Vitamin D and cancer! Does deficiency cause cancer? Do high levels prevent it?
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Short answer: vitamin D does not protect against cancer
The previous version of this article was written in 2018, when the question was genuinely open. Since then, involving tens of thousands of people, randomized trial results have been published —and the picture has largely become clear. The defensible answer today is: Vitamin D supplementation does not reduce the risk of developing cancer. The only weak remaining signal concerns cancer mortality , and that is not established either.
What changed in this update:
- The VITAL trial (25.871 people, 2000 IU daily, 5,3 years): for cancer incidence, no difference —hazard ratio 0,96.
- The D-Health trial (21.315 people, Australia): no difference in cancer incidence; cancer mortality was numerically higher .
- Genetic studies (Mendelian randomization, 31 studies) find no causal relationship. This suggests the association in observational studies most likely reflects reverse causation .
- Guidelines changed: The Endocrine Society’s 2024 guideline recommends against routine vitamin D testing and supplementation in healthy adults .
- In our old text, the SUNSHINE trial was misreported; we correct it. The confirmatory trial, SOLARIS , in 2024 had negative results.
- Vitamin D’s real place in oncology —correcting deficiency before bone-protective medicines—was entirely absent from the earlier article.
What does vitamin D do?
Its established primary function is regulating calcium and phosphate balance and enabling bone mineralization. It increases intestinal calcium absorption; deficiency causes rickets in children and osteomalacia (bone softening) and osteoporosis in adults.
Vitamin D receptors also occur in many tissues, and laboratory research shows effects such as immune regulation, control of cell proliferation and suppression of inflammation. Whether these laboratory effects translate into disease prevention in humans is precisely this article’s subject —and for most diseases the answer has been “no”.
A sentence removed from our old text. The earlier version said vitamin D was “necessary for heart-rate regulation, thyroid function and normal blood clotting”. This statement is unsupported:
- The vitamin needed for clotting is not D but vitamin K —there was most likely confusion here.
- Its effect on heart rhythm is not direct; it is indirect through calcium. Moreover, the relationship is reversed: high calcium resulting from excessive vitamin D causes arrhythmia.
- Its relationship with the thyroid is only observational .
Where do we obtain vitamin D?
An important correction: Our old text said “green leafy vegetables contain small amounts of vitamin D”. This is incorrect. No vegetable, fruit, grain or legume contains vitamin D—the amount is zero. The only meaningful source in the plant kingdom is ultraviolet-exposed mushrooms (the D2 form).
| Source | Vitamin D amount |
|---|---|
| Fish oil (1 tablespoon) | 1.360 IU |
| Trout (85 g) | 645 IU |
| Salmon (85 g) | 570 IU |
| UV-exposed mushrooms (half a cup) | 366 IU |
| Vitamin-D-fortified milk (1 cup) | 120 IU |
| Egg yolk (1 large egg) | 44 IU —a negligible amount |
| Vegetables, fruits, grains | 0 IU |
Türkiye has no mandatory vitamin D fortification of milk, flour or cereal products. This explains why adequate dietary intake is difficult in our country.
Sunshine: are “20-30 minutes daily” sufficient?
This common advice is overly simple and ignores the season. According to a 2024 modeling study for the Mediterranean basin:
| City | Time to produce 1.000 IU (with %25 of body surface exposed) |
|---|---|
| Antalya (37° north) | Fair skin ~4,2 minutes; dark skin ~20,9 minutes |
| Istanbul (41° north) | Fair skin ~5,9 minutes; dark skin ~29,6 minutes |
But the main issue is season, not duration. At Türkiye’s latitudes, UVB radiation enabling synthesis is absent in November, December and Januaryand nearly absent in February and October. Effective synthesis occurs from early March to mid-October, between 10:00-16:00 during the day. Thus, winter sunshine alone is insufficient —however many minutes you stay outside.
Regarding sunscreen: Normal real-world sunscreen use does not appear to cause vitamin D deficiency because people do not apply it as thickly as in laboratory conditions. Therefore “do not use sunscreen for vitamin D” is incorrect and harmful advice —especially on an oncology website. Skin cancer protection takes priority; vitamin D is supplemented if needed.
