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Vitamin D Fixes a Deficiency. It Was Never Going to Fix Everything.

The nutrient your skin makes from sunlight, the vitamin that helps decide where calcium ends up, and why the capsule on the shelf holds six times what the label reference says.

18 minutesPublished October 25, 20260 likes0 comments

What you'll learn

  • Why vitamin D is an unusual vitamin, and why that one fact explains most of the confusion
  • What vitamin K actually does, and why the K in a salad is not the K in the capsule
  • Why bottles say 5,000 IU when the label reference says 800, and where that number came from
  • What happened when someone randomized people to 400, 4,000 and 10,000 IU for three years
  • Why vitamin D is one of the twelve nutrients our own tracker counts, and why your number there will probably look low

How SmartBar applies the deficiency framework

SmartBar assesses products using three things we can verify: ingredient composition, level of processing, and nutritional data. We use two organizing terms throughout our education. Deficiency means something the body needs and isn't getting. Toxicity means a burden the body must process and clear, not a poison.

Vitamin D sits across both, which is what makes it worth its own page. Severe deficiency causes a well-established disease that correction prevents and treats, while adding extra on top of adequacy, in largely replete populations, has repeatedly failed to deliver the broad chronic-disease benefits once predicted for it. Both halves are true, and most writing on this subject gives you only one.

Start here, before any of the science

Two plain facts make everything below easier to follow.

Vitamin D is an unusual vitamin. Most vitamins are things the body cannot make and has to get from food. Humans manufacture vitamin D3 in skin when enough ultraviolet B light reaches it. Chemically it is a secosteroid, and its active form, calcitriol, behaves as a hormone. Researchers sometimes call the name a historical misnomer for exactly that reason, though the terminology is genuinely debated and some argue the original classification was right. Either way, the practical consequence is the same: food was never the main delivery route, which is why so few foods contain much of it.

Vitamin K is not one thing. It is a family. The K in leafy greens is phylloquinone, written K1. The K in a capsule marked K2 is a menaquinone, and that is not one substance either: MK-4 comes mainly from animal tissue, MK-7 from bacterial fermentation. They differ in origin, in how long they persist in blood, and in what has been tested. When someone says "vitamin K," ask which one. The answer usually decides whether the claim attached to it survives.

What each one does when you have enough

Vitamin D is a major regulator of intestinal calcium absorption and of calcium homeostasis. Calcium in food does not simply cross the gut wall. Vitamin D governs how much is absorbed and helps hold blood calcium in the narrow range the body insists on. When vitamin D is low, absorption falls and the body compensates by drawing calcium from the skeleton, because blood chemistry wins that argument every time.

Vitamin K activates proteins involved in bone mineralisation and in the inhibition of soft-tissue calcification. It works as a cofactor: certain proteins are built inactive and require vitamin K to be switched on. Osteocalcin is involved in binding mineral into bone. Matrix Gla protein inhibits calcification in soft tissue and circulates in an inactive form when vitamin K is insufficient.

That is biologically important. It is not the same as proving that taking vitamin D without K2 sends calcium into your arteries. Vascular calcification is driven by kidney function, phosphate handling, inflammation and cell differentiation as well, and vitamin K is a cofactor in that system rather than a traffic controller directing calcium to one destination or another.

What too little looks like

Severe vitamin D deficiency is not subtle. In children it can produce rickets, where growing bone fails to mineralise and deforms under load. In adults the equivalent is osteomalacia, soft and painful bone. These are why the nutrient was discovered and why fortification exists, correcting them works, and this is the strongest evidence in the field. Milder low vitamin D may produce no distinctive symptoms at all, which is one reason online symptom lists are a poor way to work out whether you have it.

There is a second, subtler problem with the word. "Deficiency" gets used for three different things: a disease state, a laboratory cutoff, and eligibility for a supplement. The 2011 Institute of Medicine framework associated a blood level of 20 ng/mL with meeting the needs of nearly all healthy people.[1] The 2024 Endocrine Society guideline moved away from universal thresholds entirely, concluding that no clear evidence defines an optimal level for disease prevention.[2] Keep those apart as you read, because most of the disagreement in this field is about which one is meant.

For vitamin K, outright deficiency is rare in people who eat normally. K1 is abundant in green vegetables and the body recycles vitamin K efficiently. The live research question is a partial one: whether some people carry more inactive matrix Gla protein than is ideal, and whether that matters clinically.

Why they are almost always sold together

The pairing story is elegant. D increases calcium absorption, K activates the protein that inhibits calcification, so taking D alone supposedly floods your blood with calcium that nothing is directing, and without K2 it lands in your arteries. It is coherent, it is the most confidently repeated claim in the subject, and the trial evidence for the conclusion is far thinner than the confidence suggests. The rest of this page checks it against what has been measured.

Why vitamin D is in our tracker, and why your number may look low

SmartBar's Track feature counts twelve micronutrients from the whole foods you log. Vitamin D is one of them, measured against the FDA Daily Value of 20 mcg, which is 800 IU.

