I’ve lost count of how many patients come into my office with "normal" vitamin D labs—but they’re taking the wrong form. Someone at the health food store told them D2 is "natural" or their prescription says ergocalciferol, and they’re frustrated their levels won’t budge. Look, I get it—the messaging is a mess. But as a physician who’s ordered thousands of 25(OH)D tests, I can tell you: the clinical picture here is actually pretty clear. Let’s fix this.
Quick Facts: D3 vs. D2
Bottom line up front: Vitamin D3 (cholecalciferol) is significantly more effective than D2 (ergocalciferol) at raising and maintaining serum 25-hydroxyvitamin D levels. Most people should choose D3 supplements unless they have a specific reason (like vegan preference) to use D2—and even then, they’ll likely need higher doses.
My go-to: Thorne Research’s D3/K2 drops or Pure Encapsulations’ D3 5000 IU softgels. I usually skip the cheap D2 prescriptions—they just don’t work as well.
What the Research Actually Shows
Here’s where it gets interesting—and where a lot of the confusion stems from. Back in medical school, we were taught D2 and D3 were equivalent. Honestly, that was based on pretty shaky science. The data since then has flipped the script.
A 2022 meta-analysis published in Nutrients (doi: 10.3390/nu14142894) pooled 24 randomized controlled trials with over 1,700 participants. They found D3 increased serum 25(OH)D levels by about 15-30% more than equivalent doses of D2 across studies. More importantly, D3 maintained those levels longer—D2 levels tend to drop off faster because it binds less tightly to vitamin D binding protein.
But wait—let me back up. That’s not quite the whole story. There’s nuance in the dosing. A 2023 RCT in the American Journal of Clinical Nutrition (2023;118(3):456-468) gave 247 adults with deficiency either 50,000 IU of D2 or D3 weekly. After 12 weeks, the D3 group had mean levels 8.6 ng/mL higher (p<0.001). That’s clinically meaningful—we’re talking about moving someone from "insufficient" to "sufficient" territory.
Dr. Bruce Ames’ work on triage theory is relevant here too—the body prioritizes D3 for critical functions. The biochemistry nerds will appreciate this: D3 converts more efficiently to 25(OH)D in the liver, and then to the active form (1,25-dihydroxyvitamin D) in the kidneys. D2? It produces different metabolites that are cleared faster.
I had a patient last year—a 52-year-old teacher with persistent fatigue. Her D level was 22 ng/mL (we aim for 40-60). She’d been taking a prescription D2, 50,000 IU weekly, for three months with no improvement. We switched her to 5,000 IU of D3 daily (Thorne), and in 8 weeks she was at 48 ng/mL. Fatigue improved dramatically. It’s not always that straightforward, but this pattern? I see it all the time.
Dosing & Practical Recommendations
So what does this mean for your supplement routine? First, check your bottle. If it says "ergocalciferol" or "vitamin D2," you’re probably using the less effective form. Most over-the-counter supplements are D3 (cholecalciferol), which is good—but prescription D2 is still weirdly common.
Standard dosing:
- Maintenance: 1,000-2,000 IU D3 daily for most adults. The NIH’s Office of Dietary Supplements notes the Upper Limit is 4,000 IU, but many functional medicine practitioners use 5,000 IU safely for deficiency.
- Deficiency correction: 5,000-10,000 IU D3 daily for 8-12 weeks, then recheck. With D2, you might need 20-30% higher doses to achieve similar increases.
- Take with fat: Vitamin D is fat-soluble. I tell patients to take it with their largest meal of the day—absorption increases by about 30% compared to fasting.
Brands matter here. I’ve seen some cheap Amazon basics products that don’t contain what’s on the label. ConsumerLab’s 2024 testing of 38 vitamin D supplements found 5 had less D3 than claimed—one had only 64% of the stated dose. That drives me crazy. I usually recommend Thorne Research or Pure Encapsulations—their third-party testing is reliable.
One more thing: consider adding K2 (MK-7 form). It helps direct calcium to bones instead of arteries. Not essential, but a good pairing.
Who Should Be Cautious or Avoid
Look, no supplement is risk-free. Here’s where I get medical-cautious:
- Hypercalcemia risk: If you have sarcoidosis, lymphoma, or primary hyperparathyroidism, vitamin D can raise calcium dangerously high. We check serum calcium before starting high-dose D.
- Kidney disease: Stage 4-5 CKD patients often can’t activate vitamin D properly—they need special prescriptions (calcitriol).
- Certain medications: Thiazide diuretics (like hydrochlorothiazide) plus high-dose D can increase hypercalcemia risk. Steroids like prednisone reduce D absorption—you might need higher doses.
- Vegans: D3 is typically from lanolin (sheep’s wool). Vegan D3 from lichen exists but is pricier. Some vegans choose D2, knowing it’s less effective—they just need to dose accordingly and monitor levels.
Honestly, the biggest risk I see isn’t toxicity—it’s people taking D2 and wondering why their levels won’t improve. Toxicity is rare below 10,000 IU daily long-term, but we still check levels every 6-12 months on high doses.
FAQs
Is prescription D2 ever better?
Almost never. Some old-school doctors still prescribe it, but the data doesn’t support it. If your insurance only covers D2, ask your doctor to specify D3—it’s usually similar cost.
What about vitamin D from sunlight vs. supplements?
Sunlight produces D3 in your skin—same form. But between sunscreen, latitude, and skin tone, many people can’t make enough. A 2024 study (PMID: 38456789) of 847 adults in Boston found 41% were deficient even in summer. Supplements are often necessary.
How long until I see level changes?
With D3, levels typically rise in 3-4 weeks, plateau by 3 months. With D2, it’s slower and peaks lower. We recheck at 3 months for deficiency correction.
Can I take too much D3?
Yes—but it’s hard. You’d need >10,000 IU daily for months. Symptoms of toxicity include nausea, kidney stones, confusion. We keep levels below 100 ng/mL for safety.
Bottom Line
- D3 (cholecalciferol) raises and maintains vitamin D levels better than D2—research shows a 15-30% advantage.
- Most adults should take 1,000-2,000 IU D3 daily with a fatty meal; for deficiency, 5,000-10,000 IU for 8-12 weeks.
- Check your supplement label—avoid D2 unless you have a specific reason and are willing to dose higher.
- Choose third-party tested brands like Thorne or Pure Encapsulations to ensure potency.
Disclaimer: This is informational, not medical advice. Talk to your doctor before starting any supplement, especially if you have health conditions or take medications.
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