Regarding sunscreen: Normal real-world sunscreen use does not appear to cause vitamin D deficiency because people do not apply it as thickly as in laboratory conditions. Therefore “do not use sunscreen for vitamin D” is incorrect and harmful advice —especially on an oncology website. Skin cancer protection takes priority; vitamin D is supplemented if needed.
Where did the idea originate?
The vitamin D–cancer hypothesis arose in the 1980s from cancer maps across United States regions: some cancers were more common in less-sunny northern states. This led to the chain “sunshine → vitamin D → protection”.
Hundreds of observational studies then supported the association: higher blood vitamin D was associated particularly with lower colorectal cancer risk. Laboratory research offered mechanisms: slowed cell proliferation, suppressed inflammation and reduced signals mediating cancer spread.
The hypothesis was strong, consistent and mechanistically supported. One thing remained: randomized testing.
What did randomized trials say?
Observational studies say people with higher vitamin D develop less cancer. Randomized trials answer a different, harder question: “Does giving vitamin D reduce cancer?” These are different questions—and their answers differed.
| Trial | Participants and dose | Cancer incidence | Cancer mortality |
|---|---|---|---|
| VITAL NEJM 2019, United States |
25.871 people, daily 2000 IU, 5,3 years | HR 0,96 (%95 CI 0,88-1,06), p=0,47 — no difference | HR 0,83 (0,67-1,02) — not significant |
| D-Health Lancet Diabetes Endocrinol 2022 / Eur J Intern Med 2025, Australia |
21.315 people, monthly 60.000 IU, 5,7 years | HR 1,02 (0,95-1,10) — no difference | HR 1,15 (0,96-1,39) — numerically worse |
| FIND Finland |
2.495 people, 1600 or 3200 IU daily, 5 years | No significant difference between groups | — |
| ViDA New Zealand |
Monthly 100.000 IU | No association with overall cancer risk | HR 0,97 (0,64-1,47) |
| WHI 22-year follow-up, Ann Intern Med 2024 |
36.282 women, 400 IU + 1000 mg calcium | HR 0,97 (0,93-1,01) — no difference | HR 0,93 (0,87-0,99) — slight reduction; however, cardiovascular mortality HR 1,06 (1,01-1,12) increased |
Does vitamin D supplementation change cancer incidence?
Hazard ratio (HR); 1,00 = no difference. The closer a bar is to 1,00, the less effect there is.
VITAL (2000 IU/day)
HR 0,96
D-Health (monthly bolus)
HR 1,02
WHI (400 IU + calcium)
HR 0,97
Combined randomized trials
RR 0,98
In a meta-analysis combining ten randomized trials and 6.547 cancer cases, the result was RR 0,98 (%95 CI 0,93-1,03), p=0,42 —meaning no effect in any subgroup either. For cancer development , this question is now considered settled.
Interesting VITAL details
VITAL’s primary outcome was negative, but secondary and exploratory analyses had notable findings:
- Advanced (metastatic or fatal) cancer: HR 0,83 (0,69-0,99), p=0,04—less advanced cancer occurred with vitamin D.
- Striking difference by body mass index: in normal-weight people (BMI <25), HR 0,62 (0,45-0,86); in overweight people 0,89; in obese people 1,05. The interaction was significant (p=0,03).
- Time-lag analysis: excluding the first 2 years, cancer mortality HR 0,75 (0,59-0,96) became significant.
Why interpret these findings cautiously? All three are secondary or post-hoc analyses. When a primary result is negative, subsequently discovered subgroup differences generate hypotheses rather than establish conclusions. The most likely explanation of the BMI difference is not biological but pharmacokinetic: vitamin D is stored in fat and distributed over a larger volume, so the same dose raises blood levels less in obese people. Lack of effect in obesity may therefore mean inadequate dosing rather than vitamin D not working.
Genetic evidence: Mendelian randomization
This is the most decisive part of the debate and was absent from our old article.
What is Mendelian randomization? Because of inherited gene variants, some people have higher or lower vitamin D throughout life . Since these genes are randomly distributed at birth, these people can be viewed as a randomized trial conducted by nature —free of confounding from lifestyle, diet or disease.
The logic is: If low vitamin D really causes cancer, people genetically predisposed to low levels throughout life should develop cancer more often.
The logic is: If low vitamin D really causes cancer, people genetically predisposed to low levels throughout life should develop cancer more often.