Why the Daily Value and not the RDA. The RDA is 600 IU a day for ages one to seventy and 800 for seventy-one and over, an intake estimated to meet the needs of at least 97.5% of the population.[1] The Daily Value is a single label reference set at 20 mcg for everyone four and older, so one number serves every reader of a package.[3] SmartBar reads nutrition off Nutrition Facts panels, which express everything as a percentage of the Daily Value, so using the RDA would have the app and the package quoting different yardsticks at you.

Now the honest part. Vitamin D is close to the worst possible nutrient for a food-only tracker. Few foods naturally contain it. Fatty fish flesh and fish liver oils are among the best sources; beef liver, egg yolks and cheese carry small amounts; mushrooms provide variable vitamin D2, and some are treated with ultraviolet light to raise it.[4] Everything else is fortified or contributes almost nothing. Meanwhile a substantial part of most people's supply is skin synthesis, which Track cannot see, because Track counts food.

So the vitamin D line in Track will read low for many people whose actual status is fine. That is a limit of the measurement, not a statement about your body. We would rather show the gap and explain it than quietly lower the target.

The number on the bottle, and the number on the label

Here is the question that follows immediately, and it deserves a straight answer. If the Daily Value is 800 IU, why does almost every supplement on the shelf contain 2,000, 5,000 or 10,000, and why do so many people online recommend exactly that?

Because different kinds of number get treated as one. A dietary reference like the RDA describes the usual intake needed by healthy people, while the Daily Value is a standardised label reference. A repletion dose is what a clinician prescribes, at higher strength and for a defined purpose, to correct a documented deficiency. A maintenance dose is what continues after that, or what someone takes indefinitely on their own. The 50,000 IU figure circulating online is a repletion dose, lifted out of a supervised eight-week protocol and worn as a lifestyle.

And because a major professional body said so, in print. The 2011 Endocrine Society guideline stated that reaching a blood level above 30 ng/mL may require at least 1,500 to 2,000 IU a day, set treatment for deficient adults at 50,000 IU weekly for eight weeks or 6,000 IU daily, suggested an upper limit of 10,000 IU a day when correcting deficiency against the Institute of Medicine's 4,000, and stated that there is no evidence of a downside to increasing vitamin D intake except in granuloma-forming disorders and lymphoma.[5] That last sentence is the licence the whole market was built on.

Notice what the disagreement was actually about. Not biology. A threshold. If a population threshold is set at 20 ng/mL, substantially fewer people are classified as needing additional intake than if it is set at 30, and that choice drove much of the difference between the Institute of Medicine and the 2011 Endocrine Society positions. In 2024 the same Endocrine Society changed direction substantially, suggesting against routine testing, against supplementation above the dietary reference intake in healthy adults under 75, and concluding that it could not determine a target blood level for disease prevention.[2] Over roughly the same period, use of supplements providing 1,000 IU a day or more rose from 0.3% to 18.2% of US adults.[2]

Then somebody tested those doses. A three-year double-blind trial randomized 311 healthy adults aged 55 to 70, without osteoporosis, to 400, 4,000 or 10,000 IU of vitamin D3 daily and measured bone directly with high-resolution peripheral CT. Compared with 400 IU, three years at 4,000 or 10,000 produced statistically significantly lower radial bone mineral density, and tibial density was lower at 10,000. Hypercalciuria occurred in 17%, 22% and 33% of the three groups with a significant dose-response, and hypercalcemia followed the same pattern, all mild and resolving on retesting.[6]

That is not a scare. It is a randomized trial at exactly the doses being sold, running the length of time people actually take them, and an outcome central to vitamin D's established skeletal role moved the wrong way. Estimated bone strength did not differ between the groups, so this is a bone density finding rather than a fracture one, and it is worth stating at that size.[6]

The other way to overshoot is infrequency rather than strength. A trial randomized 2,256 community-dwelling women aged 70 and over, at high risk of fracture, to a single annual 500,000 IU dose or placebo. Falls rose, incidence rate ratio 1.15, and fractures rose, 1.26, with the excess in falls concentrated in the three months after each dose.[23]

And the part that is true in the other direction, because leaving it out would be the same failure. Higher intakes may genuinely be warranted in specific clinical situations, including documented deficiency, malabsorption and medications that alter vitamin D metabolism. That same 2011 guideline also set higher treatment and maintenance doses for people with obesity.[5] Those are clinical contexts, not default doses anyone should adopt from a video.

What happened when the big trials tested it

VITAL randomized 25,871 US adults, men 50 and over and women 55 and over, including 5,106 African American participants, to 2,000 IU of vitamin D3 daily or placebo, with invasive cancer and major cardiovascular events as the two primary endpoints. Supplementation lowered the incidence of neither.[7]

D-Health randomized 21,315 Australians aged 60 and over to 60,000 IU monthly or placebo for five years, with all-cause mortality as the primary endpoint. It did not reduce it.[8]

Two trials, roughly 47,000 people, five years each, and the headline outcomes did not move.

