibitor-associated musculoskeletal symptoms including general musculoskeletal pain, joint pain, and muscle stiffness among postmenopausal women with stage 1–3a breast cancer treated with either 600 IU or 4000 IU vitamin D3 daily for 6 months, and so no evidence of added benefit from the higher dose, in a mid-sized uncontrolled trial¹⁶⁰Shapiro AC, Adlis SA et al. Randomized, blinded trial of vitamin D3 for treating aromatase inhibitor-associated musculoskeletal symptoms (AIMSS). Breast Cancer Research and Treatment. 2016 Feb;155(3):501-12.
• No evidence of an effect on development of joint pain (arthralgia), although higher serum vitamin D levels were achieved, during adjuvant aromatase inhibitor therapy among postmenopausal women treated with 50,000 IU vitamin D3 weekly for 12 weeks followed by 2000 IU daily for 40 weeks compared to 800 IU daily for 52 weeks in a small RCT¹⁶¹Niravath P, Hilsenbeck SG et al. Randomized controlled trial of high-dose versus standard-dose vitamin D3 for prevention of aromatase inhibitor-induced arthralgia. Breast Cancer Research and Treatment. 2019 Sep;177(2):427-435.
• Lower pain scores among 25% of people with advanced hormone refractory prostate cancer treated with 2,000 units oral vitamin D daily for 12 weeks compared to baseline in a small uncontrolled trial¹⁶²Van Veldhuizen PJ, Taylor SA, Williamson S, Drees BM. Treatment of vitamin D deficiency in patients with metastatic prostate cancer may improve bone pain and muscle strength. Journal of Urology. 2000 Jan;163(1):187-90.

Pain related to surgery

No evidence of an effect on pain after brain tumor surgery among people with vitamin D serum levels of 20 ng/dL or lower treated with vitamin D before surgery in a small study

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

• No evidence of an effect on pain, although higher serum vitamin D levels were achieved, after brain tumor surgery among people with vitamin D serum levels of 20 ng/dL or lower treated with an intramuscular injection of 300,000 IU vitamin D before surgery compared to no treatment in a small RCT¹⁶³Hajimohammadebrahim-Ketabforoush M, Shahmohammadi M, Khoundabi B, Shariatpanahi ZV. Effect of vitamin D supplementation on postcraniotomy pain after brain tumor surgery: a randomized clinical trial. World Neurosurgery. 2019 Oct;130:e105-e111.
• Lower pain threshold, opioid and analgesic use, and pain scores after colorectal cancer surgery among people with sufficient vitamin D levels (20 ng/mL or higher) compared to deficient levels (less than 20 ng/mL) in a mid-sized observational study¹⁶⁴Xia J, Li D, Yu G, et al. Effects of hypovitaminosis D on preoperative pain threshold and perioperative opioid use in colorectal cancer surgery: a cohort study. Pain Physician. 2022;25(7):E1009-E1019.

• Higher levels of self-reported health-related quality of life at study enrollment and 6 months later among women with breast cancer taking vitamin D supplements compared to no supplements in a mid-sized observationala type of study in which individuals are observed or certain outcomes are measured, but no attempt is made to affect the outcome (for example, no treatment is given); an example is a study that records people’s diets, but doesn’t try to alter their diets, and looks for patterns of disease or other outcomes related to different foods study¹⁶⁵Andersen MR, Sweet E et al. Effects of vitamin D use on health-related quality of life of breast cancer patients in early survivorship. Integrative Cancer Therapies. 2019 Jan-Dec;18:1534735418822056.
• Higher levels of self-reported health-related quality of life 6 months after study enrollment among women with breast cancer with sufficient vitamin D levels (30 ng/mL or higher) compared to lower levels in a mid-sized observational study¹⁶⁶Andersen MR, Sweet E et al. Effects of vitamin D use on health-related quality of life of breast cancer patients in early survivorship. Integrative Cancer Therapies. 2019 Jan-Dec;18:1534735418822056.

• Less vaginal atrophy during tamoxifen treatment among women with breast cancer treated with vaginal vitamin D suppositories every evening before bedtime for 8 weeks compared to placebo in a mid-sized RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects¹⁶⁷Keshavarzi Z, Janghorban R, Alipour S, Tahmasebi S, Jokar A. The effect of vitamin D and E vaginal suppositories on tamoxifen-induced vaginal atrophy in women with breast cancer. Supportive Care in Cancer. 2019 Apr;27(4):1325-1334

• Higher severity of radiation-induced acute proctitis after 5 weeks of radiation therapy among people with vitamin D deficiency (less than 14 ng/mL or 35 nmol/L for males and less than 16 ng/mL or 40 nmol/L in for females) compared to higher levels in a small observationala type of study in which individuals are observed or certain outcomes are measured, but no attempt is made to affect the outcome (for example, no treatment is given); an example is a study that records people’s diets, but doesn’t try to alter their diets, and looks for patterns of disease or other outcomes related to different foods study¹⁶⁸Ghorbanzadeh-Moghaddam A, Gholamrezaei A, Hemati S. Vitamin D deficiency is associated with the severity of radiation-induced proctitis in cancer patients. International Journal of Radiation Oncology, Biology, Physics. 2015 Jul 1;92(3):613-8.

Cardiovascular symptoms: no evidence of an effectoverall, one or more studies did not demonstrate that a treatment or intervention led to an expected outcome; this does not always mean that there is no effect in clinical practice, but that the studies may have been underpowered (too few participants) or poorly designed. Larger, well-designed studies provide more confidence in making assessments. on markers of vascular health among people with chronic fatigue syndrome treated with vitamin D

• No evidence of an effect on markers of vascular health (stiffness measured using carotid-femoral pulse wave velocity, dilatation of the brachial artery, blood pressure, or cholesterol) among people with chronic fatigue syndrome treated with 100,000 IU oral vitamin D3 every 2 months for 6 months compared to placebo in a small RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects¹⁶⁹Witham MD, Adams F et al. Effect of intermittent vitamin D3 on vascular function and symptoms in chronic fatigue syndrome–a randomised controlled trial. Nutrition, Metabolism & Cardiovascular Diseases. 2015 Mar;25(3):287-94.

Cognitive difficulties: modest evidence of lower incidence of dementia and longer dementia-free survival among people taking vitamin D supplements prior to dementia onset

• Lower incidence of dementia and longer dementia-free survival among people taking vitamin D supplements prior to dementia onset in a very large observationala type of study in which individuals are observed or certain outcomes are measured, but no attempt is made to affect the outcome (for example, no treatment is given); an example is a study that records people’s diets, but doesn’t try to alter their diets, and looks for patterns of disease or other outcomes related to different foods study¹⁷⁰Ghahremani M, Smith EE et al. Vitamin D supplementation and incident dementia: effects of sex, APOE, and baseline cognitive status. Alzheimers & Dementia (Amsterdam). 2023 Mar 1;15(1):e12404.

Depression or negative emotions: strong evidenceconsistent, significant effects in several large (or at least one very large) well designed clinical studies or at least two meta-analyses of clinical studies of moderate or better quality (or one large meta-analysis) finding similar results (this is the CancerChoices definition; other researchers and studies may define this differently) of less negative emotion or fewer symptoms of depression among people with clinically significant depressive symptoms or depressive disorder treated with vitamin D

• Less negative emotion among people with major depressive disorder or with 25(OH)D levels less than 20 ng/mL (50 nmol/L) treated with up to 4,000 IU vitamin D per day for 8 weeks or longer compared to controls in a meta-analysisa statistical analysis that combines the results of two or more research studies; the results of smaller research studies addressing the same or similar questions can be analyzed as though they are one bigger, more powerful study of 25 RCTsrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects¹⁷¹Cheng YC, Huang YC, Huang WL. The effect of vitamin D supplement on negative emotions: a systematic review and meta-analysis. Depression and Anxiety. 2020 Jun;37(6):549-564.
• Moderately lower depressive symptom ratings among people with major depression treated with vitamin D compared to controls in a meta-analysis of 4 RCTs¹⁷²Vellekkatt F, Menon V. Efficacy of vitamin D supplementation in major depression: a meta-analysis of randomized controlled trials. Journal of Postgraduate Medicine. Apr-Jun 2019;65(2):74-80.
• Moderately fewer depressive symptoms among people with clinically significant depressive symptoms or depressive disorder, but no evidence of an effect among people without clinically significant depression, treated with vitamin D compared to controls in a meta-analysis of 2 RCTs¹⁷³Shaffer JA, Edmondson D et al. Vitamin D supplementation for depressive symptoms: a systematic review and meta-analysis of randomized controlled trials. Psychosomatic Medicine. 2014 Apr;76(3):190-6.

