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Key takeaways
Vitamin D2 (ergocalciferol) is derived from plant sources and commonly found in fortified foods, while Vitamin D3 (cholecalciferol) comes from animal sources and is produced by the skin when exposed to sunlight.
The liver processes vitamin D2 and D3 into the active metabolite calcitriol, which is crucial for bone health and immune function.
Studies have shown that vitamin D3 supplements may be more effective than D2 in raising the blood levels of calcifediol, the precursor to calcitriol.
Both vitamin D2 and D3 are used to treat vitamin D insufficiency and support overall health, but vitamin D3 may contribute more significantly to vitamin D stores in the body.
Differences | Similarities | Conditions treated | Efficacy | Insurance coverage and cost comparison | Side effects | Drug interactions | Warnings | FAQs
The D vitamins are fat-soluble vitamins that play an important role in calcium absorption and bone health, as well as immune function. Our skin produces vitamin D when exposed to sunlight, but due to the skin cancer risk, many people avoid sun exposure or use sunscreen, which prevents the body from producing vitamin D. Many types of milk and dairy products, along with orange juice, are also fortified with vitamin D. Still, many of us do not get enough vitamin D and need to take a supplement. There are two forms of vitamin D dietary supplements: vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol), and it is important to understand their differences when choosing which vitamin D supplement to take.
What are the main differences between vitamin D and D3?
The term vitamin D is kind of a misnomer because you will not find anything labeled simply as “vitamin D” in a pharmacy vitamin aisle. Rather, your choices will be vitamin D2 (What is vitamin D2?) or vitamin D3 (What is vitamin D3?). Generally, when one mentions vitamin D, the implied selection is vitamin D2. For the purpose of this article, when vitamin D is mentioned, it will refer to vitamin D2. The names can be confusing because patients often go into the pharmacy looking for vitamin D and are surprised that there is a D2 and a D3.
Vitamin D (D2) comes from plant sources, such as wild mushrooms, and fortified foods, such as milk or cereal products. Its strength is typically measured in international units, which is abbreviated as “IU” on labeling. The 50,000 IU capsules are prescription only, while lower strengths are available over the counter. Vitamin D is less expensive to produce and therefore is the form most commonly found in fortified food products.
Vitamin D3 mainly comes from animal sources such as fish oil, fatty fish, liver, and egg yolks. When your skin is exposed to sunlight, it produces vitamin D3. For this reason, it is sometimes referred to as the sunshine vitamin. Its strength is also measured in international units. All forms of vitamin D3 are available over-the-counter.
| Main differences between vitamin D and D3 | ||
|---|---|---|
| Vitamin D2 | Vitamin D3 | |
| Drug class | Vitamin D Analog | Vitamin D Analog |
| Brand/generic status | Brand and generic available | Brand and generic available |
| What is the generic name?
Or |
Ergocalciferol or vitamin D2 Drisdol, Calcidol, Calciferol |
Cholecalciferol, vitamin D, or vitamin D3 Decara, Dialyvite D3 Max |
| What form(s) does the drug come in? | Oral tablets and capsules, oral liquid solution | Oral tablets and capsules, oral liquid solution, sublingual liquid solution |
| What is the standard dosage? | 1,000 IU to 2,000 IU daily for vitamin D supplementation | 1,000 IU to 2,000 IU daily for vitamin D supplementation |
| How long is the typical treatment? | Indefinite | Indefinite |
| Who typically uses the medication? | Infants, children, adolescents, and adults | Infants, children, adolescents, and adults |
Similarities between vitamin D and D3
Vitamin D and D3 are metabolized to the active metabolite form, calcitriol. From calcitriol comes the important end results of a healthy level of vitamin D in your body. Calcitriol promotes renal absorption of calcium, increases intestinal absorption of both calcium and phosphorus, and increases the mobilization of calcium from bone to plasma. Calcitriol has even been shown to inhibit cancer cell growth. Ultimately both vitamin D and D3 provide your body with the critical metabolite, calcitriol.