Why a null trial is not the same as a useless nutrient

A supplementation trial can only test whether adding more helps the people enrolled. A trial recruiting from a largely sufficient population is asking whether excess does anything, which is a different question from whether the nutrient matters. The design that finds no benefit from extra water in well-hydrated people tells you nothing about dehydration.

That framing is not a rescue invented after the results arrived. It was there when the reference intakes were set. The 2011 committee based the requirement on skeletal health alone, finding the evidence for cancer, cardiovascular disease, diabetes and autoimmune outcomes inconsistent, inconclusive as to causality and insufficient to set an intake from. The same report concluded that inadequacy in North America had been overestimated, that higher blood levels were not consistently associated with greater benefit, and that some outcomes showed elevated risk at both low and high levels.[1]

So the defensible position is narrower than either camp wants. Correcting a genuine shortfall does something real. Adding more once you have enough has not delivered what was predicted, across two very large trials and a professional guideline that examined them.

D2, D3, and what a label does not tell you

D2 and D3 are not identical. A meta-analysis of direct comparisons found D3 raised blood 25(OH)D more than D2 overall, although the advantage appeared with bolus dosing and not with daily dosing, and with substantial variation between studies.[9] Mushrooms provide D2, while most supplement marketing centres on D3, so "vitamin D" on a label can describe compounds that behave somewhat differently.

The softgel, the drop of oil, and a claim that is half right

Both nutrients are fat-soluble, which has become a marketing lever. The reasoning offered is that because vitamin D needs fat, a softgel suspending it in coconut or sunflower oil must be absorbed better than a dry tablet.

The mechanism is real, and less absolute than usually stated. Vitamin D3 in the gut is emulsified by bile salts and carried in micelles alongside dietary fat, and it is better absorbed with a fat-containing meal. But a systematic review of 46 studies found absorption also occurs without fat or an oily vehicle, and that the process is not exclusively passive diffusion: it appears to involve membrane carriers, particularly cholesterol transporters.[31]

The evidence underneath the claim is thin and inconsistent. A systematic review favoured oil vehicles but included only three oil studies, against two powder and one ethanol, and its authors called for further work.[10] Later trials found inconsistent effects of meal fat on short-term absorption, in one case favouring the low-fat meal, while longer-term 25(OH)D responses were unchanged; an oil-solubilised dose likewise produced no significant difference taken fasting or with a high-fat meal.[11][12][13]

Absorption is a step, not an outcome, and even the step is unsettled.

K2 on its own terms

Before this section goes further: vitamin K interacts with vitamin K antagonist anticoagulants, warfarin among them. If you take one of these medicines, changes to vitamin K intake are a conversation with your prescriber or pharmacist, not something to act on from a website. Nothing on this page is a reason to start, stop or change any medication.

There is no established daily requirement specifically for K2 or MK-7. Dietary reference values are set for vitamin K as a category, and the FDA Daily Value of 120 mcg is a single figure for vitamin K, not for a particular menaquinone.[3] A supplement label can print a dose. That is not the same as a demonstrated human requirement, and the difference matters when a product is sold on the premise that you have a K2 gap to fill.

The hypothesis was tested properly. The largest relevant trial randomized 365 Danish men aged 65 to 74 with an aortic valve calcification score of at least 300 arbitrary units to 720 µg of MK-7 plus 25 µg of vitamin D daily, or placebo, for 24 months. The primary analysis did not establish a significant reduction in progression.[14] A prespecified secondary analysis of coronary calcification in 304 participants without ischaemic heart disease found a numerically smaller increase with supplementation, but the between-group difference was not statistically significant.[15]

One trial makes the sharpest point in this article. In patients with type 2 diabetes and cardiovascular disease, six months of vitamin K2 reduced circulating inactive matrix Gla protein but did not affect arterial calcification on imaging.[16] The biomarker moved exactly as the mechanism predicts. The imaging outcome did not follow. That gap, between a biomarker moving and a disease process changing, is the single most important thing to understand here.

The pooled picture is genuinely mixed, and mixed within one review. A 2023 meta-analysis of 14 randomized trials found, from the four that could be combined on coronary artery calcification, a small but statistically significant slowing of progression, alongside a clear reduction in inactive matrix Gla protein. The same review records that eight other trials measuring major arterial or valve calcification reported no appreciable benefit, its authors describe vitamin K's role as remaining controversial, and they conclude that more rigorously designed trials are needed.[17] A separate review restricted to chronic kidney disease found no significant change in radiological calcification scores at all.[18]

That is not "K2 does nothing." It is also nowhere near "vitamin D requires K2 or calcium goes into your arteries."