Fatigue: insufficient evidencepreclinical evidence only OR clinical studies with such poor or unclear methodology that no conclusion can be drawn OR conflicting findings across clinical studies with no preponderance of evidence in one direction; conflicting evidence occurs when studies find conflicting effects (positive effect vs no effect or negative effect) with the same treatment and the same general study population (same cancer type, for example) (this is the CancerChoices definition; other researchers and studies may define this differently) of an effect on fatigue among people with fatigue treated with vitamin D

• Lower fatigue scores 4 weeks after treatment among people with fatigue and 25(OH)D levels less than 8 ng/mL (20 nmol/L) treated with a single 100,000 IU oral dose of vitamin D3 compared to placebo, and lower fatigue scores related to rises in 25(OH)D levels, in a mid-sized RCT¹⁷⁴Nowak A, Boesch L et al. Effect of vitamin D3 on self-perceived fatigue: a double-blind randomized placebo-controlled trial. Medicine (Baltimore). 2016 Dec;95(52):e5353.
• No evidence of an effect on fatigue scores among people with chronic fatigue syndrome treated with 100,000 IU oral vitamin D3 every 2 months for 6 months compared to placebo in a small RCT¹⁷⁵Witham MD, Adams F et al. Effect of intermittent vitamin D3 on vascular function and symptoms in chronic fatigue syndrome–a randomised controlled trial. Nutrition, Metabolism & Cardiovascular Diseases. 2015 Mar;25(3):287-94.

Neurological symptoms: preliminary evidence of less severe peripheral neuropathy among people with diabetes and neuropathy treated with vitamin D

• Less severe peripheral neuropathy among people with diabetes and neuropathy treated with 40,000 IU vitamin D (cholecalciferol) per week for 24 weeks compared to 5000 IU per week in a small RCT¹⁷⁶Karonova T, Stepanova A, Bystrova A, Jude EB. High-dose vitamin D supplementation improves microcirculation and reduces inflammation in diabetic neuropathy patients. Nutrients. 2020 Aug 20;12(9):2518.

Pain: good evidencesignificant effects in one large or several mid-sized and well-designed clinical studies (randomized controlled trials (RCTs) with an appropriate placebo or other strong comparison control or observational studies that control for confounds) (this is the CancerChoices definition; other researchers and studies may define this differently) of fewer requests for pain medication but no evidence of an effect on pain scores overall among people with vitamin D levels below 20 ng/mL treated with vitamin D

• No evidence of an effect on pain scores among people treated with monthly 100,000-IU capsules of vitamin D3 over roughly 3 years compared to placebo, but fewer requests for nonsteroidal anti-inflammatory drugs among people with vitamin D levels below 20 ng/mL (50 nmol/L) compared to higher levels in a very large RCT¹⁷⁷Wu Z, Camargo CA Jr et all. Monthly vitamin D supplementation, pain, and pattern of analgesic prescription: secondary analysis from the randomized, double-blind, placebo-controlled Vitamin D Assessment study. Pain. 2018 Jun;159(6):1074-1082.

Vitamin D and calcium

No evidence of an effect on bone mineral density during androgen deprivation therapy among people with prostate cancer or among adolescents with acute lymphoblastic leukemia treated with vitamin D and calcium in several clinical trials

• No evidence of an effect on loss of bone mineral density during androgen deprivation therapy among men with prostate cancer treated the doses commonly recommended—500-1,000 mg calcium and 200-500 IU vitamin D per day—compared to no vitamin D, no calcium, or neither, in a review of 12 clinical trials. Study authors’ note: “high levels of dietary calcium and calcium supplement use are associated with higher risks for cardiovascular disease and advanced prostate cancer,” and so higher supplementation cannot currently be recommended for men in treatment for prostate cancer¹⁷⁸Datta M, Schwartz GG. Calcium and vitamin D supplementation during androgen deprivation therapy for prostate cancer: a critical review. Oncologist. 2012;17(9):1171-9.
• No evidence of an effect on bone density among adolescents with acute lymphoblastic leukemia treated with intermittent high-dose vitamin D3 and 1,000mg daily oral calcium citrate compared to placebo in a small RCT¹⁷⁹Orgel E, Mueske NM et al. A randomized controlled trial testing an adherence-optimized Vitamin D regimen to mitigate bone change in adolescents being treated for acute lymphoblastic leukemia. Leukemia and Lymphoma. 2017 Oct;58(10):2370-2378.

Weak evidence of only slight decline in bone mineral density during conventional or hypofractionated radiation therapy among people with prostate cancer treated with luteinizing hormone-releasing hormone agonist, calcium, and vitamin D3

• Slight (3.2%) declines in bone mineral density at 30 months, with no decline in bone mineral density category in 83% of people, during conventional or hypofractionated radiation therapy among people with localized high-risk prostate cancer treated with 28 months of luteinizing hormone-releasing hormone agonist, 500 mg calcium, and 400 IU vitamin D3 twice a day compared to baseline in an uncontrolled analysisan analysis in which a therapy is used, but without a comparison group against which to judge outcomes of a mid-sized RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects;¹⁸⁰Khriguian J, Tsui JMG et al. The clinical significance of bone mineral density changes following long-term androgen deprivation therapy in localized prostate cancer patients. Journal of Urology. 2021 Jun;205(6):1648-1654. people treated with hormonal therapy for prostate cancer, such as in this study, are at great risk for bone loss, osteoporosis, and bone fractures¹⁸¹Suarez-Almazor ME, Pundole X et al. Association of bone mineral density testing with risk of major osteoporotic fractures among older men receiving androgen deprivation therapy to treat localized or regional prostate cancer. JAMA Network Open. 2022 Apr 1;5(4):e225432; Hormone Therapy for Prostate Cancer. What are the side effects of hormone therapy for prostate cancer? National Cancer Institute. February 22, 2021. Viewed July 20, 2022.

Good evidence of lower incidence of vertebral fractures but no evidence of an effect on incidence of hip fracture among postmenopausal women treated with calcium plus vitamin D

• Lower incidence of vertebral fractures but no evidence of an effect on incidence of hip fracture among postmenopausal women treated with calcium plus vitamin D compared to placebo in a very large RCT¹⁸²Cauley JA, Chlebowski RT et al. Calcium plus vitamin D supplementation and health outcomes five years after active intervention ended: the Women’s Health Initiative. Journal of Women’s Health. 2013 Nov;22(11):915-29.

Vitamin C and vitamin D supplements: preliminary evidence of lower rates of fungal infection, hemorrhage, or macrophage activation syndrome among people with acute myeloid leukemia treated with supplemental vitamin C and vitamin D

• Lower rates of fungal infection, hemorrhage, or macrophage activation syndrome among those treated with supplemental vitamin C and vitamin D from day 10 of chemotherapy until hematologic recovery from induction and consolidation compared to no supplementation in a mid-sized observationala type of study in which individuals are observed or certain outcomes are measured, but no attempt is made to affect the outcome (for example, no treatment is given); an example is a study that records people’s diets, but doesn’t try to alter their diets, and looks for patterns of disease or other outcomes related to different foods study¹⁸³Mouchel PL, Bérard E et al. Vitamin C and D supplementation in acute myeloid leukemia. Blood Advances. 2023 Sep 6:bloodadvances.2023010559.

Vitamin D and omega-3 fatty acids: no evidence of an effect on mood scores, risk of depression incidence or recurrence, or clinically relevant depressive symptoms among people without depression treated with vitamin D and fish oil in a very large study

• No evidence of an effect on mood scores, risk of depression incidence or recurrence, or clinically relevant depressive symptoms over more than 5 years among people without depression treated with 2000 IU cholecalciferol and fish oil per day compared to placebo in a very large RCT¹⁸⁴Okereke OI, Reynolds CF 3rd et al. Effect of long-term vitamin D3 supplementation vs placebo on risk of depression or clinically relevant depressive symptoms and on change in mood scores: a randomized clinical trial. Journal of the American Medical Association. 2020 Aug 4;324(5):471-480.

Vitamin D with outdoor walking, light exposure, and several other vitamins: preliminary evidence of better mood and less depression among women with symptoms of mild to moderate depression treated with a brisk 20-minute outdoor walk at target heart rate of 60% of maximum heart rate, increased light exposure throughout the day, and a vitamin regimen

• Higher measures of overall mood, self-esteem, and general sense of well-being and fewer symptoms on two measures of depression among women with symptoms of mild to moderate depression not taking any mood-altering medication and treated with a brisk 20-minute outdoor walk, increased light exposure throughout the day, and a vitamin regimen of vitamin B1 (thiamine), vitamin B6 (pyroxidine), vitamin B2 (riboflavin), folic acid, selenium, and 400 IU vitamin D compared to a placebo vitamin in a mid-sized RCT¹⁸⁵Brown MA, Goldstein-Shirley J, Robinson J, Casey S. The effects of a multi-modal intervention trial of light, exercise, and vitamins on women’s mood. Women Health. 2001;34(3):93-112.

Vitamin D and vitamin K: preliminary evidence of better markers of bone metabolism during chemotherapy among children with acute lymphoblastic leukemia treated with vitamin K2 and vitamin D3

• Better markers of bone metabolism during chemotherapy among children with acute lymphoblastic leukemia treated with 100 mcg vitamin K2 (menaquinone-7) and 10 mcg vitamin D3 (calcitriol) compared to chemotherapy alone in a small RCT¹⁸⁶Solmaz I, Ozdemir MA et al. Effect of vitamin K2 and vitamin D3 on bone mineral density in children with acute lymphoblastic leukemia: a prospective cohort study. Journal of Pediatric Endocrinology & Metabolism. 2021 Feb 25;34(4):441-447.

