With thiazide diuretics
Safety flag
Combined use can increase hypercalcemia risk, particularly with high-dose vitamin D or impaired kidney function.
Interaction evidence source All research profiles
Vitamin / bone health
Vitamin D
Prepared by the ezGLP team. Sources last checked . Profile reviewed .
Also known as Cholecalciferol, Vitamin D3, Ergocalciferol, Vitamin D2
Routes represented in the knowledgebase: Oral.
Educational overview
Supplement and prescription forms exist; excessive intake can cause hypercalcemia, kidney injury, soft-tissue calcification, and arrhythmias.
Vitamin D is a fat-soluble secosteroid that behaves as a prohormone rather than a classical vitamin. Skin synthesises cholecalciferol (vitamin D3) from 7-dehydrocholesterol under ultraviolet B light, while ergocalciferol (vitamin D2) is produced from irradiated yeast and fungi. Either form is hydroxylated in the liver to 25-hydroxyvitamin D, the circulating metabolite measured in blood tests, and then in the kidney to the active hormone 1,25-dihydroxyvitamin D, which binds the vitamin D receptor and drives intestinal calcium and phosphate absorption and bone mineralisation. Deficiency causes rickets in children and osteomalacia in adults. Supplements contain D3 or D2, and D3 generally raises serum 25-hydroxyvitamin D more efficiently.
Vitamin D has been tested in some of the largest nutrition trials ever conducted, and the results for their primary endpoints were largely null. VITAL randomised nearly 26,000 United States adults and, as reported in the New England Journal of Medicine in 2019, found no reduction in invasive cancer or in major cardiovascular events; a 2022 report from the same trial found no reduction in fractures. The Australian D-Health Trial randomised more than 21,000 older adults to monthly high-dose vitamin D and reported no reduction in all-cause mortality in Lancet Diabetes and Endocrinology in 2022. Benefit remains clear for preventing and correcting deficiency states such as rickets and osteomalacia.
Regulation follows the amount and the claim. Oral vitamin D at nutrient levels is a dietary supplement in the United States and a food supplement in the European Union, and it is added to milk, infant formula, and other fortified foods. Higher-strength ergocalciferol capsules are prescription drugs cleared under abbreviated new drug applications, although their labelled indications are hypoparathyroidism, refractory rickets, and familial hypophosphatemia rather than ordinary deficiency, and the label warns that the range between therapeutic and toxic amounts is narrow. No injectable cholecalciferol product is approved in the United States; the approved parenteral vitamin D drugs are the activated analogues calcitriol, doxercalciferol, and paricalcitol.
Vitamin D is degraded by air and light, so capsules, softgels, and drops are kept in the closed original container away from heat and light, with liquid products following their labelled after-opening period. Because the vitamin is fat-soluble and stored in adipose tissue, an excess accumulates rather than being excreted, and NIH describes toxicity as almost always arising from supplements, including manufacturing errors and mistaken administration. For a dose log or inventory record, the useful fields are the form (D3 or D2), the strength in international units, the product type, and every other contributing source, since multivitamins, calcium combinations, and fortified foods add up. Serum 25-hydroxyvitamin D and calcium results dated against the log reveal accumulation.
- Category
- Vitamin / bone health
- Routes represented
- Oral
- Storage context
- Follow the product label; store in the original container away from excess heat and moisture.
Published literature
No verified PubMed or DOI link is available for this entry.
Safety evidence
Serious or important: hypercalcemia, kidney stones or failure, soft-tissue calcification, arrhythmia.
These effects are associated with excessive exposure.
Safety evidence sourceInteraction evidence
These are general, pairwise evidence notes. Green identifies the potential-synergy category, while Lv3/Lv2/Lv1 communicates evidence strength; it does not guarantee benefit or cancel a safety warning.
With magnesium
Complementary evidenceLv3
A randomized human trial found magnesium plus vitamin D increased serum vitamin D status more than vitamin D alone.
Interaction evidence sourceRelated trial analysisNIH magnesium overviewCommon questions
What did the VITAL and D-Health trials find about vitamin D?
Both were large randomised placebo-controlled trials and both were largely null on their primary endpoints. VITAL, in nearly 26,000 United States adults, found no reduction in invasive cancer or major cardiovascular events over roughly five years, and a later analysis found no reduction in fractures. D-Health, in more than 21,000 older Australians receiving monthly high-dose vitamin D, found no reduction in all-cause mortality. Neither trial selected participants for deficiency.
Can vitamin D be toxic?
Yes. Because it is fat-soluble and stored, sustained excessive intake raises serum 25-hydroxyvitamin D and produces hypercalcemia, with nausea, vomiting, weakness, excessive thirst, and kidney stones, and in extreme cases kidney failure, soft-tissue calcification, arrhythmias, and death. The NIH Office of Dietary Supplements notes that toxicity almost always originates from supplements, including manufacturing errors and mistaken administration, and that sun exposure is not considered a cause.
What is the difference between vitamin D2 and D3?
Vitamin D2, ergocalciferol, is produced from irradiated yeast and fungi; vitamin D3, cholecalciferol, is made in skin under ultraviolet B light and obtained from oily fish and other animal sources. Both travel the same hydroxylation pathway, but studies generally find D3 raises and maintains serum 25-hydroxyvitamin D more efficiently. High-strength prescription capsules in the United States contain D2, while most over-the-counter supplements contain D3.
Is there an FDA-approved vitamin D injection?
Not for nutritional vitamin D. No injectable cholecalciferol or ergocalciferol product is approved in the United States. The approved parenteral vitamin D drugs are the activated analogues calcitriol, doxercalciferol, and paricalcitol, indicated for secondary hyperparathyroidism in chronic kidney disease. Injectable cholecalciferol ampoules are marketed in some other countries, and higher-strength oral ergocalciferol capsules are prescription products in the United States.
Who is most likely to be low in vitamin D?
NIH lists breastfed infants without supplementation, older adults, people with little sun exposure or with darker skin pigmentation, people with fat malabsorption from celiac disease, Crohn's disease, or bariatric surgery, and people with obesity, in whom the vitamin is sequestered in adipose tissue. Medicines including orlistat, some statins, corticosteroids, and certain anticonvulsants also lower vitamin D concentrations.
Further reading
- NIH Office of Dietary Supplements, Vitamin D fact sheet for health professionals
- Manson et al., VITAL trial, cancer and cardiovascular disease, N Engl J Med 2019
- LeBoff et al., VITAL trial, incident fractures, N Engl J Med 2022
- Neale et al., D-Health Trial, mortality, Lancet Diabetes Endocrinol 2022
- DailyMed, Ergocalciferol Capsules USP label
- MedlinePlus health topic, Vitamin D
Summarised from published literature for reference only, with citations to the source. Evidence is graded as reported and is not a recommendation to combine, dose, or use any compound.
For personal tracking and education only. Not medical advice, diagnosis, or treatment, and not a medical device. Peptides may be prescription-only or unapproved where you live. Consult a licensed healthcare professional.