Where the signal is better is bone. A three-year trial in 244 healthy postmenopausal women given 180 µg of MK-7 daily found slowed bone loss at some skeletal sites.[19] A real finding, in a specific population, at a specific dose, on a bone endpoint. It does not establish that vitamin D supplementation requires K2, which is the claim it is most often used to support.

And magnesium?

The next version of the stack adds magnesium, because the enzymes that make and break down vitamin D depend on it. That biology is real. A randomized trial of 180 adults aged 40 to 85, with magnesium doses personalised to each person's dietary intake, found that supplementation raised 25(OH)D3 when starting levels were below roughly 30 ng/mL and lowered it when starting levels were between about 30 and 50.[20] Not an amplifier, then, but something that moves in different directions depending on where you begin, measured on vitamin D metabolism rather than on any health outcome, in participants with a history of colorectal polyps.

Another real mechanism, converted into a universal purchasing rule well before the outcome evidence exists. That is the pattern this whole page is about.

The pairing, and who is selling the certainty

The mechanism is real, the inference from it is intuitive, the trials built to test the inference produced a split and largely unconvincing result, and the confident version, that vitamin D without K2 sends calcium into your arteries, is an inference presented as a finding.

Notice who benefits from the confident version. It sells a second bottle to everyone already buying the first, a combination product at a premium over two separates, and a blood test to establish your need, in a field where the current guideline says no target level has been established.[2] We sell no supplements, score none, and have no position to protect. We are telling you what has been measured, including the parts that did not work.

Where food actually sits

For vitamin K the split follows the family. K1 is the green vegetable form, K2 other than MK-4 is bacterially made and appears in fermented foods, and MK-4 comes from animal tissue conversion, mainly in meat, liver and egg yolk.[21]

Treat published food K2 numbers with caution. Measured properly, content varies enormously: across eight cheeses, vitamin K ranged from under 0.5 to 32 µg per 100 g and the fraction available for absorption from 6.4% to 80%, and longer ripening did not reliably raise it.[22] Most confident figures online originate with companies selling K2.

Key takeaways

  • Vitamin D behaves like a hormone your skin makes, not a nutrient you eat. Food captures only part of the supply: where UVB conditions permit, skin synthesis contributes substantially, and fortified foods or supplements dominate for other people and seasons.
  • Correcting severe deficiency is powerful. Adding more on top of adequacy has not delivered the broad chronic-disease benefits once predicted for it. Two trials totalling roughly 47,000 people found no effect on cancer, cardiovascular events or mortality.
  • Very large intermittent doses are not automatically better. One annual 500,000 IU regimen increased falls and fractures in older women, and current guidance favours daily lower doses over intermittent high ones in adults over 50 when supplementation is indicated.
  • Much of the gap between 800 IU and the bottle came from a threshold dispute, not from new evidence that everyone biologically needs several times more. Three years at 4,000 or 10,000 IU produced lower bone density than 400, and the professional body that set the higher threshold now says it cannot identify a target blood level for disease prevention and suggests against routine testing.
  • The D-plus-K2 mechanism is real and the outcome evidence is not settled. K2 has been shown to move the matrix Gla protein biomarker without changing arterial calcification on imaging, which is the whole lesson in one result.

How to think about this in thirty seconds

  1. Ask whether the claim is about correcting a shortfall or adding more on top of enough. Almost every disagreement here collapses into that distinction.
  2. Ask which number is being quoted: a population dietary reference, a time-limited repletion dose, or an indefinite maintenance dose.
  3. Ask which vitamin K is meant. K1, MK-4 and MK-7 are not interchangeable, and neither is the evidence for them.
  4. Treat a mechanism as a reason to run a trial, not as the result of one.
  5. Remember that absorption is a step, not an outcome, and ask who benefits if you believe the confident version.

What SmartBar does with this

SmartBar carries no dietary supplements. They are not scored, not in the product database, not in the Whole Foods Library, and cannot be logged in Track. A Supplement Facts panel is a reason a submission gets rejected. We have nothing to sell you at the end of this page, which is the only reason a page like this can be written honestly.

What we do carry is whole food, and vitamin D is one of the twelve micronutrients Track counts against the FDA Daily Value of 20 mcg. We have said plainly why that number will often read low and what it does not mean, and we would rather state the size of that relationship accurately than inflate it.

The framework holds here unusually cleanly. Vitamin D is a genuine deficiency story, with a real disease at the bottom of it and a real correction. It is also the clearest case in nutrition of what happens when a deficiency story is stretched into a treatment story: the trials get run, the outcomes do not follow, and the marketing continues regardless.

This article is educational and is not medical advice. Nothing here is a reason to start, stop or change any medication, including prescription vitamin D. If you take a vitamin K antagonist anticoagulant such as warfarin, changes to vitamin K intake belong in a conversation with your prescriber or pharmacist. Vitamin D status is genuinely individual: kidney or liver disease, conditions affecting fat absorption, granulomatous disease, pregnancy, older age, medications and limited sun exposure all change the picture, and those belong with a qualified clinician who knows your history rather than with anything you read online, including here.