A systematic review of thirty-one Mendelian randomization studies gives a clear conclusion: “Mendelian randomization analyses do not support a causal relationship between 25-hydroxyvitamin D and cancer incidence or mortality.”
| Cancer type | Risk ratio for genetically predicted vitamin D |
|---|---|
| All cancers | 0,98 (0,93-1,04) |
| Colorectal | 0,97 (0,88-1,07) |
| Breast | 1,00 (0,98-1,02) |
| Prostate | 0,99 (0,98-1,01) |
| Lung | 1,00 (0,93-1,03) |
| Pancreatic | No consistent signal |
A UK Biobank analysis of 438.870 people and 46.155 cancers found the same: cancer risk 0,97 (0,91-1,04), cancer mortality 0,97 (0,84-1,11). In the authors’ words, the confidence intervals are “narrow enough to exclude all but very small effect sizes.”
Why did observational studies mislead?
Three mechanisms act together:
| Mechanism | How it works |
|---|---|
| Reverse causation | Disease lowers vitamin D; vitamin D does not cause the disease. 25(OH)D is a “negative acute-phase reactant”: levels of its blood carrier proteins, vitamin-D-binding protein and albumin, fall during inflammation—meaning inflammation lowers measured levels independently of body stores. Low vitamin D found in someone newly diagnosed with cancer may be the disease’s consequence . |
| Being a health marker | People who go outdoors, exercise, eat balanced diets, have normal weight and no chronic disease have higher vitamin D. These people already develop less cancer. Vitamin D is not the cause here but a sign of health. |
| Obesity | Adipose tissue traps and dilutes vitamin D. Obese people have both lower vitamin D and higher cancer risk—but the link is not causal; it reflects a shared third factor . |
The clearest illustration of this confusion: skin cancer. A meta-analysis of thirteen prospective studies found HIGHER melanoma risk in people with higher blood vitamin D (for every 30 nmol/L increase, risk ratio 1,42). For basal cell carcinoma, 1,41; for keratinocyte cancers, 1,30.
Does vitamin D cause skin cancer? No. Because the same analysis found no association with dietary or supplemental vitamin D. The explanation is simple: blood vitamin D also indicates how much sunshine someone receives —and sunshine causes skin cancer.
The same logic works in reverse: High blood vitamin D appears associated with cancer risk because it marks a healthier lifestyle. Observational studies therefore cannot answer the cause-and-effect question.
Does vitamin D cause skin cancer? No. Because the same analysis found no association with dietary or supplemental vitamin D. The explanation is simple: blood vitamin D also indicates how much sunshine someone receives —and sunshine causes skin cancer.
The same logic works in reverse: High blood vitamin D appears associated with cancer risk because it marks a healthier lifestyle. Observational studies therefore cannot answer the cause-and-effect question.
The only remaining signal: cancer mortality
For cancer development , the debate is over. For cancer mortality , however, a weak but persistent signal remains, with an interesting feature: it appears only with daily doses.
Cancer mortality—by dosing schedule
14 randomized trials, 104.727 participants (Kuznia et al., 2023 individual patient data meta-analysis)
Daily dosing (10 studies)
RR 0,88
All studies combined
RR 0,94
Loading (bolus) dosing (4 studies)
RR 1,07
Daily dosing: %12 reduction (RR 0,88; %95 CI 0,78-0,98; p=0,019). Bolus dosing: no effect, even the opposite direction (RR 1,07; 0,91-1,24). Interaction p=0,042. Combining all studies gives a nonsignificant result (RR 0,94; 0,86-1,02).
Similarly, a meta-analysis published in 2019 found for cancer mortality RR 0,87 (0,79-0,96), again only with daily dosing .
How should this signal be read? Three things are simultaneously true:
- The signal may be real and physiologically plausible: monthly megadoses create sharp peaks and deep troughs, while low daily dosing maintains stable levels.
- The signal is fragile: it loses significance when all studies are combined in the individual patient data analysis.
- The signal is contradictory: in D-Health, cancer mortality numerically increased (HR 1,15)—although it also used monthly boluses.
Vitamin D in cancer treatment: what did studies show?
