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Vitamin D vs. D3: Differences, similarities, and which is better for you

Drug overview & main differences | Conditions treated | Efficacy | Insurance coverage and cost comparison | Side effects | Drug interactions | Warnings | FAQ

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 many times, patients 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, as well as 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?
What is the brand name?
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

Conditions treated by vitamin D and D3

Vitamin D2 as a prescription is used to treat hypoparathyroidism (decreased thyroid hormone secretion), vitamin D resistant rickets, and hypophosphatemia (low levels of phosphorus in the blood). It is commonly used for vitamin D insufficiency in both 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.

Various uses of vitamin D supplementation are listed in the table below. You should always seek medical advice before beginning vitamin D supplementation.

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 doctor orders lab tests to check your vitamin D levels, they are measuring your calcifediol (25D) levels.

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 in elderly, 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 which measure vitamin D levels, your doctor may evaluate total 25D or 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 $47.99. With a coupon from SingleCare, this price drops to as low as $11.

Vitamin D3 is over-the-counter, and therefore is typically not covered by insurance plans. The price varies depending on dose. D3 can cost as $40 but if your doctor prescribes the medication you can get it for as low as $20 with a SingleCare discount coupon.

  Vitamin D2 Vitamin D3
Typically covered by insurance? Yes, at prescription dosing No
Typically covered by Medicare Part D? Yes, at prescription dosing No
Standard dosage 12, 50,000 IU capsules 12, 50,000 IU capsules
Typical Medicare Part D copay <$10 depending on plan n/a
SingleCare cost $11-$17 $20+

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 are the result of hypervitaminosis D, an extremely rare condition that occurs when you intake 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 can occur along with calcification of organs and soft tissues.

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 doctor or pharmacist, as this may not be a complete list.

  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 D2 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 which 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. Due to the fact that 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 doctor’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 and capsules, as well as 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 and capsules, as well as 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, which in turn leads 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 doctor. Your doctor may recommend a daily supplement dose and should monitor for signs of a rare vitamin D toxicity.

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 each effective vitamin D supplements. Vitamin D2 is approved in the treatment of 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 doctor 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 doctors prescribe vitamin D2 instead of D3?

Your doctor may determine your vitamin D recommendation based on lab work. Among some health professionals, there may be a perception 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.