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References

  1. Institute of Medicine (2011). Dietary Reference Intakes for Calcium and Vitamin D. Washington, DC: The National Academies Press. DOI: 10.17226/13050. Free full text: NCBI Bookshelf NBK56050. See also Ross, A.C., Manson, J.E., Abrams, S.A., et al. (2011), Journal of Clinical Endocrinology & Metabolism 96(1):53–58. (EAR 400 IU/day above age 1; RDA 600 IU/day ages 1–70 and 800 IU/day 71 and over, covering at least 97.5% of the population and corresponding to serum 25(OH)D of at least 20 ng/mL. Requirements set on skeletal health alone; evidence for cancer, cardiovascular disease, diabetes and autoimmune outcomes judged inconsistent, inconclusive as to causality and insufficient. Prevalence of inadequacy in North America judged overestimated; higher serum levels not consistently associated with greater benefit; U-shaped risk for some outcomes. Tolerable Upper Intake Level 4,000 IU/day.)

  2. Demay, M.B., Pittas, A.G., Bikle, D.D., et al. (2024). "Vitamin D for the Prevention of Disease: An Endocrine Society Clinical Practice Guideline." Journal of Clinical Endocrinology & Metabolism. DOI: 10.1210/clinem/dgae290. PMID: 38828931. (Suggests against routine 25(OH)D testing absent established indications, including in obesity, dark complexion and pregnancy; against empiric supplementation above the DRI in healthy adults under 75; for empiric supplementation in ages 1–18, adults over 75, pregnancy and high-risk prediabetes; and daily lower-dose rather than intermittent high-dose administration for people over 50 with an indication. The panel could not determine blood-level thresholds for adequacy or disease prevention and found no clear evidence defining an optimal target. Records that use of supplements providing ≥1,000 IU/day rose from 0.3% to 18.2% between NHANES 1999–2000 and 2013–2014. Replaces the Society's 2011 guideline; explicitly does not replace the IOM DRIs.)

  3. U.S. Food and Drug Administration, "Daily Value and Percent Daily Value on the Nutrition and Supplement Facts Labels," Reference Guide: Daily Values for Nutrients. https://www.fda.gov/media/135301/download (Vitamin D 20 mcg; vitamin K 120 mcg. The Daily Value is a single population-wide label reference set at the highest life-stage requirement, not a personalised requirement, which is why it exceeds the adult RDA. The vitamin K value is for vitamin K as a category; no separate reference value exists for MK-7 or for menaquinones generally.)

  4. National Institutes of Health, Office of Dietary Supplements, "Vitamin D — Health Professional Fact Sheet." https://ods.od.nih.gov/factsheets/VitaminD-HealthProfessional/ (Few foods naturally contain vitamin D; fatty fish flesh and fish liver oils among the best sources; beef liver, egg yolks and cheese contain small amounts, primarily D3 and its metabolite 25(OH)D3; mushrooms provide variable D2, some UV-treated to raise it.)

  5. Holick, M.F., Binkley, N.C., Bischoff-Ferrari, H.A., Gordon, C.M., Hanley, D.A., Heaney, R.P., Murad, M.H., Weaver, C.M. (2011). "Evaluation, Treatment, and Prevention of Vitamin D Deficiency: an Endocrine Society Clinical Practice Guideline." Journal of Clinical Endocrinology & Metabolism 96(7):1911–1930. (Suggests ≥1,500–2,000 IU/day may be needed to hold 25(OH)D above 30 ng/mL; treatment of deficient adults at 50,000 IU weekly for 8 weeks or 6,000 IU daily then maintenance; upper limit of 10,000 IU/day suggested when correcting deficiency, against the IOM's 4,000; 2–3 times the age-group requirement for obese patients and those on anticonvulsants, glucocorticoids, antifungals and AIDS medications; and states there is no evidence of a downside to increasing intake except in chronic granuloma-forming disorders and lymphoma. Maintenance after repletion was set at 1,500–2,000 IU/day, and at 3,000–6,000 IU/day for patients with obesity, malabsorption syndromes or medications affecting vitamin D metabolism, circumstances that can be chronic. Cited as the historical origin of current high-dose practice. The Society's 2024 prevention guideline takes a substantially different approach to routine testing, supplementation above the DRI and universal target thresholds in generally healthy populations.[2])