Cancer prevention and treating a cancer patient are separate questions. Randomized studies also address the latter.
| Trial | What was done | Result |
|---|---|---|
| SUNSHINE JAMA 2019 |
139 metastatic colorectal cancer patients: high dose (8000 → 4000 IU) versus standard dose (400 IU), with chemotherapy | Median progression-free survival 13,0 versus 11,0 months; p=0,07 — primary endpoint NOT MET. Response %58 versus %63; median overall survival 24,3 months in both arms. |
| SOLARIS ESMO 2024 |
SUNSHINE’s confirmatory trial: 455 patients, same design | Progression-free survival 11,8 versus 10,3 months, p=0,25; overall survival 25,6 versus 27,0 months, p=0,66. NEGATIVE. Researchers: high-dose vitamin D “cannot be recommended as a treatment.” |
| AMATERASU JAMA 2019 |
417 digestive tract cancer patients: postoperative 2000 IU/day | 5-year relapse-free survival %77 versus %69 — not statistically significant. A signal appeared only in a post-hoc subgroup with intermediate baseline levels. |
| ProsD Br J Cancer 2025 |
123 prostate cancer patients under active surveillance: monthly 50.000 IU, 24 months | For treatment-free time and progression, no difference (p=0,44 and p=0,60) |
Correcting an error in our old text. The earlier version said “SUNSHINE showed improved progression-free survival with high-dose vitamin D”. This is incorrect: the trial missed its primary endpoint (p=0,07), and overall survival did not differ. The reported positive result came from a multivariable-adjusted secondary analysis.
More importantly, the trial designed to test this signal was three times larger : SOLARIS in 2024 produced entirely negative results. This illustrates why phase 2 signals require caution.
More importantly, the trial designed to test this signal was three times larger : SOLARIS in 2024 produced entirely negative results. This illustrates why phase 2 signals require caution.
Vitamin D’s real place in oncology
The summary so far: vitamin D is not a cancer drug. Yet in oncology practice it has a real, important role —absent entirely from our earlier article.
1. Correcting deficiency before bone-protective drugs—the clearest indication.
Denosumab and zoledronic acidare widely used in patients with bone metastases or risk of bone loss. They lower blood calcium, and vitamin D deficiency may cause severe hypocalcemia .
Denosumab and zoledronic acidare widely used in patients with bone metastases or risk of bone loss. They lower blood calcium, and vitamin D deficiency may cause severe hypocalcemia .
- Hypocalcemia in registration trials: denosumab %9,6, zoledronic acid %5. In real-world series, grade 2 or higher hypocalcemia with denosumab %9-22can reach this level.
- Daily supplementation of at least 500 mg calcium and 400 IU vitamin Dreduces hypocalcemia risk with zoledronic acid by %27and with denosumab by %40 .
- Practical rule: The first dose must be preceded by prior correction of vitamin D deficiency and hypocalcemia; check baseline calcium, phosphate and kidney function, then check calcium before every dose.
- Risk is markedly higher with kidney failure.
| Situation | Approach |
|---|---|
| An aromatase inhibitor or androgen-deprivation therapy causing bone loss | Daily 1.200 mg calcium + 800-2.000 IU vitamin D; baseline bone density and fracture risk assessment |
| Aromatase-inhibitor joint pain | Vitamin D does not prevent it. See below. |
| Long-term corticosteroid use | Vitamin D and calcium as part of bone protection |
An instructive example: aromatase-inhibitor joint pain. Many breast cancer patients taking aromatase inhibitors develop joint pain; observational studies reported less pain with vitamin D above 40 ng/mL. It seemed promising.
Randomized testing compared weekly 50.000 IU for 12 weeks followed by daily 2.000 IU with daily 800 IU. Joint pain occurred in %54 versus %57 —no difference. The trial was stopped early for futility. A 2024 review of six studies concluded: three observational studies suggested benefit; all three randomized trials were negative.
This is a miniature model of the entire article: When observational and randomized studies answer the same question differently, the randomized trial is correct.
Randomized testing compared weekly 50.000 IU for 12 weeks followed by daily 2.000 IU with daily 800 IU. Joint pain occurred in %54 versus %57 —no difference. The trial was stopped early for futility. A 2024 review of six studies concluded: three observational studies suggested benefit; all three randomized trials were negative.