DiVFuSS formulation of vitamins C, D₃, and E (d-α tocopherol), zinc oxide, eicosapentaenoic acid, docosahexaenoic acid, α-lipoic acid (racemic mixture), coenzyme Q10, mixed tocotrienols/tocopherols, zeaxanthin, lutein, benfotiamine, N-acetyl cysteine, grape seed extract, resveratrol, turmeric root extract, green tea leaf, and Pycnogenol: preliminary evidence of less diabetic peripheral neuropathy among people treated with DiVFuSS formulation

• Less diabetic peripheral neuropathy among people treated with DiVFuSS formulation for 6 months compared to placebo in a small RCT¹⁸⁷Chous AP, Richer SP, Gerson JD, Kowluru RA. The Diabetes Visual Function Supplement Study (DiVFuSS). British Journal of Ophthalmology. 2016 Feb;100(2):227-34.

QR-333, a topical compound containing quercetin, ascorbyl palmitate, and vitamin D₃: preliminary evidence of less severe numbness, jolting pain, and irritation among people with diabetic peripheral neuropathy treated with QR-333

• Less severe numbness, jolting pain, and irritation among people with diabetic peripheral neuropathy treated with QR-333 3 times daily for 4 weeks compared to placebo in a small RCT¹⁸⁸Valensi P, Le Devehat C et al. A multicenter, double-blind, safety study of QR-333 for the treatment of symptomatic diabetic peripheral neuropathy. A preliminary report. Journal of Diabetes Complications. 2005 Sep-Oct;19(5):247-53.

Vitamin D levels

Weak evidence of lower risk of cancer among people with higher 25(OH)D levels

• A weak trendan apparent change due to a therapy, close to but not achieving full statistical significance (this is the CancerChoices definition; other researchers and studies may define this differently toward lower risk of cancer among people with higher 25(OH)D levels compared to lower levels, and a 7% lower risk with each 8 ng/mL (20 nmol/L) increase of 25(OH)D levels, in a large meta-analysisa statistical analysis that combines the results of two or more research studies; the results of smaller research studies addressing the same or similar questions can be analyzed as though they are one bigger, more powerful study of 8 observationala type of study in which individuals are observed or certain outcomes are measured, but no attempt is made to affect the outcome (for example, no treatment is given); an example is a study that records people’s diets, but doesn’t try to alter their diets, and looks for patterns of disease or other outcomes related to different foods studies¹⁸⁹Han J, Guo X et al. 25-hydroxyvitamin D and total cancer incidence and mortality: a meta-analysis of prospective cohort studies. Nutrients. 2019 Sep 26;11(10):2295.

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

• Lower cancer mortality among people without cancer at baseline with higher 25(OH)D levels compared to lower levels, and 2% lower mortality with each 8 ng/mL (20 nmol/L) increase of 25(OH)D levels, in a very large meta-analysis of 16 observational studies¹⁹⁰Han J, Guo X et al. 25-hydroxyvitamin D and total cancer incidence and mortality: a meta-analysis of prospective cohort studies. Nutrients. 2019 Sep 26;11(10):2295.

Vitamin D intake

Strong evidence of slightly lower cancer mortality among people without cancer at baseline taking vitamin D supplements

• 15% lower cancer mortality among people without cancer at baseline taking vitamin D supplements compared to no supplements in a large meta-analysis of 50 RCTsrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects¹⁹¹Zhang Yu, Fang F et al. Association between vitamin D supplementation and mortality: systematic review and meta-analysis. British Medical Journal. 2019 Aug 12;366:l4673.
• Slightly lower cancer mortality but no evidence of lower risk of cancer among people without cancer at baseline taking vitamin D supplements compared to placebo in a large meta-analysis of 10 RCTs¹⁹²Zhang X, Niu W. Meta-analysis of randomized controlled trials on vitamin D supplement and cancer incidence and mortality. Bioscience Reports. 2019 Nov 29;39(11).
• Slightly lower cancer mortality (5 studies), but no evidence of an effect on cancer incidence (10 studies) among people without cancer at baseline taking supplements and attaining 25(OH)D levels of 22-54 ng/mL (54–135 of  nmol/L) compared to controls not taking supplements, with effects from daily dosing but not from infrequent bolus dosing in meta-analyses of RCTs¹⁹³Keum N, Lee DH, Greenwood DC, Manson JE, Giovannucci E. Vitamin D supplementation and total cancer incidence and mortality: a meta-analysis of randomized controlled trials. Annals of Oncology. 2019 May 1;30(5):733-743.
• A weak trend toward lower cancer mortality after the study period ended among people without cancer at baseline taking vitamin D supplements, but otherwise no evidence of an effect of supplementation on cancer mortality in a large meta-analysis of 30 RCTs¹⁹⁴Goulão B, Stewart F, Ford JA, MacLennan G, Avenell A. Cancer and vitamin D supplementation: a systematic review and meta-analysis. American Journal of Clinical Nutrition. 2018 Apr 1;107(4):652-663.
• Slightly lower cancer mortality but no evidence of an effect on cancer risk among people without cancer at baseline taking vitamin D3 compared to controls in a large meta-analysis of 56 RCTs¹⁹⁵Bjelakovic G, Gluud LL et al. Vitamin D supplementation for prevention of mortality in adults. Cochrane Database of Systematic Reviews. 2014 Jan 10;(1):CD007470.
• A weak trend toward lower cancer mortality, with larger effects at longer latencies, but no evidence of an effect on risk of invasive cancer, among people without cancer at baseline taking vitamin D supplements compared to no supplements in a very large RCT¹⁹⁶Manson JE, Bassuk SS, Buring JE; VITAL Research Group. Principal results of the VITamin D and OmegA-3 TriaL (VITAL) and updated meta-analyses of relevant vitamin D trials. Journal of Steroid Biochemistry and Molecular Biology. 2020 Apr;198:105522.

Modest evidence of lower risk of cancer among healthy adults aged 70 years or older taking vitamin D supplements

• 26% lower risk of cancer as a whole among healthy community-dwelling adults aged 70 years or older taking 2000 IU supplemental vitamin D3 per day compared to placebo in a large RCT; even greater reductions were found when vitamin D was combined with “a simple home strength exercise program (SHEP)” (44% lower risk), omega-3 fatty acids (47% lower risk), or both SHEP and omega-3s (61% lower risk)¹⁹⁷Bischoff-Ferrari HA, Willett WC et al. Combined vitamin D, omega-3 fatty acids, and a simple home exercise program may reduce cancer risk among active adults aged 70 and older: a randomized clinical trial. Frontiers in Aging. 2022 Apr 25;3.

• Lower risk of metastatic or fatal cancer among people without cancer at baseline treated with vitamin D3, with effects mostly among people with body mass index (BMI) below 25 and no evidence of an effect among people with higher BMI in a very large RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects¹⁹⁸Chandler PD, Chen WY et al. Effect of vitamin D3 supplements on development of advanced cancer: a secondary analysis of the VITAL randomized clinical trial. Journal of the American Medical Association Network Open. 2020 Nov 2;3(11):e2025850.

Vitamin D levels

Recurrence: good evidence of lower risk of recurrence among people with breast cancer with higher 25(OH)D levels at diagnosis

• Substantially lower risk of recurrence (better disease-free survivalthe time during and after successful treatment of a disease during which there are no signs and symptoms of the disease that was treated; this is the same as recurrence-free survival) among women with breast cancer with the highest 25(OH)D levels compared to the lowest in a meta-analysisa statistical analysis that combines the results of two or more research studies; the results of smaller research studies addressing the same or similar questions can be analyzed as though they are one bigger, more powerful study of 12 observationala type of study in which individuals are observed or certain outcomes are measured, but no attempt is made to affect the outcome (for example, no treatment is given); an example is a study that records people’s diets, but doesn’t try to alter their diets, and looks for patterns of disease or other outcomes related to different foods studies¹⁹⁹Li C, Li H, Zhong H, Li X. Association of 25-hydroxyvitamin D level with survival outcomes in female breast cancer patients: a meta-analysis. Journal of Steroid Biochemistry and Molecular Biology. 2021 Sep;212:105947.
• 58% lower risk of recurrence (better disease-free survival) among people with breast cancer with the highest 25(OH)D levels at diagnosis compared to the lowest in a meta-analysis of 4 studies²⁰⁰Li M, Chen P et al. Review: the impacts of circulating 25-hydroxyvitamin D levels on cancer patient outcomes: a systematic review and meta-analysis. Journal of Clinical Endocrinology and Metabolism. 2014 Jul;99(7):2327-36.
• 21% lower risk of recurrence and 18% lower risk of invasive disease recurrence across almost 10 years among people with breast cancer with 25(OH)D levels of 30 ng/ml or higher compared to less than 20 ng/ml at the time of diagnosis in a large observational study²⁰¹Yao S, Sheng H et al. Clinically sufficient vitamin D levels at breast cancer diagnosis and survival outcomes in a prospective cohort of 3,995 patients after a median follow-up of 10 years. Poster presentation at the ASCO 2021 Annual Meeting. Viewed June 15, 2021.

