Vitamin D3
Cholecalciferol — the form your skin makes from sunlight
Unregulated by FDA
for efficacy/purity
Version 2025-04 · Last Reviewed April 1, 2025
About this review (v2025-04, last reviewed April 1, 2025): This review was compiled from peer-reviewed clinical trials, independent laboratory analyses, and regulatory filings. Supplement manufacturers had no editorial input. Funding sources for cited studies are disclosed where available. Read our full methodology
This content is for educational purposes only. Supplements are not FDA-approved to treat, cure, or prevent any disease. Discuss supplementation with your healthcare provider before starting, especially if you take medications.
What it is
A fat-soluble secosteroid hormone precursor. The body produces vitamin D3 in the skin when UVB light converts 7-dehydrocholesterol to previtamin D3. It is then converted in the liver to 25-OH vitamin D (the storage form measured in blood tests) and in the kidneys to 1,25-OH vitamin D (the active hormone). Nearly every cell in the body has vitamin D receptors.
Why form matters
D3 (cholecalciferol) raises serum 25-OH vitamin D levels approximately 87% more effectively than D2 (ergocalciferol) and sustains those levels longer. The K2 co-supplementation question — whether D3 should be taken with vitamin K2 to properly direct calcium to bones rather than arteries — is biologically well-reasoned and the MK-7 form of K2 matters more than MK-4 due to its longer half-life.
Molecular Forms — What the Research Actually Used
The form in the bottle determines how much actually reaches your bloodstream.
Absorption: Reference standard
The form your skin makes. Raises 25-OH D ~87% more effectively than D2. Fat-soluble — absorbs best with dietary fat. Oil-based softgels outperform dry tablets significantly.
Absorption: D3 reference + K2 enhanced routing
K2 as MK-7 (half-life ~72 hrs) activates matrix Gla protein, which redirects calcium absorbed via D3 into bones and away from arteries. Biologically rational combination, especially at higher D3 doses.
Absorption: ~46% less effective than D3
Plant-derived. Used in many prescription vitamin D products and fortified foods. Less potent and shorter-acting than D3. Choose D3 unless D2 is specifically prescribed.
Absorption: Very high — bypasses liver step
Used clinically in patients with liver disease or malabsorption. Rarely available in standard OTC supplements. Not necessary for most people.
Dosing — What the Research Used
Deficiency prevention (adults, no testing)
Endocrine Society / Holick 2011
Correcting confirmed deficiency (25-OH D < 20 ng/mL)
Holick et al. — under physician guidance
Maintenance after repletion
Most adults stabilize adequately at this dose
Co-supplementing with K2 (MK-7)
MK-7 half-life advantage over MK-4 (~72 hrs vs ~4 hrs)
Upper tolerable limit (not a target)
NIH Office of Dietary Supplements
Note: Testing serum 25-OH vitamin D before supplementing allows dosing to be guided by actual need rather than assumption. Most labs flag deficiency at < 20 ng/mL and insufficiency at 20–29 ng/mL. The 'optimal' range is debated — the VITAL trial used 2,000 IU/day in adults not selected for deficiency and found no cardiovascular or cancer incidence benefit.
Frequently Asked Questions About Vitamin D3
- What is Vitamin D3?
- A fat-soluble secosteroid hormone precursor. The body produces vitamin D3 in the skin when UVB light converts 7-dehydrocholesterol to previtamin D3. It is then converted in the liver to 25-OH vitamin D (the storage form measured in blood tests) and in the kidneys to 1,25-OH vitamin D (the active hormone). Nearly every cell in the body has vitamin D receptors.
- What does Vitamin D3 do?
- Vitamin D deficiency affects an estimated 40% of American adults by standard 25-OH D thresholds. The landmark VITAL trial (25,871 participants, 5 years) found 2,000 IU/day D3 did not reduce cancer incidence or cardiovascular events in well-nourished adults — but did significantly reduce cancer mortality (HR 0.83). Most positive evidence for D3 supplementation is in demonstrably deficient individuals. Testing serum 25-OH D before and after supplementing is the rational approach.
- What is the typical dose of Vitamin D3?
- Testing serum 25-OH vitamin D before supplementing allows dosing to be guided by actual need rather than assumption. Most labs flag deficiency at < 20 ng/mL and insufficiency at 20–29 ng/mL. The 'optimal' range is debated — the VITAL trial used 2,000 IU/day in adults not selected for deficiency and found no cardiovascular or cancer incidence benefit.
- Does Vitamin D3 interact with any medications?
- Vitamin D3 has known interactions with: Corticosteroids (prednisone) — Corticosteroids impair vitamin D activation and reduce intestinal calcium absorption. Long-term use substantially depletes vitamin D and accelerates bone loss. Supplementation is commonly recommended alongside long-term steroids.; Thiazide diuretics — Thiazides reduce urinary calcium excretion. Combined with high-dose vitamin D (which increases calcium absorption), this may cause hypercalcemia. Monitor serum calcium at high D3 doses.; Orlistat — Blocks fat absorption, reducing vitamin D bioavailability by up to 30%. Time vitamin D away from orlistat doses.; Statins (via CYP3A4) — Some evidence that vitamin D status influences statin metabolism. Association only — not a clinical concern at standard doses..
- Who should be cautious about taking Vitamin D3?
- Exercise caution or consult a healthcare provider if you are: Granulomatous diseases (sarcoidosis, tuberculosis, lymphoma) — endogenous overactivation of vitamin D causes hypercalcemia risk even at normal supplement doses; Primary hyperparathyroidism — dysregulated calcium metabolism; vitamin D may worsen hypercalcemia; Kidney disease (stage 3+) — impaired conversion of 25-OH D to active hormone; requires medical supervision and possible prescription calcifediol; Patients on thiazide diuretics at high D3 doses — hypercalcemia monitoring advised.
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