This is a miniature model of the entire article: When observational and randomized studies answer the same question differently, the randomized trial is correct.
Immunotherapy—new and exciting, but still a hypothesis. In 2023, two observational studies reported better outcomes among immune-checkpoint-inhibitor patients with normal vitamin D. In an advanced melanoma series of 200 patients, response was %56 versus %36,2, and progression-free survival 11,25 versus 5,75 months . PROVIDENCE found longer overall survival and less thyroid toxicity with vitamin D replacement.
Neither study was randomized , and vitamin D here most likely marks general condition and inflammatory burden —precisely the reverse-causation trap described here. Without randomized confirmation, these findings cannot guide treatment decisions.
Neither study was randomized , and vitamin D here most likely marks general condition and inflammatory burden —precisely the reverse-causation trap described here. Without randomized confirmation, these findings cannot guide treatment decisions.
Guidelines changed: the 2024 turning point
The Endocrine Society’s 2024 guideline reversed a decade of practice. The 2011 guideline encouraged investigating deficiency and used 30 ng/mL as the sufficiency threshold. The 2024 guideline:
- Recommends AGAINST routine 25(OH)D measurement in healthy adults —and this applies to obese and dark-skinned people included all healthy groups.
- Recommends AGAINST routine supplementation in healthy adults aged 19-74 ; reference daily intake (600 IU, above age 70: 800 IU) is sufficient.
- No longer supports the 30 ng/mL threshold: “Clinical trials have not established 25(OH)D levels providing outcome-specific benefits.”
- Low daily dosingrather than intermittent high dosing is preferred.
| Source | Position |
|---|---|
| United States National Academy of Medicine (2011) | Daily requirement 600 IU (above age 70, 800 IU); upper limit 4.000 IU. Sufficiency threshold 20 ng/mL (50 nmol/L); potential side effects above 50 ng/mL |
| United States Preventive Services Task Force | In asymptomatic adults, evidence for vitamin D screening is insufficient; for supplementation to prevent cancer and cardiovascular disease, evidence is also insufficient |
| Endocrine Society (2024) | See the box above |
The situation in Türkiye
| Topic | Information |
|---|---|
| Deficiency prevalence | Among Turkish adults, approximately %60 have 25(OH)D below 20 ng/mL |
| Food fortification | None. There is no mandatory vitamin D addition to milk, flour or grains |
| Support program for pregnant women | Ministry of Health program: 1.200 IU daily (9 drops), from pregnancy week 12 throughout pregnancy and 6 months postpartum as well |
| Restrictions on testing | Ministry of Health regulation dated 27 December 2019: 25(OH)D cannot be ordered in primary care (family medicine). In secondary and tertiary care, only certain specialties may request it: pediatrics, internal medicine and subspecialties, gynecology, physical medicine, orthopedics and neurology. At least 90 days between tests are required. |
| Turkish consensus recommendation (2026) | Deficiency <20 ng/mL, severe deficiency <12 ng/mL, target 20-50 ng/mL. Indication-based testing, not universal screening. Adults 800-2.000 IU/day; above age 75, 2.000 IU/day; pregnancy 2.000-2.500 IU/day; obesity or malabsorption 3.000-6.000 IU/day, individually tailored. After initiation, 8-12 weeks later recheck. |
Türkiye’s particular situation: High deficiency reflects the combined effects of northern latitude, absent winter UVB, no food fortification and covering clothing. This does not justify giving everyone vitamin D; it does show that deficiency is genuinely common here and should be investigated when clinically indicated . Testing restrictions reflect an attempt to maintain this balance.
Can too much cause harm? Yes
| Study | Finding |
|---|---|
| Burt et al., JAMA 2019 300 people, 3 years |
Daily 400 / 4.000 / 10.000 IU were compared. Forearm bone density showed dose-dependent DECREASES: %-1,4 / %-2,6 / %-3,6. No gain in bone strength. Increased urinary calcium: %17 / %22 / %31. |
| Sanders et al., JAMA 2010 | In women older than 70, a single annual dose of 500.000 IU: falls and fractures increased; excess events clustered in the first 3 months after dosing |
| WHI, 22-year follow-up | Among calcium + vitamin D recipients, cardiovascular mortality HR 1,06 (1,01-1,12); increased urinary stones |
Vitamin D toxicityoccurs when blood levels rise above 150 ng/mL (375 nmol/L) and is almost always caused by supplements —never sunshine, because skin automatically limits production. High blood calcium causes nausea, vomiting, weakness and altered consciousness; severe cases involve kidney failure, tissue calcification and arrhythmias.