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

• A weak trendan apparent change due to a therapy, close to but not achieving full statistical significance (this is the CancerChoices definition; other researchers and studies may define this differently toward slightly lower risk of breast cancer among people with the highest 25(OH)D levels compared to the lowest in a large meta-analysis of 30 observational studies²⁰²Kim Y, Je Y. Vitamin D intake, blood 25(OH)D levels, and breast cancer risk or mortality: a meta-analysis. British Journal of Cancer. 2014 May 27;110(11):2772-84.
• Almost double the risk of breast cancer among women with 25(OH)D levels less than 10 ng/mL compared to higher levels in a meta-analysis of 22 observational studies²⁰³Hossain S, Beydoun MA et al. Vitamin D and breast cancer: a systematic review and meta-analysis of observational studies. Clinical Nutrition ESPEN. 2019 Apr;30:170-184.
• Lower risk of breast cancer among people with higher 25(OH)D levels compared to lower levels, especially among premenopausal women, in a meta-analysis of 68 observational studies²⁰⁴Estébanez N, Gómez-Acebo I, Palazuelos C, Llorca J, Dierssen-Sotos T. Vitamin D exposure and risk of breast cancer: a meta-analysis. Scientific Reports. 2018 Jun 13;8(1):9039.
• 6% lower risk of breast cancer with each 2 ng/mL (5 nmol/L) increase in blood vitamin D levels in a meta-analysis of 50 observational studies²⁰⁵Song D, Deng Y et al. Vitamin D intake, blood vitamin D levels, and the risk of breast cancer: a dose-response meta-analysis of observational studies. Aging (Albany NY). 2019 Dec 28;11(24):12708-12732.
• Higher risk of breast cancer among people with 25(OH)D levels below either 20 ng/mL or 30 ng/mL compared to higher levels in a meta-analysis of 25 observational studies²⁰⁶Voutsadakis IA. Vitamin D baseline levels at diagnosis of breast cancer: a systematic review and meta-analysis. Hematology/Oncology and Stem Cell Therapy. 2021 Mar;14(1):16-26.
• Substantially lower risk of breast cancer among premenopausal women with the highest 25(OH)D levels compared to the lowest, but no evidence of an effect among postmenopausal women in a mid-sized observational study²⁰⁷Jamshidinaeini Y, Akbari ME, Abdollahi M, Ajami M, Davoodi SH. Vitamin D status and risk of breast cancer in Iranian women: a case-control study. Journal of the American College of Nutrition. 2016 Sep-Oct;35(7):639-646.
• More than double the risk of breast cancer among women with 25(OH)D levels less than 20ng/mL compared to higher levels in a mid-sized observational study²⁰⁸Sofi NY, Jain M et al. Reproductive factors, nutritional status and serum 25(OH)D levels in women with breast cancer: a case control study. Journal of Steroid Biochemistry and Molecular Biology. 2018 Jan;175:200-204.

Vitamin D intake

Recurrence: modest evidence of moderately lower risk of recurrence among people taking vitamin D supplements after a diagnosis of ER positive but not ER negative breast cancer

• Moderately lower risk of recurrence among people taking vitamin D supplements after a diagnosis of ER positive but not ER negative breast cancer compared to no vitamin D in a large meta-analysis of 4 observational studies²⁰⁹Poole EM, Shu X et al. Postdiagnosis supplement use and breast cancer prognosis in the After Breast Cancer Pooling Project. Breast Cancer Research and Treatment. 2013 Jun;139(2):529-37.

Cancer diagnosis: preliminary evidence of slightly lower risk of breast cancer among people with higher vitamin D intake

• A weak trend toward slightly lower risk of breast cancer among people with the highest vitamin D intake compared to the lowest in a large meta-analysis of 30 observational studies²¹⁰Kim Y, Je Y. Vitamin D intake, blood 25(OH)D levels, and breast cancer risk or mortality: a meta-analysis. British Journal of Cancer. 2014 May 27;110(11):2772-84.
• Slightly lower risk of breast cancer among women with each 100 IU vitamin D per day increase in intake, either from supplements alone or supplements and diet, in a meta-analysis of 22 observational studies²¹¹Hossain S, Beydoun MA et al. Vitamin D and breast cancer: a systematic review and meta-analysis of observational studies. Clinical Nutrition ESPEN. 2019 Apr;30:170-184.
• A weak trend toward lower risk in cohort studies but no evidence of an effect in case-control studies on risk of breast cancer with an increase of 400 IU vitamin D per day in a meta-analysis of 20 observational studies²¹²Song D, Deng Y et al. Vitamin D intake, blood vitamin D levels, and the risk of breast cancer: a dose-response meta-analysis of observational studies. Aging (Albany NY). 2019 Dec 28;11(24):12708-12732.

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

• Substantially lower risk of colorectal cancer among people with higher 25(OH)D levels compared to lower levels, with higher effects among women compared to men, among people with higher intake of calcium, and among European and American populations compared to Asian populations, in a very large meta-analysisa statistical analysis that combines the results of two or more research studies; the results of smaller research studies addressing the same or similar questions can be analyzed as though they are one bigger, more powerful study of 30 observationala type of study in which individuals are observed or certain outcomes are measured, but no attempt is made to affect the outcome (for example, no treatment is given); an example is a study that records people’s diets, but doesn’t try to alter their diets, and looks for patterns of disease or other outcomes related to different foods studies²¹³Huang D, Lei S et al. Additively protective effects of vitamin D and calcium against colorectal adenoma incidence, malignant transformation and progression: a systematic review and meta-analysis. Clinical Nutrition. 2020 Aug;39(8):2525-2538.
• Moderately lower colorectal cancer-specific mortality among people without cancer at baseline with higher 25(OH)D levels compared to lower levels in a meta-analysis of 11 observational studies²¹⁴Huang D, Lei S et al. Additively protective effects of vitamin D and calcium against colorectal adenoma incidence, malignant transformation and progression: a systematic review and meta-analysis. Clinical Nutrition. 2020 Aug;39(8):2525-2538.
• 31% higher risk of colorectal cancer among people with 25(OH)D levels less than 12 ng/mL (30 nmol/L) compared to levels between 20 and 25 ng/mL (50 and 62.5 nmol/L) in a large meta-analysis of 17 observational studies²¹⁵McCullough ML, Zoltick ES et al. Circulating vitamin D and colorectal cancer risk: an international pooling project of 17 cohorts. JNCI: Journal of the National Cancer Institute. 2019 Feb 1;111(2):158-169.
• 19% lower risk of colorectal cancer among people with 25(OH)D levels between 75 and 87.5 nmol/L compared to levels between 30 and 35 ng/mL (75 and 87.5 nmol/L) compared to levels between 20 and 25 ng/mL (50 and 62.5 nmol/L), and 27% lower risk with levels between 35 and 40 ng/mL (87.5 and 100 nmol/L), but no further benefit at higher levels in a large meta-analysis of 17 observational studies²¹⁶McCullough ML, Zoltick ES et al. Circulating vitamin D and colorectal cancer risk: an international pooling project of 17 cohorts. JNCI: Journal of the National Cancer Institute. 2019 Feb 1;111(2):158-169.
• Moderately lower risk of colorectal cancer among people with highest 25(OH)D levels compared to lowest in meta-analyses of 14,²¹⁷Ekmekcioglu C, Haluza D, Kundi M. 25-hydroxyvitamin D status and risk for colorectal cancer and type 2 diabetes mellitus: a systematic review and meta-analysis of epidemiological studies. International Journal of Environmental Research and Public Health. 2017 Jan 28;14(2):127. 15,²¹⁸Garland CF, Gorham ED. Dose-response of serum 25-hydroxyvitamin D in association with risk of colorectal cancer: a meta-analysis. Journal of Steroid Biochemistry and Molecular Biology. 2017 Apr;168:1-8. 9,²¹⁹Ma Y, Zhang P et al. Association between vitamin D and risk of colorectal cancer: a systematic review of prospective studies. Journal of Clinical Oncology. 2011 Oct 1;29(28):3775-82. 8,²²⁰Zhang L, Zou H et al. Association between blood circulating vitamin D and colorectal cancer risk in Asian countries: a systematic review and dose-response meta-analysis. British Medical Journal Open. 2019 Dec 23;9(12):e030513. and 5²²¹Touvier M, Chan DS et al. Meta-analyses of vitamin D intake, 25-hydroxyvitamin D status, vitamin D receptor polymorphisms, and colorectal cancer risk. Cancer Epidemiology, Biomarkers & Prevention. 2011 May;20(5):1003-16. observational studies
• Lower risk of colorectal cancer, with stronger effects for rectal cancer compared to colon cancer, among people with the highest 25(OH)D levels compared to lowest in a meta-analysis of 8 observational studies²²²Lee JE, Li H et al. Circulating levels of vitamin D and colon and rectal cancer: the Physicians’ Health Study and a meta-analysis of prospective studies. Cancer Prevention Research (Philadelphia). 2011 May;4(5):735-43.
• 20% lower risk of colorectal adenomas among people with higher 25(OH)D levels compared to lower levels in a meta-analysis of 22 observational studies²²³Huang D, Lei S et al. Additively protective effects of vitamin D and calcium against colorectal adenoma incidence, malignant transformation and progression: a systematic review and meta-analysis. Clinical Nutrition. 2020 Aug;39(8):2525-2538.