Conditions treated by vitamin D and D3
Vitamin D2, as a prescription, is used to treat hypoparathyroidism (decreased parathyroid hormone secretion), vitamin D resistant rickets, and hypophosphatemia (low levels of phosphorus in the blood). It is commonly used for vitamin D insufficiency in its prescription and over-the-counter formulations. The FDA does not approve treatment claims for over-the-counter vitamin supplements. Therefore, even though this use is very common, it is considered off-label.
All forms of vitamin D3 supplements are available over the counter and therefore are not FDA approved to make treatment claims. However, vitamin D3 is commonly used off-label to treat hypoparathyroidism and vitamin D deficiency, as well as for osteoporosis prevention.
| Conditions treated by vitamin D and D3 | ||
|---|---|---|
| Condition | Vitamin D2 | Vitamin D3 |
| Hypoparathyroidism | Yes | Off-label |
| Refractory rickets | Yes | Off-label |
| Hypophosphatemia | Yes | Off-label |
| Dietary supplementation | Yes | Yes |
| Vitamin D insufficiency/deficiency | Off-label | Off-label |
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Is vitamin D or D3 more effective?
Vitamin D2 and D3 are absorbed into the bloodstream where they are metabolized by the liver into 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3, otherwise collectively known as 25D or calcifediol. Calcifediol is the vitamin D complex circulating in your blood, and its levels directly reflect your body’s stores of vitamin D. Calcifediol is commonly referred to as the active form of vitamin D. When your healthcare provider orders lab tests to check your vitamin D levels, they are measuring your calcifediol (25D) levels. Calcifediol is the precursor to calcitriol, the ultimate active metabolite of vitamins D and D3.
There have been several studies comparing whether supplementation with vitamin D2 or D3 produces a higher blood level of calcifediol. A study published by the National Institutes of Health was conducted on older adults, post-menopausal women who had been identified as vitamin D deficient. It compared the effects of receiving a single high dose of vitamin D2 or vitamin D3 on calcifediol levels. The study concluded that vitamin D3 produced about twice the amount of circulating calcifediol in this patient population versus that of vitamin D2.
In a separate clinical trial comparing a 10-week regimen of twice weekly 50,000 IU dosing of both vitamin D2 and vitamin D3 in demographically matched groups, vitamin D3 was also found to be superior in producing higher levels of 25D, or calcifediol.
In terms of the lab tests that measure vitamin D levels, your healthcare provider may evaluate total 25D, free 25D, or both. Controversy remains on which lab test is the best measure of your body’s vitamin D stores, but these studies showed that vitamin D3 was superior in raising both levels.
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Coverage and cost comparison of vitamin D vs. D3
Vitamin D2 in prescription form is commonly covered by most commercial and Medicare insurance plans. The over-the-counter formulations are typically not covered by commercial or Medicare insurance plans. The price can vary greatly depending on dosage. The average cost of the 50,000 IU dose for 12 weeks of therapy is $54. With a coupon from SingleCare, this price drops to as low as $2.
Vitamin D3 is available over-the-counter and therefore is typically not covered by insurance plans. The price varies depending on the dose. D3 can cost as much as $50 per month, but if your healthcare provider prescribes the medication you can get it for as low as $8 with a SingleCare discount coupon.
| Vitamin D | Vitamin D3 | |
| Typically covered by insurance? | Yes, at prescription dosing | No |
| Typically covered by Medicare? | Yes, at prescription dosing | No |
| Standard dosage | 12, 50,000 IU capsules | 12, 50,000 IU capsules |
| Typical Medicare copay | <$10 depending on plan | n/a |
| SingleCare cost | $2-$22 | $8+ |
Common side effects of vitamin D vs. D3
There are no common side effects to therapy with either vitamin D2 or D3. Side effects related to vitamin D result from hypervitaminosis D. This extremely rare condition occurs when you take in too much vitamin D. This is sometimes seen in patients who take megadoses of vitamin D, leading to vitamin D toxicity. The result is a build-up of dangerously high levels of calcium in the blood, which can lead to nausea, vomiting, constipation, and frequent urination. If left untreated, irreversible renal failure and calcification of organs and soft tissues can occur.