The daily upper limit is 4.000 IU and should not be exceeded except for physician-supervised treatment of documented deficiency. As Burt showed, “more is better” is incorrect —high doses reduced rather than increased bone density.
The daily upper limit is 4.000 IU and should not be exceeded except for physician-supervised treatment of documented deficiency. As Burt showed, “more is better” is incorrect —high doses reduced rather than increased bone density.
Does vitamin D increase cancer risk? Some observational studies suggested that very high blood levels may increase pancreatic and prostate cancer risk. These findings, however, have not been confirmed and randomized trials, VITAL and D-Health, showed no such excess. Our old text stated this too definitively; we have softened it. The only exception is skin cancer , where the responsible factor is not vitamin D but what produces it: sunshine.
What should I do?
- Do not take vitamin D to prevent cancer. It has not shown effectiveness for this purpose, and current evidence has settled the question.
- Healthy people do not need routine measurement. Guidelines do not recommend it.
- Measure when clinically indicated: Bone pain and muscle weakness, malabsorption (celiac disease, Crohn’s, bariatric surgery), chronic kidney disease, prolonged cortisone or antiepileptic use, unexplained low calcium or high parathyroid hormone, and before starting bone-protective medicine.
- If deficiency is found, prefer low daily dosing —avoid monthly or annual megadoses.
- Typical adult dose 800-2.000 IU/day; upper limit 4.000 IU/day. Obesity or malabsorption may require higher doses, but that is a physician’s decision.
- If you have cancer and will start denosumab or zoledronic acid, vitamin D deficiency should be corrected before the first dose. This is this article’s clearest and most important point.
- Do not abandon sun protection. Stopping sunscreen for vitamin D increases skin cancer risk and loses more than it gains.
- In the diet, oily fish (2 portions weekly) is the most practical natural source.
Frequently asked questions
- Does vitamin D deficiency cause cancer?
- According to current evidence, no. Large randomized trials and genetic Mendelian randomization studies show no causal relationship. Low vitamin D frequently found in cancer patients most likely is the consequenceof disease and associated conditions, not the cause.
- Does supplementation prevent cancer?
- No. VITAL (HR 0,96), D-Health (HR 1,02), FIND, ViDA, WHI and their combined analysis (RR 0,98) consistently showed no effect.
- Why do so many studies report an association?
- Because association (correlation) and causation are different. People with higher vitamin D go outdoors, exercise, have normal weight and no chronic disease; they already develop less cancer. Disease and inflammation also lower measured vitamin D.
- I have cancer; should I take vitamin D?
- To treat or slow cancer, no —randomized studies including SOLARIS do not support this. But yes for bone health: particularly with denosumab, zoledronic acid, aromatase inhibitors or androgen deprivation, vitamin D and calcium are necessary supportive treatment.
- What should my blood vitamin D be?
- Current guidelines avoid defining an ideal level. For bone health, 20 ng/mL (50 nmol/L) or above is sufficient for almost everyone; Türkiye’s 2026 consensus sets a target of 20-50 ng/mL . Higher is not better.
- Is a single monthly dose not more practical?
- Practical, but not preferred. Guidelines recommend low daily doses. The weak cancer-mortality benefit signal occurred only with daily, not monthly doses. Annual megadoses make falls and fractures more frequent as demonstrated in research.
- Can winter sunshine provide vitamin D?
- At Türkiye’s latitude, not in November, December and January —insufficient UVB reaches the ground. February and October are limited too. Effective production occurs from early March to mid-October, between 10:00-16:00.
- Does sunscreen lower my vitamin D?
- Not meaningfully in real life, because most people apply it less thickly than under laboratory conditions. Skin cancer protection is the priority; supplementation when needed is much safer than unprotected sunbathing.
- Are mushrooms a source?
- Yes, but only those exposed to ultraviolet light . They are the only meaningful plant-kingdom source and contain D2. Ordinary vegetables contain no vitamin D.