Vitamin D intake: good evidence of lower risk of colorectal cancer among people with higher total vitamin D intake

• Moderately lower risk of colorectal cancer among people with higher total vitamin D intake (16 studies) compared to lower intake, and slightly lower risk with higher dietary intake (34 studies), or supplement intake (16 studies) compared to lower intake in a very large meta-analysis of studies²²⁴Huang D, Lei S et al. Additively protective effects of vitamin D and calcium against colorectal adenoma incidence, malignant transformation and progression: a systematic review and meta-analysis. Clinical Nutrition. 2020 Aug;39(8):2525-2538.
• Lower risk of colorectal adenomas among people with higher total vitamin D intake compared to lower intake (10 studies), but not dietary intake alone (10 studies) nor supplement intake alone (5 studies) in a meta-analysis of studies²²⁵Huang D, Lei S et al. Additively protective effects of vitamin D and calcium against colorectal adenoma incidence, malignant transformation and progression: a systematic review and meta-analysis. Clinical Nutrition. 2020 Aug;39(8):2525-2538.
• 25% lower risk of colorectal cancer among people with the highest total vitamin D intake compared to the lowest in a meta-analysis of 5 meta-analyses of case-control observational studies mostly of good quality, but no evidence of an effect in a separate meta-analysis of prospective observational studies²²⁶Boughanem H, Canudas S et al. Vitamin D intake and the risk of colorectal cancer: an updated meta-analysis and systematic review of case-control and prospective cohort studies. Cancers (Basel). 2021 Jun 4;13(11):2814.
• Slightly lower risk of colorectal cancer among people with highest vitamin D intake compared to the lowest in a very large meta-analysis of observational studies²²⁷Ma Y, Zhang P et al. Association between vitamin D and risk of colorectal cancer: a systematic review of prospective studies. Journal of Clinical Oncology. 2011 Oct 1;29(28):3775-82.

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

• Slightly lower risk of CRC as a whole with each increase of 100 IU dietary vitamin D intake per day (10 studies), but no significant effect among studies investigating only colon (8 studies) or rectal (6 studies) cancer separately in a meta-analysis of observational studies²²⁸Touvier M, Chan DS et al. Meta-analyses of vitamin D intake, 25-hydroxyvitamin D status, vitamin D receptor polymorphisms, and colorectal cancer risk. Cancer Epidemiology, Biomarkers & Prevention. 2011 May;20(5):1003-16.

Vitamin D from supplements only

Good evidence of slightly lower risk of colorectal cancer among people taking vitamin D supplements

• Slightly lower risk of colorectal cancer among people taking vitamin D supplements compared to no supplements in a very large meta-analysis of 21 observational studies²²⁹Xu Y, Qian M et al. The effect of vitamin D on the occurrence and development of colorectal cancer: a systematic review and meta-analysis. International Journal of Colorectal Disease. 2021 Jul;36(7):1329-1344.
• A weak trendan apparent change due to a therapy, close to but not achieving full statistical significance (this is the CancerChoices definition; other researchers and studies may define this differently toward slightly lower risk of colorectal cancer among people taking vitamin D compared to no use (5 studies) but no evidence of an effect on risk of colorectal cancer among people taking higher levels of vitamin D compared to lower levels (4 studies), although a lower risk for each 100 mg increase in vitamin D per day (3 studies) in meta-analyses of observational studies²³⁰Heine-Bröring RC, Winkels RM et al. Dietary supplement use and colorectal cancer risk: a systematic review and meta-analyses of prospective cohort studies. International  Journal of Cancer. 2015 May 15;136(10):2388-401.

No evidence of an effect on risk of adenoma after colorectal adenoma surgery among people treated with vitamin D3 in a large study

• No evidence of an effect on risk of adenoma after colorectal adenoma surgery among people age 45–75 years with vitamin D levels between 12 and 90 ng/ml treated with 1000 IU vitamin D3 per day compared to no vitamin D3 in a large RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects²³¹Calderwood AH, Baron JA et al. No evidence for posttreatment effects of vitamin D and calcium supplementation on risk of colorectal adenomas in a randomized trial. Cancer Prevention Research (Philadelphia, Pa.). 2019 May;12(5):295-304.

Vitamin D levels: good evidence of higher risk of liver cancer among people with low levels of vitamin D

• More than double the risk of liver cancer among people with vitamin D deficiency (undefined) compared to sufficiency (undefined) in a large meta-analysisa statistical analysis that combines the results of two or more research studies; the results of smaller research studies addressing the same or similar questions can be analyzed as though they are one bigger, more powerful study of 11 observationala type of study in which individuals are observed or certain outcomes are measured, but no attempt is made to affect the outcome (for example, no treatment is given); an example is a study that records people’s diets, but doesn’t try to alter their diets, and looks for patterns of disease or other outcomes related to different foods studies²³²Yi Z, Wang L, Tu X. Effect of vitamin D deficiency on liver cancer risk: a systematic review and meta-analysis. Asian Pacific Journal of Cancer Prevention. 2021 Apr 1;22(4):991-997.
• 22% lower risk of liver cancer among people with highest 25(OH)D levels compared to the lowest, with an 8% lower risk with each 4 ng/mL (10 nmol/L) increase in 25(OH)D levels in a large meta-analysis of 6 observational studies²³³Guo XF, Zhao T, Han JM, Li S, Li D. Vitamin D and liver cancer risk: a meta-analysis of prospective studies. Asia Pacific Journal of Clinical Nutrition. 2020;29(1):175-182.
• 47% lower risk of liver cancer among people with the highest 25(OH)D levels compared to lowest in a meta-analysis of 6 observational studies²³⁴Zhang Y, Jiang X et al. Serum vitamin D levels and risk of liver cancer: a systematic review and dose-response meta-analysis of cohort studies. Nutrition and Cancer. 2021;73(8):1-9.

Vitamin D intake: preliminary evidence of lower risk of recurrence after surgery among people with esophageal cancer taking vitamin D supplements

• Lower risk of recurrence (better disease-free survival) at 24 months after surgery among people with esophageal cancer taking 200–400 IU vitamin D supplements daily compared to no supplements in a mid-sized observational study²³⁵Wang L, Wang C, Wang J, Huang X, Cheng Y. Longitudinal, observational study on associations between postoperative nutritional vitamin D supplementation and clinical outcomes in esophageal cancer patients undergoing esophagectomy. Scientific Reports. 2016 Dec 13;6:38962.

• Lower risk of recurrence of grade 1–3 disease among women with grade 2 or 3 cervical intraepithelial neoplasia treated with 50,000 IU vitamin D3 every 2 weeks for 6 months compared to placebo, with most of the effect relating to grade 1 disease in a small RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects²³⁶Vahedpoor Z, Mahmoodi S et al. Long-term vitamin D supplementation and the effects on recurrence and metabolic status of cervical intraepithelial neoplasia grade 2 or 3: a randomized, double-blind, placebo-controlled trial. Annals of Nutrition and Metabolism. 2018;72(2):151-160.

Vitamin D levels: good evidence of lower risk of head and neck cancer among people with high 25(OH)D levels

• Lower risk of head and neck cancer among people with high 25(OH)D levels compared to lower levels in a large meta-analysisa statistical analysis that combines the results of two or more research studies; the results of smaller research studies addressing the same or similar questions can be analyzed as though they are one bigger, more powerful study of 16 observationala type of study in which individuals are observed or certain outcomes are measured, but no attempt is made to affect the outcome (for example, no treatment is given); an example is a study that records people’s diets, but doesn’t try to alter their diets, and looks for patterns of disease or other outcomes related to different foods studies²³⁷Pu Y, Zhu G et al. Association between vitamin D exposure and head and neck cancer: a systematic review with meta-analysis. Frontiers in Immunology. 2021 Feb 23;12:627226.

Vitamin D intake

Recurrence: preliminary evidence of lower risk of recurrence among people with head and neck cancer with higher total (diet and supplement) intake of vitamin D

• 53% lower risk of recurrence at 5 years among people with head and neck cancer with total (diet and supplement) intake of vitamin D of 675 IU per day or higher compared to less than 200 IU, but no evidence of effects for vitamin D from diet alone or from supplements alone, in a mid-sized observational study²³⁸Yokosawa EB, Arthur AE et al. Vitamin D intake and survival and recurrence in head and neck cancer patients. Laryngoscope. 2018 Nov;128(11):E371-E376.

Cancer risk: good evidence of lower risk of head and neck cancer among people with high intake of vitamin D in their diet

• Lower risk of head and neck cancer among people with high intake of vitamin D in their diet compared to “a regular diet” in a large meta-analysis of 16 observational studies²³⁹Pu Y, Zhu G et al. Association between vitamin D exposure and head and neck cancer: a systematic review with meta-analysis. Frontiers in Immunology. 2021 Feb 23;12:627226.