The following table lists side effects related to hypervitaminosis D, not normal vitamin D supplementation. More information on vitamin D toxicity may be obtained from your healthcare provider, as this may not be a complete list.
| Common side effects of vitamin D and D3 | ||||
|---|---|---|---|---|
| Vitamin D2 | Vitamin D3 | |||
| Side Effect | Applicable? | Frequency | Applicable? | Frequency |
| Nausea | Yes | Rare | Yes | Rare |
| Vomiting | Yes | Rare | Yes | Rare |
| Constipation | Yes | Rare | Yes | Rare |
| Polyuria | Yes | Rare | Yes | Rare |
| Nocturia | Yes | Rare | Yes | Rare |
| Renal failure | Yes | Rare | Yes | Rare |
| Organ calcification | Yes | Rare | Yes | Rare |
| Soft tissue calcification | Yes | Rare | Yes | Rare |
| Anemia | Yes | Rare | Yes | Rare |
| Weight loss | Yes | Rare | Yes | Rare |
| Bone demineralization | Yes | Rare | Yes | Rare |
Source: DailyMed
Drug interactions of vitamin D vs. D3
Vitamin D2 and D3 each are metabolized by the liver to 25D, and therefore the potential drug interactions are similar for both forms. Vitamin D may increase the serum levels of aluminum when taken with aluminum hydroxide, a common antacid, and therefore the combination should be avoided. Thiazide diuretics, such as hydrochlorothiazide, may increase the chance of vitamin D raising calcium levels in the blood to a dangerously high level. Patients on both thiazide diuretics and vitamin D supplementation should be monitored for this effect by their healthcare provider. Some drugs may decrease the absorption and effectiveness of your vitamin D supplement. Bile-acid sequestrants, such as cholestyramine, are an example of a drug that will impair vitamin D absorption. Vitamin D and cholestyramine should not be administered at the same time.
The following table may not be a complete list of drug interactions. Please consult your pharmacist or healthcare provider for more information and a complete list of interactions.
| Drug | Drug Class | Vitamin D2 | Vitamin D3 |
| Aluminum hydroxide | Antacid | Yes | Yes |
| Cholestyramine | Bile-acid sequestrant | Yes | Yes |
| Danazol | Hormone | Yes | Yes |
| Erdafitinib | FGFR kinase inhibitor | Yes | Yes |
| Mineral oil | Laxative | Yes | Yes |
| Orlistat | Lipase inhibitor | Yes | Yes |
| Sucralfate | Mucosal coating agent | Yes | Yes |
| Chlorthalidone Hydrochlorothiazide Indapamide Metolazone |
Thiazide diuretic | Yes | Yes |
Warnings of vitamin D and D3
Vitamin D toxicity may occur with excessively high doses. Symptoms could include nausea, vomiting, loss of appetite, constipation, dehydration, fatigue, and confusion. Since vitamin D is a fat-soluble drug, the effects of vitamin D therapy can last 2 months or more after therapy is discontinued. It is also important to know the vitamin D content of other supplements you may be taking, such as a daily multivitamin. You should not take high doses of vitamin D supplements without your healthcare provider’s instruction.
Frequently asked questions about vitamin D vs. D3
What is vitamin D (D2)?
Vitamin D (D2—ergocalciferol) is a vitamin D supplement available in both prescription and over-the-counter formulations. It is available in oral tablets, capsules, and an oral solution. Vitamin D2 comes from plant sources and is the most common form of vitamin D found in fortified foods.
What is vitamin D3?