Glossary
- 25(OH)D
- 25-hydroxyvitamin D. The blood measurement indicating vitamin D status.
- IU
- International unit. 40 IU = 1 microgram of vitamin D.
- Randomized controlled trial
- A study randomly assigning participants to groups. The only design capable of answering cause-and-effect questions.
- Observational study
- Follow-up without intervention. Shows association, not cause.
- Mendelian randomization
- A method testing causation using inherited genetic differences.
- Reverse causation
- Mistaking an effect for a cause; for example, disease lowers vitamin D, but low vitamin D is thought to cause disease.
- Confounder
- A third factor affecting both variables and creating a false association.
- HR / RR
- Risk ratio. 1,00 means no difference; if the confidence interval includes 1, the result is nonsignificant.
- Bolus dose
- A single large dose given monthly or annually.
- Hypocalcemia
- Low blood calcium. An important side effect of bone-protective medicines.
DROZDOGAN Academy commentary
The vitamin D–cancer story is among medicine’s most instructive examples of hoped-for but unconfirmed benefit. Our assessment follows.
⚡ Why does this matter?
Because the issue is not a vitamin but how to read evidence. The hypothesis seemed flawless: geographical observations, hundreds of observational studies, laboratory mechanisms, low cost and presumed safety. Yet randomized testing overturned it. The lesson extends beyond vitamin D: a strong hypothesis is not strong evidence. All future oncology supplement claims should be viewed through this lens.✅ What we can be sure about today
First, the question really has been answered. This cannot be said in most nutrition debates. VITAL’s 25.871 participants, D-Health’s 21.315, WHI’s 36.282 and their pooled analysis (RR 0,98) point the same way. Moreover, another method— Mendelian randomization —independently confirms it. Two distinct methods reaching the same conclusion represent among the strongest achievable evidence.Second, we can now measure how powerfully reverse causation misleads. The skin cancer example is elegant evidence: with high blood vitamin D, melanoma occurs more often , but supplement users show no association. We are measuring not vitamin D’s effect but sun-exposure habits. The same mechanism, reversed, produced the prevention claim.
Third, guidelines acted boldly. The Endocrine Society’s abandonment in 2024 of its 2011 threshold and advice not to test healthy adults is an uncommon medical reversal deserving recognition.
⚠️ Questions remain
Cancer mortality is not fully resolved. A %12 reduction signal with daily dosing appears in two meta-analyses and is physiologically plausible. However, it loses significance when all studies are pooled in the individual patient data analysis, points the opposite way in D-Health, and these analyses were not prespecified. Calling it proven is wrong; declaring it nonexistent is premature.VITAL’s BMI finding is interesting but uninterpreted. The %38 reduction in advanced cancer risk in normal-weight people (HR 0,62) may be real, but the most likely explanation is not biology but inadequate dosing: the same dose raises blood levels less in obese people. This raises the question of higher doses in obesity, but a trial testing this does not exist.
And a warning: “Vitamin D does not cause cancer” does notmean “vitamin D is unimportant”. Approximately %60 of Turkish adults have deficiency, there is no fortification and winter sunshine is insufficient. This is a real bone-health problem —just not a cancer issue.
🩺 Our practical position
1. We do not recommend vitamin D for cancer prevention. This stance arises not from absence of evidence but from evidence being available —the question was asked and answered.2. For cancer patients, vitamin D is supportive treatment, not cancer treatment. Explain this clearly; otherwise patients may expect it to replace actual treatment.
3. The clearest point: Assess vitamin D before the first dose in every patient starting denosumab or zoledronic acid. This is necessary, not controversial, and neglect can cause severe hypocalcemia. It is this article’s only mandatory-action item.
4. Testing requires a reason. Türkiye’s testing restriction may frustrate, but its logic is correct: measuring 25(OH)D in a healthy person usually only creates unnecessary supplementation and anxiety.
5. Daily dosing is preferable to monthly dosing. Monthly megadose ampoules are common in Türkiye and seem practical, but guidelines prefer low daily dosing, while annual megadoses have shown harm.
6. Do not stop sunscreen. As an oncology website, we must say clearly: unprotected sunbathing for vitamin D is a trade-off losing more than it gains.