Vitamin D levels: modest evidence of lower risk of renal cell carcinoma among people, especially women, with the highest circulating vitamin D levels

• 24% lower risk of renal cell carcinoma among people, especially women, with the highest circulating vitamin D levels compared to the lowest in a meta-analysisa statistical analysis that combines the results of two or more research studies; the results of smaller research studies addressing the same or similar questions can be analyzed as though they are one bigger, more powerful study of 4 observationala type of study in which individuals are observed or certain outcomes are measured, but no attempt is made to affect the outcome (for example, no treatment is given); an example is a study that records people’s diets, but doesn’t try to alter their diets, and looks for patterns of disease or other outcomes related to different foods studies²⁴⁰Wu J, Yang N, Yuan M. Dietary and circulating vitamin D and risk of renal cell carcinoma: a meta-analysis of observational studies. International Brazilian Journal of Urology. 2021 Jul-Aug;47(4):733-744.

Vitamin D intake: modest evidence of lower risk of renal cell carcinoma among people, especially women, with the highest dietary vitamin D intake

• 14% lower risk of renal cell carcinoma among people, especially women, with the highest dietary vitamin D intake compared to the lowest in a meta-analysis of 6 observational studies²⁴¹Wu J, Yang N, Yuan M. Dietary and circulating vitamin D and risk of renal cell carcinoma: a meta-analysis of observational studies. International Brazilian Journal of Urology. 2021 Jul-Aug;47(4):733-744.

Vitamin D levels

Good evidence of lower risk of lung cancer among people with higher 25(OH)D levels, although very high levels—above about 85 nmol/L—are linked to increased risk

• A nonlinear effect, with a suggestion of higher risk of lung cancer among people with 25(OH)D levels either below about 18 ng/mL (45 nmol/L) or above about 34 ng/mL (85 nmol/L) compared to mid-range levels in a meta-analysisa statistical analysis that combines the results of two or more research studies; the results of smaller research studies addressing the same or similar questions can be analyzed as though they are one bigger, more powerful study of 12 observationala type of study in which individuals are observed or certain outcomes are measured, but no attempt is made to affect the outcome (for example, no treatment is given); an example is a study that records people’s diets, but doesn’t try to alter their diets, and looks for patterns of disease or other outcomes related to different foods studies²⁴²Wei H, Jing H, Wei Q, Wei G, Heng Z. Associations of the risk of lung cancer with serum 25-hydroxyvitamin D level and dietary vitamin D intake: a dose-response PRISMA meta-analysis. Medicine (Baltimore). 2018 Sep;97(37):e12282.
• Lower risk of lung cancer among people with higher 25(OH)D levels, with a trend toward lower risk  between about 12 and 24 ng/mL (30 and 60 nmol/L) compared to the lower or higher levels, and an 8% lower risk with each 4 ng/mL (10 nmol/L) increase, in a meta-analysis of 9 observational studies²⁴³Feng Q, Zhang H, Dong Z, Zhou Y, Ma J. Circulating 25-hydroxyvitamin D and lung cancer risk and survival: a dose-response meta-analysis of prospective cohort studies. Medicine (Baltimore). 2017 Nov;96(45):e8613.

Modest evidence of lower lung-cancer mortality among people without cancer at baseline with higher 25(OH)D levels; see also indications that very high levels may increase mortality in Safety and precautions ›

• Lower risk of lung cancer-specific mortality among people without cancer at baseline with higher 25(OH)D levels compared to lower levels, and 7% lower risk with each 4 ng/mL (10 nmol/L) increase of 25(OH)D levels, in a meta-analysis of 4 observational studies²⁴⁴Feng Q, Zhang H, Dong Z, Zhou Y, Ma J. Circulating 25-hydroxyvitamin D and lung cancer risk and survival: a dose-response meta-analysis of prospective cohort studies. Medicine (Baltimore). 2017 Nov;96(45):e8613.

Vitamin D intake: modest evidence of slightly lower risk of lung cancer among people with the highest vitamin D intake from either diet or supplements

• Slightly lower risk of lung cancer among people with the highest dietary vitamin D intake compared to the lowest in a meta-analysis of 12 observational studies²⁴⁵Wei H, Jing H, Wei Q, Wei G, Heng Z. Associations of the risk of lung cancer with serum 25-hydroxyvitamin D level and dietary vitamin D intake: A dose-response PRISMA meta-analysis. Medicine (Baltimore). 2018 Sep;97(37):e12282.
• Slightly lower risk of lung cancer among people taking vitamin D supplements compared to non-users in a meta-analysis of 6 observational studies²⁴⁶Qian M, Lin J et al. The role of vitamin D intake on the prognosis and incidence of lung cancer: a systematic review and meta-analysis. Journal of Nutritional Science and Vitaminology (Tokyo). 2021;67(5):273-282.

Vitamin D levels

Modest evidence of lower risk of recurrence among people with lymphoma with the highest 25(OH)D levels at diagnosis

• 20% lower risk of recurrence (better disease-free survival) among people with lymphoma with the highest 25(OH)D levels at diagnosis compared to the lowest levels in a meta-analysisa statistical analysis that combines the results of two or more research studies; the results of smaller research studies addressing the same or similar questions can be analyzed as though they are one bigger, more powerful study of 2 observationala type of study in which individuals are observed or certain outcomes are measured, but no attempt is made to affect the outcome (for example, no treatment is given); an example is a study that records people’s diets, but doesn’t try to alter their diets, and looks for patterns of disease or other outcomes related to different foods studies²⁴⁷Li M, Chen P et al. Review: the impacts of circulating 25-hydroxyvitamin D levels on cancer patient outcomes: a systematic review and meta-analysis. Journal of Clinical Endocrinology and Metabolism. 2014 Jul;99(7):2327-36.

No evidence of an effect of 25(OH)D levels on risk of non-Hodgkin lymphoma in a combined analysis of studies

• No evidence of an effect on risk of non-Hodgkin lymphoma among people with 25(OH)D levels less than 20 ng/mL (50 nmol/L) compared to between 20 and 30 ng/mL (50 and 75 nmol/L) in a meta-analysis of 3 observational studies²⁴⁸Park HY, Hong YC, Lee K, Koh J. Vitamin D status and risk of non-Hodgkin lymphoma: an updated meta-analysis. PLoS One. 2019 Apr 29;14(4):e0216284.

Sunlight/ultraviolet radiation (UVR) exposure: modest evidence of lower risk of non-Hodgkin lymphoma among people with high levels of exposure to sunlight/ultraviolet radiation

• 20% lower risk of non-Hodgkin lymphoma among people with high levels of exposure to sunlight/UV radiation compared to low levels in a meta-analysis of 17 observational studies²⁴⁹Park HY, Hong YC, Lee K, Koh J. Vitamin D status and risk of non-Hodgkin lymphoma: an updated meta-analysis. PLoS One. 2019 Apr 29;14(4):e0216284.

Vitamin D intake: no evidence of an effect on risk of non-Hodgkin lymphoma among people with higher levels of dietary vitamin D intake in a combined analysis of 9 studies

• No evidence of an effect on risk of non-Hodgkin lymphoma among people with dietary vitamin D intake of 200 IU or more per day compared to less in a meta-analysis of 9 observational studies²⁵⁰Park HY, Hong YC, Lee K, Koh J. Vitamin D status and risk of non-Hodgkin lymphoma: an updated meta-analysis. PLoS One. 2019 Apr 29;14(4):e0216284.

Vitamin D levels

Recurrence: modest evidence of lower risk of melanoma recurrence among people with higher 25(OH)D levels

• Almost 5 times higher risk of recurrence (shorter disease-free survival) at 12 months among people with newly resected stage 2 melanoma with low 25(OH)D levels (below 20 ng/mL from December to July and below 30 ng/mL from August to November) and Breslow score of 3 mm or more compared to those with Breslow score less than 3 mm and/or high levels of 25(OH)D in a mid-sized RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects²⁵¹Johansson H, Spadola G et al. Vitamin D supplementation and disease-free survival in stage ii melanoma: a randomized placebo controlled trial. Nutrients. 2021 Jun 4;13(6):1931.
• Lower risk of recurrence (longer disease-free intervals) a year or more after diagnosis among people with resected stage 2 melanoma treated with bevacizumab with higher vitamin D levels compared to lower levels, but no evidence of an effect among people with stage 3 cancer or not treated with bevacizumab, in a mid-sized observational study²⁵²Lipplaa A, Fernandes R et al. 25-hydroxyvitamin D serum levels in patients with high risk resected melanoma treated in an adjuvant bevacizumab trial. British Journal of Cancer. 2018 Oct;119(7):793-800.