  6. Burt, L.A., Billington, E.O., Rose, M.S., Raymond, D.A., Hanley, D.A., Boyd, S.K. (2019). "Effect of High-Dose Vitamin D Supplementation on Volumetric Bone Density and Bone Strength: A Randomized Clinical Trial." JAMA 322(8):736–745. DOI: 10.1001/jama.2019.11889. PMID: 31454046. ClinicalTrials.gov NCT01900860. (Three years, double-blind, single centre, Calgary; 311 healthy adults aged 55–70 without osteoporosis, baseline 25(OH)D 30–125 nmol/L; 400 IU n=109, 4,000 IU n=100, 10,000 IU n=102; 287 completed. Co-primary outcomes total volumetric BMD at radius and tibia by HR-pQCT and estimated failure load. 4,000 and 10,000 IU produced significantly lower radial BMD than 400 IU; tibial BMD was lower only at 10,000. Hypercalciuria 17%, 22%, 33% (19/109, 22/100, 34/102), dose-response p=.006; hypercalcemia dose-response p=.005, all episodes mild and resolving. Estimated bone strength (failure load) did not differ significantly between groups, and the authors treat the density findings as hypothesis-generating rather than as demonstrated skeletal harm. Notes that 3% of US adults report intakes of at least 4,000 IU/day. Source note: a prespecified secondary safety analysis of the same study, Billington, E.O., et al. (2020), Journal of Clinical Endocrinology & Metabolism, PMID 31746327, reports hypercalciuria as 17%, 22% and 31% across the same three arms. That paper analyses 373 participants rather than the 311 of the main cohort, which is why the third figure differs. The body uses the main-cohort figures cited here. Recorded so the discrepancy is not mistaken for an error in either direction.)

  7. Manson, J.E., Cook, N.R., Lee, I-M., et al. (2019). "Vitamin D Supplements and Prevention of Cancer and Cardiovascular Disease." New England Journal of Medicine 380(1):33–44. DOI: 10.1056/NEJMoa1809944. PMID: 30415629. PMCID: PMC6425757. NCT01169259. (25,871 randomized; 2×2 factorial with marine omega-3; 2,000 IU/day D3; men ≥50 and women ≥55; 5,106 African American participants. Both primary endpoints, invasive cancer of any type and major cardiovascular events, were not reduced. Participants agreed to limit other supplemental vitamin D to 800 IU/day. Funded by NIH and others.)

  8. Neale, R.E., Baxter, C., Romero, B.D., et al. (2022). "The D-Health Trial: a randomised controlled trial of the effect of vitamin D on mortality." The Lancet Diabetes & Endocrinology 10(2):120–128. DOI: 10.1016/S2213-8587(21)00345-4. PMID: 35026158. ACTRN12613000743763. (21,315 Australians aged 60 and over, unscreened and largely replete; 60,000 IU monthly or placebo for five years; all-cause mortality not reduced. Authors invoked the precautionary principle in suggesting this regimen be avoided despite its compliance advantage until the question is resolved.)

  9. Tripkovic, L., Lambert, H., Hart, K., Smith, C.P., Bucca, G., Penson, S., Chope, G., Hypponen, E., Berry, J., Vieth, R., Lanham-New, S. (2012). "Comparison of vitamin D2 and vitamin D3 supplementation in raising serum 25-hydroxyvitamin D status: a systematic review and meta-analysis." American Journal of Clinical Nutrition 95(6):1357–1364. PMID: 22552031. PMCID: PMC3349454. (Random-effects mean difference favouring D3 of 15.23, 95% CI 6.12–24.34, p=0.001. Significant for bolus dosing, p=0.0002; effect lost with daily supplementation. The authors' own later commentary records high heterogeneity between studies and insufficient statistical power to be conclusive.)

  10. Grossmann, R.E., Tangpricha, V. (2010). "Evaluation of vehicle substances on vitamin D bioavailability: a systematic review." Molecular Nutrition & Food Research 54(8):1055–1061. DOI: 10.1002/mnfr.200900578. PMID: 20425758. (Three oil-vehicle studies, two lactose or cellulose powder, one ethanol. Oil produced the greatest mean rise in 25(OH)D. Authors conclude future studies should examine bioavailability across vehicles and in populations with fat malabsorption, i.e. they did not regard the question as settled.)

  11. Dawson-Hughes, B., Harris, S.S., Palermo, N.J., Ceglia, L., Rasmussen, H. (2013). "Meal conditions affect the absorption of supplemental vitamin D3 but not the plasma 25-hydroxyvitamin D response to supplementation." Journal of Bone and Mineral Research 28(8):1778–1783. DOI: 10.1002/jbmr.1896. PMID: 23427007. Free article. (62 healthy older men and women randomized to no meal, high-fat meal or low-fat meal with a monthly 50,000 IU dose, followed 90 days. Mean 12-hour vitamin D3 increments 200.9 nmol/L no meal, 207.4 high-fat, 241.1 low-fat, p=0.038, the low-fat group significantly higher than both others. Increments in 25(OH)D at 30 and 90 days did not differ between groups.)

  12. Dawson-Hughes, B., Harris, S.S., Lichtenstein, A.H., Dolnikowski, G., Palermo, N.J., Rasmussen, H. (2015). "Dietary fat increases vitamin D-3 absorption." Journal of the Academy of Nutrition and Dietetics 115(2):225–230. (Same research group, opposite direction on the absorption step. Cited deliberately alongside reference 11 rather than in place of it: the fat question is unsettled within a single group's own work, which is the point the body text makes.)