❓ Open questions
Is the daily-dose cancer-mortality reduction real—will a prespecified trial designed to test it be conducted? Would outcomes change in obese people with weight-based dosing ? Would genuinely deficient people benefit differently, given that most VITAL participants were not deficient? This frequent criticism remains unanswered. Will the observational immunotherapy association survive randomized testing?Our brief judgment: Vitamin D is necessary for bone, not a cancer medicine. Correct deficiency; without it, do not pursue supplementation; never take megadoses. Remember the main lesson: a low blood level does not mean that giving the substance will help. In oncology, this applies far more broadly than vitamin D.
Transparency note. (1) VITAL’s total cancer incidence subgroup analysis by BMI had an exact risk ratio and confidence interval that could not be verified from the primary source; only direction and approximate size were given. (2) Extended VITAL follow-up published during 2022-2026 could not be found; this does not mean no such publication exists. (3) AMATERASU and FIND exact risk ratios could not be verified from primary sources. (4) Sanders 2010 exact fall and fracture rates, and WHIcolorectal cancer and kidney-stone risk ratios, were not given numerically because they could not be verified. (5) Pancreatic and prostate cancer claims of increased risk had effect sizes unverifiable from primary sources; no numbers were given and the claims were softened. (6) ESMO Bone Health guideline calcium and vitamin D doses were unavailable from the full text, so another guideline’s doses were used. (7) The infant vitamin D support program’s current dose and scope could not be verified on Ministry of Health pages; the pregnancy program was verified. (8) For 25(OH)D testing, SGK reimbursement conditions could not be verified; the stated restriction comes from the 2019 Ministry regulation and may have changed. (9) Vitamin D deficiency prevalence in cancer patients was not quantified because no reliable pooled data were found.
This article is for information and does not replace individual medical advice. Your physician should decide testing and supplementation after assessing personal risks and medicines. Tell your oncology team about all supplements during treatment.
References
- Manson JE, et al. Vitamin D supplements and prevention of cancer and cardiovascular disease (VITAL). N Engl J Med 2019;380:33-44.
- Chandler PD, Manson JE, et al. Effect of vitamin D3 supplements on development of advanced cancer: a secondary analysis of the VITAL randomized clinical trial. JAMA Netw Open 2020;3(11):e2025850.
- Neale RE, et al. The D-Health Trial: a randomised controlled trial of the effect of vitamin D on mortality. Lancet Diabetes Endocrinol 2022;10:120-8; cancer incidence results Eur J Intern Med 2025.
- Keum N, et al. Vitamin D supplementation and total cancer incidence and mortality: a meta-analysis of randomized controlled trials. Ann Oncol 2019.
- Kuznia S, et al. Efficacy of vitamin D3 supplementation on cancer mortality: systematic review and individual patient data meta-analysis of randomised controlled trials. Ageing Res Rev 2023.
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3. Wactawski-Wende J. et al. Calcium plus vitamin D supplementation and the risk of colorectal cancer. N Engl J Med 2006.
4. Parfitt AM. Osteomalacia and related disorders. In: Avioli LV, Krane SM, eds. Metabolic bone disease and clinically related disorders. 2nd ed. Philadelphia: WB Saunders, 1990.
5. Freedman DM et al. Prospective study of serum vitamin D and cancer mortality in the United States. J Natl Cancer Inst 2007.
6. Jenab M, et al. Association between pre-diagnostic circulating vitamin D concentration and risk of colorectal cancer in European populations: a nested case-control study. BMJ 2010.
7. D. A. Grotsky et al. BRCA1 loss activates cathepsin L-mediated degradation of 53BP1 in breast cancer cells. The Journal of Cell Biology, 2013.
8. Kathy J. Helzlsouer for the VDPP Steering Committee. Overview of the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers. Am J Epidemiol 2010.
9. Sperati F. et al. Vitamin D supplementation and breast cancer prevention: a systematic review and meta-analysis of randomized clinical trials. PLoS One. 2013.
10. U.S. National İnstitutes of Health Office of Dietary Supplements,Vitamin D
11. Robert Scragg, Kay-Tee Khaw, Les Toop ve ark.
Monthly High-Dose Vitamin D Supplementation and Cancer Risk A Post Hoc Analysis of the Vitamin D Assessment Randomized Clinical Trial.
JAMA Oncol, July 2018.
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