Cancer risk

Modest evidence of a link between vitamin D deficiency and melanoma incidence/stage; also see evidence of a higher risk of skin cancer among people with high levels of vitamin D in Safety and precautions ›

• Higher prevalence of vitamin D deficiency among people with melanoma compared to no melanoma, and higher vitamin D levels among people with Breslow thickness at or below 1 mm compared to higher thickness in a meta-analysisa statistical analysis that combines the results of two or more research studies; the results of smaller research studies addressing the same or similar questions can be analyzed as though they are one bigger, more powerful study of 25 observationala type of study in which individuals are observed or certain outcomes are measured, but no attempt is made to affect the outcome (for example, no treatment is given); an example is a study that records people’s diets, but doesn’t try to alter their diets, and looks for patterns of disease or other outcomes related to different foods studies²⁵³Tsai TY, Kuo CY, Huang YC. The association between serum vitamin D level and risk and prognosis of melanoma: a systematic review and meta-analysis. Journal of the European Academy of Dermatology and Venereology. 2020 Aug;34(8):1722-1729.

Preliminary evidence of higher incidence of greater tumor size at diagnosis and metastasis recurrence among people with Merkel cell carcinoma with low vitamin D levels

• Higher incidence of greater tumor size at diagnosis and metastasis recurrence among people with Merkel cell carcinoma with vitamin D levels below 20 ng/mL (50 nmol/L) within 3 years after diagnosis in a small observational study²⁵⁴Samimi M, Touzé A et al. Vitamin D deficiency is associated with greater tumor size and poorer outcome in Merkel cell carcinoma patients. Journal of the European Academy of Dermatology and Venereology. 2014 Mar;28(3):298-308.

Vitamin D intake: preliminary evidence of lower incidence of past or present melanoma or any type of skin cancer among people regularly using vitamin D supplements

• Lower incidence of past or present melanoma or any type of skin cancer, and no evidence of an effect on photoaging, actinic keratoses, nevi, basal, and squamous cell carcinoma, among people regularly using vitamin D supplements compared to non-users in a mid-sized observational study²⁵⁵Kanasuo E, Siiskonen H, Haimakainen S, Komulainen J, Harvima IT. Regular use of vitamin D supplement is associated with fewer melanoma cases compared to non-use: a cross-sectional study in 498 adult subjects at risk of skin cancers. Melanoma Research. 2023 Apr 1;33(2):126-135.

Vitamin D levels: modest evidence of slightly lower risk of ovarian cancer among people with higher circulating vitamin D levels

• Slightly lower risk of ovarian cancer among people with circulating vitamin D levels of about 16 ng/mL (40 nmol/L) or higher compared to about 8 ng/mL (20 nmol/L) in a meta-analysisa statistical analysis that combines the results of two or more research studies; the results of smaller research studies addressing the same or similar questions can be analyzed as though they are one bigger, more powerful study of 4 observationala type of study in which individuals are observed or certain outcomes are measured, but no attempt is made to affect the outcome (for example, no treatment is given); an example is a study that records people’s diets, but doesn’t try to alter their diets, and looks for patterns of disease or other outcomes related to different foods studies²⁵⁶Liao MQ, Gao XP et al. Effects of dairy products, calcium and vitamin D on ovarian cancer risk: a meta-analysis of twenty-nine epidemiological studies. British Journal of Nutrition. 2020 Nov 28;124(10):1001-1012.

Vitamin D intake

Weak evidence of a lower risk of ovarian cancer among people with higher dietary vitamin D intake

Insufficient evidence of slightly lower risk of ovarian cancer among people with higher vitamin D intake from supplements

• A weak trendan apparent change due to a therapy, close to but not achieving full statistical significance (this is the CancerChoices definition; other researchers and studies may define this differently toward a lower risk of ovarian cancer among people with higher dietary vitamin D intake, but no evidence of an effect from supplement intake, whether with or without calcium, in a very large meta-analysis of 21 observational studies²⁵⁷Xu J, Chen K et al. Association between vitamin D/calcium intake and 25-hydroxyvitamin D and risk of ovarian cancer: a dose-response relationship meta-analysis. European Journal of Clinical Nutrition. 2021 Mar;75(3):417-429.
• Slightly lower risk of ovarian cancer among women with higher dietary vitamin D intake compared to lower levels, especially lower than about 200 IU per day, in a meta-analysis of 4 observational studies²⁵⁸Liao MQ, Gao XP et al. Effects of dairy products, calcium and vitamin D on ovarian cancer risk: a meta-analysis of twenty-nine epidemiological studies. British Journal of Nutrition. 2020 Nov 28;124(10):1001-1012.

Vitamin D levels: no evidence of an effect on risk of pancreatic cancer among people with higher 25(OH)D levels in a combined analysis of studies

• No evidence of an effect on risk of pancreatic cancer among people with higher 25(OH)D levels compared to lower levels in a meta-analysisa statistical analysis that combines the results of two or more research studies; the results of smaller research studies addressing the same or similar questions can be analyzed as though they are one bigger, more powerful study of 5 observationala type of study in which individuals are observed or certain outcomes are measured, but no attempt is made to affect the outcome (for example, no treatment is given); an example is a study that records people’s diets, but doesn’t try to alter their diets, and looks for patterns of disease or other outcomes related to different foods studies²⁵⁹Zhang X, Huang XZ et al. Plasma 25-hydroxyvitamin D levels, vitamin D intake, and pancreatic cancer risk or mortality: a meta-analysis. Oncotarget. 2017 Jun 29;8(38):64395-64406.

Vitamin D intake: insufficient (conflicting) evidence of an effect of vitamin D intake on risk of pancreatic cancer

• 25% lower risk of pancreatic cancer among people with the highest vitamin D intake levels compared to the lowest in a meta-analysis of 3 prospective observational studies;²⁶⁰Liu Y, Wang X, Sun X, Lu S, Liu S. Vitamin intake and pancreatic cancer risk reduction: a meta-analysis of observational studies. Medicine (Baltimore). 2018 Mar;97(13):e0114. also see evidence of higher risk in Safety and precautions ›
• No evidence of an effect on risk of pancreatic cancer among people with higher vitamin D intake compared to lower levels in a meta-analysis of 2 observational studies²⁶¹Zhang X, Huang XZ et al. Plasma 25-hydroxyvitamin D levels, vitamin D intake, and pancreatic cancer risk or mortality: a meta-analysis. Oncotarget. 2017 Jun 29;8(38):64395-64406.

Vitamin D levels: good evidence of higher risk of prostate cancer among men with low 25(OH)D levels

• Lower risk of prostate cancer among men with 25(OH)D levels higher than 15 ng/mL (37 nmol/L) compared to lower levels in an observationala type of analysis in which individuals are observed or certain outcomes are measured, but no attempt is made to affect the outcome (for example, no treatment is given); an example is an analysis that records people’s diets, but doesn’t try to alter their diets, and looks for patterns of disease or other outcomes related to different foods analysis within a very large study²⁶²Kristal AR, Till C et al. Plasma vitamin D and prostate cancer risk: results from the Selenium and Vitamin E Cancer Prevention Trial. Cancer Epidemiology, Biomarkers and Prevention. 2014 Aug;23(8):1494-504.
• Higher risk of prostate cancer among men younger than age 51, but not older men, with 25(OH)D levels below 20 ng/mL (50 nmol/L) compared to higher levels, and higher risk of aggressive prostate cancer among those with the lowest levels in a very large observational study²⁶³Tuohimaa P, Lyakhovich A et al. Vitamin D and prostate cancer. Journal of Steroid Biochemistry and Molecular Biology. 2001 Jan-Mar;76(1-5):125-34.
• A weak trendan apparent change due to a therapy, close to but not achieving full statistical significance (this is the CancerChoices definition; other researchers and studies may define this differently toward higher risk of prostate cancer among people with 25(OH)D levels less than 16 ng/mL (40 nmol/L) compared to 16-24 ng/mL (40–59 nmol/L) in a large observational study²⁶⁴Tuohimaa P, Tenkanen L et al. Both high and low levels of blood vitamin D are associated with a higher prostate cancer risk: a longitudinal, nested case-control study in the Nordic countries. International Journal of Cancer. 2004 Jan 1;108(1):104-8.

Vitamin D intake

Modest evidence of lower risk of aggressive prostate cancer among African-Americans or people with low body mass index taking the highest levels of vitamin D supplements, but not among other people

• 62% lower risk of aggressive prostate cancer among people taking the highest levels of vitamin D supplements compared to the lowest levels, but only among African-Americans and not European-Americans, or among men with low body mass index but not with higher body mass index, in a large observational study²⁶⁵Batai K, Murphy AB et al. Race and BMI modify associations of calcium and vitamin D intake with prostate cancer. BMC Cancer. 2017 Jan 19;17(1):64.

No evidence of an effect at 3 months on free or total PSA among healthy men taking vitamin D in a small study

• No evidence of an effect at 3 months on free or total PSA among healthy men of African-American descent taking 1000, 2000, or 4000 IU vitamin D compared to placebo in a mid-sized RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects²⁶⁶Chandler PD, Giovannucci EL et al. Null association between vitamin D and PSA levels among black men in a vitamin D supplementation trial. Cancer Epidemiology, Biomarkers & Prevention. 2014 Sep;23(9):1944-7.