Vitamin D3 (cholecalciferol) is an over-the-counter vitamin D supplement available in a variety of strengths. It is available in oral tablets, capsules, and oral and sublingual solutions.
Vitamin D3 comes from animal sources such as fish oil, fatty fish, liver, or egg yolks.
Are vitamin D or D3 the same?
When we refer to vitamin D, we are talking about Vitamin D2. Vitamin D2 and D3 are both widely used vitamin D supplements but are not the same. Vitamin D2 is ergocalciferol and comes from plant-based sources. Vitamin D3 is cholecalciferol and comes from animal-based sources. Both supplements are processed in the body by the liver to 25-hydroxyvitamin D, though vitamin D3 is thought to provide higher levels of 25D. Some formulations of vitamin D2 are prescription only, while all formulations of vitamin D3 are over-the-counter.
Is vitamin D or D3 better?
Vitamin D and D3 are each processed in the body by the liver to 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3, respectively. Studies have shown that taking vitamin D3 leads to higher 25D levels, leading to a higher contribution to the body’s vitamin D stores.
Can I use vitamin D or D3 while pregnant?
Vitamin D and vitamin D3 are safe to take when pregnant and monitored by a healthcare provider. Your healthcare provider may recommend a daily supplement dose and should monitor for signs of vitamin D toxicity, which is rare.
Can I use vitamin D or D3 with alcohol?
Vitamin D and vitamin D3 are safe to take if you consume alcohol. Both substances are metabolized primarily by the liver, so liver function should be monitored by a healthcare professional.
Should I take vitamin D or D3?
Vitamin D (D2) and vitamin D3 are both effective vitamin D supplements. Vitamin D2 is approved for treating hypoparathyroidism, vitamin D resistant rickets, and hypophosphatemia. Both supplements are commonly used for vitamin D supplementation.
Studies have shown that vitamin D3 supplements may be superior in raising the body’s vitamin D stores. There are many health benefits to vitamin D supplementation, but your healthcare provider should use lab tests to recommend the amount of vitamin D you should take and which form.
What is vitamin D3 good for?
Vitamin D3 is most commonly used as a dietary supplement of vitamin D. It aids in the absorption of calcium and may be helpful in the prevention of osteoporosis and osteomalacia.
Why do healthcare providers prescribe vitamin D2 instead of D3?
Your healthcare provider may determine your vitamin D recommendation based on lab work. Some health professionals may perceive that vitamin D2 is more effective because it is available by prescription only, even though studies have shown this is not necessarily true. Vitamin D2 may also be a lower cost to the patient, especially when covered in part or full by their insurance.
Does vitamin D3 give you energy?
Increasing vitamin D intake is thought to improve energy. A clinical trial was done examining fatigue levels in patients who were identified as vitamin D deficient. These patients were given vitamin D3 supplementation to increase blood levels of vitamin D, and the results showed a significant improvement in fatigue levels. Scientists have shown this may be due to vitamin D’s effect at the cellular level, where it augments mitochondrial oxidative phosphorylation in skeletal muscle. This decreases muscle fatigue.
Should seniors take vitamin D or Vitamin D3?
Yes, vitamin D is an important vitamin for the senior population as it supports immune function and plays an essential role in calcium absorption. Vitamin D is one of several vital vitamins for seniors. The recommendations for supplemental dosing increase with age, so you should check with your healthcare provider to get the recommended dose for your age and health status
Can I take vitamin D3 every day? And how much vitamin D should I take?
Yes, you can take daily vitamin D supplements. Some dosages are designed for once-weekly or once-monthly dosing, so it is important to go over this with your healthcare professional. Many Americans are vitamin D deficient, but should we all be taking the same amount? The answer is no. The appropriate dose for your supplementation will depend on your health status, sun exposure, whether or not you are pregnant, and age, just to name a few factors. Consult your healthcare provider or pharmacist for a recommendation.