  13. Cavalier, E., Lukas, P., Crine, Y., Peeters, S., Carlisi, A., Le Goff, C., Gadisseur, R., Delanaye, P., Souberbielle, J.C. (2016). "A Randomised, Cross-Over Study to Estimate the Influence of Food on the 25-Hydroxyvitamin D3 Serum Level after Vitamin D3 Supplementation." Nutrients 8(5):309. (88 subjects, single 50,000 IU dose fully solubilised in an oily solution, taken fasting or with a standardised high-fat breakfast; 25(OH)D3 assessed at 3, 5, 7, 14, 30 and 60 days; no significant difference. Open access.)

  14. Diederichsen, A.C.P., Lindholt, J.S., Möller, S., et al. (2022). "Vitamin K2 and D in Patients With Aortic Valve Calcification: A Randomized Double-Blinded Clinical Trial" (AVADEC). Circulation 145(18):1387–1397. DOI: 10.1161/CIRCULATIONAHA.121.057008. PMID: 35465686. NCT03243890. (365 men randomized per the primary report, community-dwelling Danish men recruited from the DANCAVAS screening trial, aged 65–74, with aortic valve calcification score ≥300 AU as stated in the paper's methods and >300 AU as stated in its abstract; MK-7 720 µg plus vitamin D3 25 µg daily or placebo for 24 months. The primary analysis did not establish a significant reduction in progression, and although dp-ucMGP fell significantly, the calcification score and echocardiographic measures were unaffected. Source note: the trial's own secondary analysis, reference 15, states that 389 participants were randomized. The discrepancy is between two publications from the same investigators, not between a paper and a summary of it. This article follows the primary report. Recorded so the figure is not "corrected" in either direction without knowing why the two differ. One author has served on a Generally Recognized as Safe panel reviewing the safety of vitamin K2 for use in foods in the United States, disclosed in reference 15.)

  15. "Effects of Vitamin K2 and D Supplementation on Coronary Artery Disease in Men: A Randomized Controlled Trial." JACC: Advances (2023). DOI: 10.1016/j.jacadv.2023.100643. (Prespecified secondary analysis; 304 participants without ischaemic heart disease; numerically smaller increase in coronary calcification, between-group difference not statistically significant.)

  16. Bartstra, J.W., Draaisma, F., Zwakenberg, S.R., Lessmann, N., Wolterink, J.M., van der Schouw, Y.T., et al. (2021). "Six months vitamin K treatment does not affect systemic arterial calcification or bone mineral density in diabetes mellitus 2." European Journal of Nutrition 60:1691–1699. DOI: 10.1007/s00394-020-02412-z. PMID: 33068157. PMCID: PMC7987615. (Vitamin K2 reduced circulating inactive matrix Gla protein but did not halt arterial calcification on 18F-NaF PET and CT; post-hoc analysis extended this to systemic CT-measured arterial calcification and spinal bone mineral density.)

  17. Li, T., Wang, Y., Tu, W-P. (2023). "Vitamin K supplementation and vascular calcification: a systematic review and meta-analysis of randomized controlled trials." Frontiers in Nutrition 10:1115069. DOI: 10.3389/fnut.2023.1115069. PMID: 37252246. PMCID: PMC10218696. (14 RCTs, 1,842 enrolled and 1,533 analysed overall. Five trials measured CAC change; one excluded for incompatible reporting, leaving four trials and 424 participants in the pooled CAC analysis: MD −17.37, 95% CI −34.18 to −0.56, p=0.04, I²=34%. Seven trials and 578 participants showed reduced dp-ucMGP, MD −243.31, p=0.0001, I²=71%; six trials and 547 participants showed no significant difference in adverse events. The review also records that eight other trials measuring major arterial or valve calcification reported no appreciable benefit, and its authors state that vitamin K's role in CAC seems to remain controversial. Trials varied in vitamin K form, dose, population, disease state and imaging endpoint. Authors declare no commercial or financial conflict of interest.)

  18. "Effects of vitamin K supplementation on vascular calcification in chronic kidney disease: A systematic review and meta-analysis of randomized controlled trials." Frontiers in Nutrition. DOI: 10.3389/fnut.2022.1001826. (Ten RCTs, 733 CKD patients; serum biomarkers decreased and vascular elasticity improved mildly, but no significant change in calcification scores derived from radiological examination; authors conclude solid evidence for a protective effect in CKD is still lacking. Half the included studies were judged low risk of bias.)

  19. Knapen, M.H.J., Drummen, N.E., Smit, E., Vermeer, C., Theuwissen, E. (2013). "Three-year low-dose menaquinone-7 supplementation helps decrease bone loss in healthy postmenopausal women." Osteoporosis International 24(9):2499–2507. DOI: 10.1007/s00198-013-2325-6. PMID: 23525894. (244 healthy postmenopausal women; MK-7 180 µg/day or placebo for three years; slowed decline at some skeletal sites. Does not establish that vitamin D supplementation universally requires K2.)