• 30% higher risk of thyroid cancer among people with vitamin D deficiency (variously defined across studies) compared to sufficiency in a meta-analysisa statistical analysis that combines the results of two or more research studies; the results of smaller research studies addressing the same or similar questions can be analyzed as though they are one bigger, more powerful study of 6 observationala type of study in which individuals are observed or certain outcomes are measured, but no attempt is made to affect the outcome (for example, no treatment is given); an example is a study that records people’s diets, but doesn’t try to alter their diets, and looks for patterns of disease or other outcomes related to different foods studies of high quality²⁶⁷Zhao J, Wang H et al. Vitamin D deficiency as a risk factor for thyroid cancer: a meta-analysis of case-control studies. Nutrition. 2019 Jan;57:5-11.
• Lower 25(OH)D levels among people with thyroid cancer compared to controls in a meta-analysis of 12 observational studies of high quality²⁶⁸Zhao J, Wang H et al. Vitamin D deficiency as a risk factor for thyroid cancer: a meta-analysis of case-control studies. Nutrition. 2019 Jan;57:5-11.
• Higher risk of papillary thyroid cancer among people with the lowest levels of vitamin D compared to the highest, or with vitamin D deficiency (variously defined across studies) compared to sufficiency in a meta-analysis of 11 observational studies²⁶⁹Hu MJ, Zhang Q et al. Association between vitamin D deficiency and risk of thyroid cancer: a case-control study and a meta-analysis. Journal of Endocrinological Investigation. 2018 Oct;41(10):1199-1210.

Vitamin D and omega-3 fatty acids: no evidence of an effect on risk of conventional adenomas and serrated polyps among people treated with vitamin D and fish oil

• No evidence of an effect on risk of conventional adenomas and serrated polyps over an average of about 3 years among people with no history of cancer, 50 years or older for men and 55 years or older for women, treated with 2000 IU vitamin D3 and 1 g marine n-3 fatty acid per day compared with placebo, with a very weak trendan apparent change due to a therapy, close to but not achieving full statistical significance (this is the CancerChoices definition; other researchers and studies may define this differently toward lower risk among people with serum 25(OH)D levels below 30 ng/mL compared to higher levels, in a very large RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects²⁷⁰Song M, Lee IM et al. No association between vitamin D supplementation and risk of colorectal adenomas or serrated polyps in a randomized trial. Clinical Gastroenterology and Hepatology. 2021 Jan;19(1):128-135.e6.

Vitamin D and calcium

Cancer as a whole: good evidence of lower risk of cancer as a whole among postmenopausal women treated with vitamin D and calcium

• Lower risk of cancer as a whole at 1 year and a weak trend toward lower risk at 4 years among healthy postmenopausal women in rural counties and aged 55 years or older treated with 2000 IU vitamin D3 and 1500 mg calcium per day compared to placebos in a very large RCT²⁷¹Lappe J, Watson P et al. Effect of vitamin D and calcium supplementation on cancer incidence in older women: a randomized clinical trial. Journal of the American Medical Association. 2017 Mar 28;317(12):1234-1243.

Blood cancer: good evidence of lower risk of blood cancer (hematologic malignancy) among people treated with calcium and vitamin D supplements

• 20% lower risk of hematologic malignancy (HM) but no evidence of an effect on HM mortality over 10 years among people without HM at baseline treated with calcium and vitamin D supplements compared to no supplements, with lower risks related to lymphoid malignancies, in a very large RCT²⁷²Ammann EM, Drake MT et al. Incidence of hematologic malignancy and cause-specific mortality in the Women’s Health Initiative randomized controlled trial of calcium and vitamin D supplementation. Cancer. 2017 Nov 1;123(21):4168-4177.

Breast cancer: modest evidence of lower risk of breast cancer mortality but no evidence of an effect on risk of invasive breast cancer among postmenopausal women treated with calcium plus vitamin D, but see also an increase in risk among women with higher baseline intake of vitamin D in Safety and precautions ›

• 7% lower risk of breast cancer mortality among postmenopausal women treated with 1000 mg calcium carbonate (400 mg of elemental calcium) and 400 IU of vitamin D3 daily compared to placebo in a very large RCT;²⁷³Thomson CA, Aragaki AK et al. Long-term effect of randomization to calcium and vitamin d supplementation on health in older women: postintervention follow-up of a randomized clinical trial. Annals of Internal Medicine. 2024 Mar 12. also see results from the same study finding higher risk of cardiovascular disease mortality with use of calcium and vitamin D in Safety and precautions ›
• No evidence of an effect on risk of invasive breast cancer overall among postmenopausal women treated with calcium plus vitamin D compared to placebo in a very large RCT²⁷⁴Cauley JA, Chlebowski RT et al. Calcium plus vitamin D supplementation and health outcomes five years after active intervention ended: the Women’s Health Initiative. Journal of Women’s Health. 2013 Nov;22(11):915-29.

Colorectal cancer

Modest evidence of a slightly lower risk of colorectal adenoma recurrence, including advanced adenomas, among people treated with calcium and with higher 25(OH)D levels

• Slightly lower risk of colorectal adenoma recurrence, including advanced adenomas, with each 12 ng/mL increase of 25(OH)D levels among people treated with 3 g calcium carbonate, but no evidence of an effect among people treated with placebo in a large RCT²⁷⁵Grau MV, Baron JA et al. Vitamin D, calcium supplementation, and colorectal adenomas: results of a randomized trial. JNCI: Journal of the National Cancer Institute. 2003;95(23):1765-1771.

Weak evidence of a lower risk of colorectal cancer among women not treated with estrogen, but no evidence of an effect on risk across all women treated with vitamin D and calcium; see also information about an increased risk among women treated with estrogen therapy treated with vitamin D and calcium in Safety and
precautions ›

• No evidence of an effect on risk of colorectal cancer among postmenopausal women treated with calcium plus vitamin D compared to placebo in a very large RCT²⁷⁶Cauley JA, Chlebowski RT et al. Calcium plus vitamin D supplementation and health outcomes five years after active intervention ended: the Women’s Health Initiative. Journal of Women’s Health. 2013 Nov;22(11):915-29.
• A weak trend toward a lower risk of colorectal cancer among women not treated with estrogen therapy treated with 400 IU of vitamin-D3 plus 1000 mg elemental calcium compared to placebo in a secondary analysis of a very large RCT²⁷⁷Ding EL, Mehta S, Fawzi WW, Giovannucci EL. Interaction of estrogen therapy with calcium and vitamin D supplementation on colorectal cancer risk: reanalysis of Women’s Health Initiative randomized trial. International Journal of Cancer. 2008 Apr 15;122(8):1690-4.

Skin cancer

Modest evidence of lower risk of invasive cutaneous squamous cell carcinoma among people with colorectal adenomas treated with vitamin D and calcium

• Lower risk of invasive cutaneous squamous cell carcinoma but not basal cell carcinoma at 8 years among people with colorectal adenomas treated with 1000 IU vitamin D3 and 1200 mg calcium carbonate per day for 3 or 5 years, but not vitamin D alone, compared to placebo in in a secondary analysis of a large RCT²⁷⁸Passarelli MN, Karagas MR et al. Risk of keratinocyte carcinomas with vitamin D and calcium supplementation: a secondary analysis of a randomized clinical trial. American Journal of Clinical Nutrition. 2020 Dec 10;112(6):1532-1539

Good evidence of lower risk of melanoma among postmenopausal women aged 50-79 with a history of non-melanoma skin cancer treated with vitamin D and calcium

No evidence of an effect on risk of melanoma among postmenopausal women aged 50-79 without a history of non-melanoma skin cancer treated with vitamin D and calcium

• Lower risk of melanoma but no evidence of an effect on non-melanoma skin cancer at about 7 years among postmenopausal women aged 50-79 with a history of non-melanoma skin cancer treated with 1,000 mg elemental calcium plus 400 IU vitamin D3 daily compared to placebo, but no evidence of an effect among women without a history of non-melanoma skin cancer, in a subgroup analysis within a very large RCT²⁷⁹Tang JY, Fu T et al. Calcium plus vitamin D supplementation and the risk of nonmelanoma and melanoma skin cancer: post hoc analyses of the women’s health initiative randomized controlled trial. Journal of Clinical Oncology. 2011 Aug 1;29(22):3078-84.

Vitamin D, strength exercise, and omega-3 fatty acids: modest evidence of lower risk of cancer among healthy community-dwelling adults aged 70 years or older  treated with vitamin D in combination with strength exercise, omega-3 fatty acids, or both

• Lower risk of cancer as a whole among healthy community-dwelling adults aged 70 years or older taking 2000 IU supplemental vitamin D3 per day combined with “a simple home strength exercise program (SHEP)” (44% lower risk), omega-3 fatty acids (47% lower risk), or both SHEP and omega-3s (61% lower risk) compared to placebo in a large RCT²⁸⁰Bischoff-Ferrari HA, Willett WC et al. Combined vitamin D, omega-3 fatty acids, and a simple home exercise program may reduce cancer risk among active adults aged 70 and older: a randomized clinical trial. Frontiers in Aging. 2022 Apr 25;3:852643.