Whats the difference between d2 and d3 vitamins

Vitamin D (D2) comes mainly from plants, whereas vitamin D3 comes from animal sources. Learn about the main differences between vitamin D vs. vitamin D3

Vitamin D overview | 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 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

Similarities between vitamin D and D3

Vitamin D and D3 are both ultimately metabolized to the active metabolite form, calcitriol. From calcitriol come 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 increased 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 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.

Vitamin D and Covid

In March of 2020, the World Health Organization (WHO) declared a global pandemic in the wake of the spread of SARS-CoV-2, more commonly known as COVID-19. Due to a lack of clear treatment guidelines and a waiting period for the vaccine to be available, the focus shifted to boosting our natural immune system. Vitamin D became a key player in our fight against COVID-19. 

The COVID-19 virus promotes the release of inflammatory cytokines. This process is what causes some of the most severe respiratory symptoms, which for some have been fatal. Vitamin D is a natural defense against this process as it partially shuts down the cytokine release caused by the presence of the COVID-19 virus. Unfortunately, many Americans are vitamin D deficient, and supplementation was necessary to achieve therapeutic levels. Regimens that included vitamin D and C, as well as zinc, became commonly recommended in order to boost our ability to fight COVID-19. 

We are now more than two years into the pandemic, and we have begun to have a much deeper appreciation for the role of vitamin D levels and the severity of COVID symptoms. One meta-analysis evaluated the relationship of vitamin D levels at the time of a COVID infection and the severity of symptoms. Normal vitamin D levels are 30 nanograms per milliliter (ng/ml) of blood or higher. There was a correlation between vitamin D levels below 20 ng/ml and severe COVID symptoms. While the cases were deemed more severe, there was not a relationship to an increase in mortality based on the 21 eligible studies evaluated for this analysis.

Based on this type of knowledge, another group of researchers evaluated the use of short-term, high-dose vitamin D supplementation  in COVID patients. The SHADE study revealed that vitamin D supplementation in this fashion was linked to lower fibrinogen levels, an indicator of inflammation, as well as a higher rate of COVID positive patients subsequently testing negative for COVID.

For all of the data suggesting a link between vitamin D levels and COVID severity, there are also researchers that suggest that there is no true link between vitamin D levels and susceptibility or severity of COVID. It may take many more years to fully appreciate the complex relationship, but we do know that many Americans are vitamin D deficient. Irrespective of COVID, healthy vitamin D levels play an important role in our health and immunity. Talk with your healthcare professional to see if vitamin D supplementation is right for you.

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

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 doctor 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 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 $54. With a coupon from SingleCare, this price drops to as low as $2.

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 much as $50 per one month supply, but if your doctor 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 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 $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 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.

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 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.

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 also plays an important role in calcium absorption. Vitamin D is one of several important vitamins for seniors. The recommendations for supplemental dosing increase with increasing 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 everyday? / How much should I take?

Yes, you can take daily vitamin D supplements. There are some dosages that 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, your sun exposure, whether or not you are pregnant, and your age, just to name a few factors. Consult your physician or pharmacist for a recommendation. 

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Why do doctors prescribe vitamin D2 instead of D3?

Vitamin D supplements are available as vitamin D2 (D2) and vitamin D3 (D3). Both versions can be used to treat vitamin D deficiency, but D3 seems to be more effective than D2. Vitamin D2 is still prescribed to people with low vitamin D levels, because it's more readily available in higher doses.

Is it better to take vitamin D2 or D3?

Studies have repeatedly shown that vitamin D3 is superior at raising levels of vitamin D in the body. These findings were supported by a recent review of the evidence which found that vitamin D3 supplementation increased vitamin D levels in the body better than vitamin D2.

Do you need both vitamin D2 and D3?

Although you can safely take both vitamin D2 and D3 supplements, the effectiveness of the two forms of the vitamin differs. Experts agree that vitamin D3 is a preferable choice over D2. Not only is D3 the form that occurs naturally in the human body but it also raises blood levels of vitamin D much more effectively.

Is vitamin D2 equivalent to vitamin D3?

Vitamin D2 has been found to be either equivalent (12–14) or slightly less potent (15–18) than vitamin D3 for obtaining optimal serum 25OHD concentrations at least when given in daily dosages. However, when given intermittently vitamin D2 is clearly less potent than vitamin D3 (14, 19).