  20. Dai, Q., Zhu, X., Manson, J.E., Song, Y., Li, X., Franke, A.A., Costello, R.B., Rosanoff, A., Nian, H., Fan, L., Murff, H., Ness, R.M., Seidner, D.L., Yu, C., Shrubsole, M.J. (2018). "Magnesium status and supplementation influence vitamin D status and metabolism: results from a randomized trial." American Journal of Clinical Nutrition 108(6):1249–1258. DOI: 10.1093/ajcn/nqy274. PMID: 30541089. (180 participants aged 40–85, twelve weeks, magnesium and placebo doses customised to baseline dietary intake; ancillary study nested within the Personalized Prevention of Colorectal Cancer Trial. Magnesium raised 25(OH)D3 when baseline 25(OH)D was below roughly 30 ng/mL and lowered it when baseline was approximately 30–50 ng/mL, interactions surviving Bonferroni correction. Limitations to note: outcome is vitamin D metabolism, not a clinical endpoint, and participants had a history of colorectal adenomas or polyps and are not representative of the general population.)

  21. Zhou, et al. (2022). "A narrative review of vitamin K forms in cheese and their potential role in cardiovascular disease." International Journal of Dairy Technology. DOI: 10.1111/1471-0307.12901. (K1 synthesised by plants, primarily in green leafy vegetables and plant oils; vitamin K2 other than MK-4 bacterially synthesised and found in fermented foods; MK-4 formed through animal tissue conversion, mainly in meat, liver and egg yolk. Narrative rather than systematic review.)

  22. "Content and Bioaccessibility of Vitamin K (Phylloquinone and Menaquinones) in Cheese." Foods (2021). PMCID: PMC8700448. (Eight cheese products differing in ripening time, starter culture, fat and water content; vitamin K content from under 0.5 to 32 µg/100 g, bioaccessibility 6.4% to 80% using the INFOGEST 2.0 in vitro model; longer ripening did not necessarily increase menaquinones. In vitro bioaccessibility, not human absorption. Cheese samples supplied by a commercial dairy company; weigh accordingly.)

  23. Sanders, K.M., Stuart, A.L., Williamson, E.J., Simpson, J.A., Kotowicz, M.A., Young, D., Nicholson, G.C. (2010). "Annual high-dose oral vitamin D and falls and fractures in older women: a randomized controlled trial." JAMA 303(18):1815–1822. DOI: 10.1001/jama.2010.594. PMID: 20460620. (Double-blind, placebo-controlled; 2,256 community-dwelling women aged 70 and over at high risk of fracture; single annual oral dose of 500,000 IU cholecalciferol in autumn or winter. Falls incidence rate ratio 1.15, 95% CI 1.02–1.30, p=.03, from 2,892 falls against 2,512. Fracture incidence rate ratio 1.26, 95% CI 1.00–1.59, p=.047, 171 fractures against 135. Post-hoc temporal analysis: falls IRR 1.31 in the first three months after dosing against 1.13 in the following nine. A published correction appears separately at JAMA 2010;303(23):2357; the issue-23 entry that circulates in some databases refers to that correction, not to the original article.)

  24. Intestinal absorption of vitamin D: a systematic review. Nutrition Reviews 76(1):60–76. PMID: 29025082. (46 of 2,069 identified articles met inclusion criteria. Vitamin D was better absorbed with fat-containing meals, but absorption also occurred without fat or oily vehicles. Concludes absorption is probably by passive diffusion plus a mechanism involving membrane carriers, especially cholesterol transporters, with data still scarce, and that factors modifying cholesterol absorption also alter vitamin D absorption. Added at v6: the v5 sentence stated that vitamin D3 must be emulsified and carried in micelles before uptake, which is the classical account stated more absolutely than this review supports. Found while researching the Supplementation article and corrected under the fix-errors-as-they-arise rule.)

Sourcing note: this article cites randomized controlled trials, systematic reviews, clinical practice guidelines and government reference documents with DOI/PMID where available, and prefers primary trial reports over summaries of them. Sample sizes, designs, primary endpoints, funding and null results are stated in the reference notes rather than left implicit, and failed primary endpoints are stated plainly in the body rather than only in the notes. Where a widely repeated claim rests on mechanism rather than outcome, the article says so; where two studies from the same research group disagree, both are cited. Every reference was verified against an openly accessible source before the claim resting on it was written, and no bibliographic red flags remain. This article makes no recommendation, provides no dose, protocol or regimen for the reader, and discusses no supplement product, by editorial policy; doses appearing in the text are the doses trials administered. Cross-link targets (#) resolve once the site structure is live. Reading time is measured, not asserted: body words excluding the reference list and the metadata header, counted at 225 words per minute and rounded to the nearest minute.

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