Vitamin D3 (Cholecalciferol)
vitamin · also known as Cholecalciferol, Vitamin D
This is general information, not medical advice. Supplements can interact with medicines and health conditions. Always check with your doctor or pharmacist before starting or changing supplements.
What it is
Vitamin D3 (cholecalciferol) is a fat-soluble vitamin the body produces in skin exposed to UVB sunlight and also obtains from diet and supplements. It is converted in the liver and kidneys into its active hormone form, which regulates calcium and phosphate absorption and is essential for bone mineralisation, and also has roles in immune and muscle function. Many people living at higher latitudes, with limited sun exposure, darker skin, or who are older have low vitamin D status, which is why supplementation is common. People take vitamin D3 mainly to correct deficiency and support bone health; evidence for other benefits, such as reduced infections, is weaker and depends heavily on baseline vitamin D status and dosing pattern. Because it is fat-soluble, it can accumulate in the body if taken in excess over long periods, unlike water-soluble vitamins that are readily excreted.
Evidence-based benefits
- Grade B· Limited evidence[1]
In people with inadequate vitamin D intake, supplementation at 700-800 IU/day reduces the risk of hip and other nonvertebral fractures in older adults, though lower doses (400 IU/day) are not effective.
A meta-analysis of randomised controlled trials found 700-800 IU/day of vitamin D reduced hip fracture risk by about 26% and nonvertebral fracture risk by about 23% versus comparators, with no benefit seen at 400 IU/day. The trials pooled were mostly in older, likely vitamin-D-insufficient populations; more recent large trials in vitamin-D-replete general populations have found smaller or no fracture benefit, so the effect appears to depend on baseline status.
- Grade B· Limited evidence[1]
Daily or weekly vitamin D supplementation modestly reduces the risk of acute respiratory tract infections; large intermittent bolus doses do not show this benefit.
An individual-participant-data meta-analysis of 25 randomised controlled trials (10,933 participants) found vitamin D supplementation reduced acute respiratory infection risk overall (adjusted odds ratio 0.88), with protection concentrated in people receiving daily or weekly dosing and no protection in those receiving large intermittent bolus doses. Subsequent larger meta-analyses have found smaller or non-significant overall effects, so the benefit is modest and dosing-regimen dependent.
- Grade B· Limited evidence[1]
Daily vitamin D3 at medium doses (roughly 1,600-3,200 IU/day) may reduce fall risk in older adults; this benefit does not extend to higher daily doses.
A randomised clinical trial in older adults found daily vitamin D3 at medium doses (1600-3200 IU/day) decreased the incidence of falls compared with lower and higher doses, describing a U-shaped dose-response relationship rather than a simple "more is better" effect.
Risks & contraindications
- Grade B· Limited evidence[1]
Sustained high-dose vitamin D3 supplementation (well above typical over-the-counter doses, sustained for months) can cause hypercalcemia.
A secondary analysis of a randomised controlled trial testing escalating high-dose vitamin D3 regimens found dose-dependent increases in serum calcium, with hypercalcemia occurring at the highest doses tested. Typical over-the-counter supplemental doses (up to a few thousand IU/day) were not associated with this risk in the trial.
- Grade B· Limited evidence[1]
High daily vitamin D3 doses (roughly 4,000-4,800 IU/day and above) do not provide additional fall protection compared with medium doses and may increase fall risk.
In the same randomised trial comparing vitamin D3 dose levels, older adults assigned to the highest daily doses tested had more falls than those assigned medium doses, despite achieving higher serum 25(OH)D levels -- underscoring that higher doses are not automatically safer or more effective.
Dosage & how to take it
- Cholecalciferol (D3): 1000–4000 iu/day, any time of day, with food. Take with a meal containing fat to improve absorption. Doses at the upper end of this range (2,000-4,000 IU/day) are typically reserved for correcting documented deficiency or for people with malabsorption or very limited sun exposure; large intermittent bolus dosing (e.g., 50,000 IU/month) is a distinct, clinician-directed regimen not covered by this range.
Interactions
Bile acid sequestrants like cholestyramine work by binding bile acids in the gut, and your body needs those same bile acids to absorb fat-soluble vitamins such as vitamin D. A clinical reference on this drug class specifically names vitamin D among the fat-soluble vitamins it can deplete, recommending vitamins be taken a full 4 hours before the sequestrant dose; a separate clinical reference on cholestyramine specifically gives the more general rule of spacing other oral substances 1 hour before or 4 hours after it. Rather than track two slightly different windows, the safest and simplest instruction is to keep a full 4-hour gap between your vitamin D3 dose and your sequestrant dose, on either side. A 1978 case report of osteomalacia (bone softening from vitamin D deficiency) in a patient on cholestyramine illustrates the risk in practice, though that patient had also had ileal surgery, which independently impairs vitamin D absorption, so it doesn't isolate cholestyramine's effect on its own. If you take a sequestrant long-term, ask your doctor about periodic vitamin D level checks.
Take at least 4h apart from Bile acid sequestrants.
Tenofovir disoproxil (the TDF in this combination) can gradually lower bone mineral density, likely by affecting how the kidneys handle phosphate and vitamin D metabolism. Supplementing vitamin D3 alongside calcium has been studied specifically as a countermeasure: a randomised controlled trial in people on TDF/emtricitabine/efavirenz found vitamin D and calcium supplementation reduced the bone loss seen with TDF-based therapy, and a systematic review and meta-analysis across both HIV treatment and PrEP populations reached the same conclusion. If you are taking this medication long-term (including for PrEP), talk to your prescriber about adding vitamin D3 (with calcium) to help protect your bone density; this is a supportive pairing, not a risk.
Our medication coverage is not exhaustive. Absence of a warning here is not evidence of safety. Always confirm with your pharmacist.
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